Trial Outcomes & Findings for Effectiveness and Cost-Effectiveness of Fully-Automated Digital vs. Human Coach-Based Diabetes Prevention Programs (NCT NCT05056376)

Last Updated: 2025-12-17

Results Overview

The primary outcome was the CDC-defined diabetes risk reduction benchmark at 12 months (based on the 2021 standards), defined as at least one of the following: 1. Weight loss of ≥5%. 2. Weight loss of ≥4% combined with at least 150 weekly minutes of moderate-to-vigorous PA 3. An absolute decrease of ≥0.2 points in A1C (measured in %). The A1C endpoint was applicable only to participants with baseline A1C of 5.7% to 6.4%. Maintaining an A1C \<6.5% throughout the study was also a criterion for the primary outcome.

Recruitment status

COMPLETED

Study phase

Target enrollment

368 participants

Primary outcome timeframe

12 months

Results posted on

2025-12-17

Participant Flow

Participant milestones

Participant milestones
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.
Overall Study STARTED	183	185
Overall Study COMPLETED	151	149
Overall Study NOT COMPLETED	32	36

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effectiveness and Cost-Effectiveness of Fully-Automated Digital vs. Human Coach-Based Diabetes Prevention Programs

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) n=183 Participants Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) n=185 Participants Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.	Total n=368 Participants Total of all reporting groups
Age, Continuous	60.0 Years n=6 Participants	57.0 Years n=5 Participants	58.0 Years n=5 Participants
Sex: Female, Male Female	121 Participants n=6 Participants	139 Participants n=5 Participants	260 Participants n=5 Participants
Sex: Female, Male Male	62 Participants n=6 Participants	46 Participants n=5 Participants	108 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaskan Native	0 Participants n=6 Participants	1 Participants n=5 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	11 Participants n=6 Participants	16 Participants n=5 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	51 Participants n=6 Participants	49 Participants n=5 Participants	100 Participants n=5 Participants
Race/Ethnicity, Customized Race · White or Caucasian	114 Participants n=6 Participants	111 Participants n=5 Participants	225 Participants n=5 Participants
Race/Ethnicity, Customized Race · More than One Race	3 Participants n=6 Participants	5 Participants n=5 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	4 Participants n=6 Participants	2 Participants n=5 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Race · Declined to Answer	0 Participants n=6 Participants	1 Participants n=5 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	176 Participants n=6 Participants	167 Participants n=5 Participants	343 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	5 Participants n=6 Participants	15 Participants n=5 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Declined to Answer	1 Participants n=6 Participants	1 Participants n=5 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Unknown	1 Participants n=6 Participants	2 Participants n=5 Participants	3 Participants n=5 Participants
Marital Status Married/Partnered	120 Participants n=6 Participants	121 Participants n=5 Participants	241 Participants n=5 Participants
Marital Status Previously Married	27 Participants n=6 Participants	26 Participants n=5 Participants	53 Participants n=5 Participants
Marital Status Single/Other	36 Participants n=6 Participants	38 Participants n=5 Participants	74 Participants n=5 Participants
Educational Attainment High School or Less	23 Participants n=6 Participants	19 Participants n=5 Participants	42 Participants n=5 Participants
Educational Attainment Some College/Associate's Degree	38 Participants n=6 Participants	36 Participants n=5 Participants	74 Participants n=5 Participants
Educational Attainment Bachelor's Degree	53 Participants n=6 Participants	55 Participants n=5 Participants	108 Participants n=5 Participants
Educational Attainment Graduate/Professional Degree	69 Participants n=6 Participants	74 Participants n=5 Participants	143 Participants n=5 Participants
Educational Attainment Declined to Answer	0 Participants n=6 Participants	1 Participants n=5 Participants	1 Participants n=5 Participants
Body Mass Index (BMI)	32.2 Kg/m^2 n=6 Participants	32.5 Kg/m^2 n=5 Participants	32.3 Kg/m^2 n=5 Participants
Dyslipidemia	85 Participants n=6 Participants	86 Participants n=5 Participants	171 Participants n=5 Participants
Hypertension	82 Participants n=6 Participants	78 Participants n=5 Participants	160 Participants n=5 Participants
Back Pain	52 Participants n=6 Participants	44 Participants n=5 Participants	96 Participants n=5 Participants
Mood Disorder	39 Participants n=6 Participants	43 Participants n=5 Participants	82 Participants n=5 Participants
Osteoarthritis	39 Participants n=6 Participants	32 Participants n=5 Participants	71 Participants n=5 Participants
Asthma/COPD	31 Participants n=6 Participants	28 Participants n=5 Participants	59 Participants n=5 Participants
BMI Classification Overweight	55 Participants n=6 Participants	47 Participants n=5 Participants	102 Participants n=5 Participants
BMI Classification Class I Obesity	70 Participants n=6 Participants	57 Participants n=5 Participants	127 Participants n=5 Participants
BMI Classification Class II Obesity	33 Participants n=6 Participants	47 Participants n=5 Participants	80 Participants n=5 Participants
BMI Classification Class III Obesity	25 Participants n=6 Participants	34 Participants n=5 Participants	59 Participants n=5 Participants
A1C	5.8 % STANDARD_DEVIATION 0.3 • n=6 Participants	5.8 % STANDARD_DEVIATION 0.3 • n=5 Participants	5.8 % STANDARD_DEVIATION 0.3 • n=5 Participants
Actigraph Measured Moderate-to-Vigorous Physical Activity (MVPA)	237.0 Minutes per Week n=6 Participants	239.0 Minutes per Week n=5 Participants	237.0 Minutes per Week n=5 Participants
Actigraphy-measured MVPA <150 min/week	54 Participants n=6 Participants	65 Participants n=5 Participants	119 Participants n=5 Participants
Diet Quality Healthiest Diet (1-5)	70 Participants n=6 Participants	73 Participants n=5 Participants	143 Participants n=5 Participants
Diet Quality Moderately Healthy Diet (6-10)	50 Participants n=6 Participants	58 Participants n=5 Participants	108 Participants n=5 Participants
Diet Quality Least Healthy Diet (11-16)	63 Participants n=6 Participants	54 Participants n=5 Participants	117 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Outcome measures

Outcome measures
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) n=183 Participants Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) n=185 Participants Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.
Achievement of CDC's Benchmark for Type 2 Diabetes Risk Reduction as a Binary Outcome (Yes/no)	58 Participants	59 Participants

SECONDARY outcome

Timeframe: At 12 months

Absolute weight change (kilograms) from baseline to 12 months

Outcome measures

Outcome measures
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) n=151 Participants Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) n=149 Participants Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.
Absolute Weight Change	-1.00 Kg Interval -3.2 to 1.5	-1.30 Kg Interval -4.3 to 1.1

SECONDARY outcome

Timeframe: 12 months

The investigators will compare the cost-effectiveness of the two interventions based on lifetime horizon by constructing a Markov model with model parameters populated from the trial results as well as other published literature. The model will estimate the incremental cost-effectiveness ratio between the two interventions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 12 months

Population: Per-protocol analysis included participants with available 12-month outcome data who did not initiate prohibited medications during the trial. Change in A1C analysis was restricted to participants whose baseline A1C at randomization was between 5.7% and 6.4%.

Change in HbA1C (percentage points) from baseline to 12 months (among participants with baseline HbA1C of 5.7% - 6.4% who completed the 12-month study visit).

Outcome measures

Outcome measures
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) n=106 Participants Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) n=103 Participants Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.
Change in Hemoglobin A1C	0.0 Percentage of Total Hemoglobin Interval -0.2 to 0.1	-0.1 Percentage of Total Hemoglobin Interval -0.2 to 0.1

SECONDARY outcome

Timeframe: At 12 months

Percentage change in weight from baseline to 12 months

Outcome measures

Outcome measures
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) n=151 Participants Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) n=149 Participants Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.
Percentage Change in Weight	-1.03 percentage change Interval -3.73 to 1.46	-1.43 percentage change Interval -4.03 to 1.14

SECONDARY outcome

Timeframe: At 12 months

Average minutes/week of physical activity assessed using blinded Actigraphy (monthly serial consecutive 7-days wear period). If the participant did not wear their monitor for at least 5 of their 7 assigned days, they were considered noncompliant. In this case, the participant was assigned 0 minutes for physical activity for that week.To obtain the average MVPA minutes per week across the study period, the total MVPA minutes per week from all valid wear periods were summed and divided by the number of available wear periods (maximum of 11 post-baseline visits). Specifically, activity intensity was classified as MVPA if the vector magnitude of accelerometer counts per minute was equal to or greater than 3941 (Montoye's cut point).

Outcome measures

Outcome measures
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) n=151 Participants Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) n=149 Participants Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.
Mean Weekly Moderate-to-vigorous Physical Activity (MVPA)	210.5 Minutes per Week Interval 134.5 to 344.0	174.4 Minutes per Week Interval 73.9 to 321.3

SECONDARY outcome

Timeframe: At either 6 or 12 months

Number of individuals who had an AIC in the diabetes range (A1C ≥6.5%) at the 6-month or 12-month timepoint.

Outcome measures

Outcome measures
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) n=151 Participants Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) n=149 Participants Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.
Incidence of Diabetes-range A1C	8 Participants	7 Participants

SECONDARY outcome

Timeframe: 12 months

To compare the acceptability of the two interventions (satisfaction, utility, interest, motivation, user experience, etc.) using the 32-item acceptability questionnaire. Scoring: Sum up all responses to questions 1-31, divide by 155 and multiply by 100 to calculate percentage score out of 100%. The range of possible scores is 20% (lowest acceptability) to 100% (highest possible acceptability).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months and 12 months

To evaluate the correlation between self-reported PA data collected using different methods: * Data collected and reported by hDPPs * Self-reported PA data collected by study team obtained at 1-month intervals * Objectively measured PA data (Actigraphy) obtained at 1-month intervals

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 12 months

Program initiators were defined as participants who attended at least one in-person session (Human-DPP) or registered and used the Sweetch app (AI-DPP).

Outcome measures

Outcome measures
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) n=183 Participants Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) n=185 Participants Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.
Program Initiation Rate	171 Participants	153 Participants

SECONDARY outcome

Timeframe: At 12 months

Program completers attended ≥8 sessions in months 1-6 and spanned ≥9 months (Human-DPP), or engaged with the app for ≥8 weeks during months 1-6 with a span of ≥9 months between initiation and last engagement (AI-DPP).

Outcome measures

Outcome measures
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) n=183 Participants Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) n=185 Participants Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.
Program Completion Rate	117 Participants	93 Participants

Adverse Events

Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP)

Serious events: 36 serious events

Other events: 10 other events

Deaths: 0 deaths

Human Coach-Based Diabetes Prevention Program (Human-DPP)

Serious events: 6 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Nestoras Mathioudakis, MD MHS

Johns Hopkins University, School of Medicine

Phone: 667-306-8085

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) n=183 participants at risk Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) n=185 participants at risk Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.
Cardiac disorders Atrioventricular block	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Musculoskeletal and connective tissue disorders Fracture of ankle	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Gastrointestinal disorders Appendicitis	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast malignant tumors	1.1% 2/183 • Number of events 2 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.54% 1/185 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Infections and infestations COVID-19	2.2% 4/183 • Number of events 4 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.54% 1/185 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Eye disorders Phacoemulsification	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Cardiac disorders Chest Pain	1.6% 3/183 • Number of events 3 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Endocrine disorders Diabetes mellitus	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Ear and labyrinth disorders Otalgia	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Renal and urinary disorders Flank pain	1.1% 2/183 • Number of events 3 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Nervous system disorders Foot drop	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Surgical and medical procedures Foot surgery	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Surgical and medical procedures Hammer toe surgery	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Nervous system disorders Headache	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Gastrointestinal disorders Diverticulum intestinal hemorrhagic	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Musculoskeletal and connective tissue disorders Hip fracture	0.00% 0/183 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.54% 1/185 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Musculoskeletal and connective tissue disorders Hip pain	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Musculoskeletal and connective tissue disorders Knee Pain	0.00% 0/183 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.54% 1/185 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Musculoskeletal and connective tissue disorders Meniscus injury	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Renal and urinary disorders Nephrolithiasis	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Gastrointestinal disorders Pancreatitis	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Nervous system disorders Parkinson's disease	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Hepatobiliary disorders Gallbladder perforation	0.00% 0/183 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.54% 1/185 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer stage 1	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Gastrointestinal disorders Rectal hemorrhage	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Eye disorders Retinal detachment	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Musculoskeletal and connective tissue disorders Rotator cuff tear	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Surgical and medical procedures Stem cell transplant	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Cardiac disorders Supraventricular tachycardia	0.00% 0/183 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.54% 1/185 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Nervous system disorders Syncope	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Vascular disorders Giant cell arteritis	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Nervous system disorders Vertigo	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Musculoskeletal and connective tissue disorders Wrist operation NOS	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.

Other adverse events
Measure	Artificial Intelligence-Based Diabetes Prevention Program (AI-DPP) n=183 participants at risk Participants in the AI-DPP group were referred to Sweetch Health, Ltd, and received a digital health kit from within 8-12 days post-randomization, which included a Bluetooth scale and Sweetch app registration instructions. The app delivered personalized push notifications for weight management, physical activity (PA), and nutrition, informed by both actively collected data (e.g., weight measurements, meal logging) and passively collected data (e.g., geolocation, accelerometry). PA was tracked via smartphone or wearable devices, meals were logged through a food library or photo-based detection, and weight was recorded either automatically through the scale or manually. The AI used in the Sweetch intervention consisted of a reinforcement learning algorithm that did not employ large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement. The app also delivered location- and goal-specific nutrition education and included gamification elements and educational resources.	Human Coach-Based Diabetes Prevention Program (Human-DPP) n=185 participants at risk Participants in the Human-DPP group were referred to one of four 12-month accredited lifestyle change programs: Brancati Center and University of Maryland Medical Center (Baltimore, MD), Pottstown Medical Specialists and Montgomery County DPP (Reading, PA). All four participating DPPs had full plus recognition status from the CDC. Due to COVID-19, all sessions transitioned to synchronous distance learning (i.e., group video conferences). Trained lifestyle coaches led sessions based on the CDC's PreventT2 curriculum, covering healthy eating, food tracking, PA, behavior modification, and long-term weight management, with an initial core phase (16 weekly sessions) and a remaining core maintenance phase (bi-weekly to monthly sessions) to complete the 12-month intervention. Of note, our study participants joined DPP cohorts that were comprised of standard enrollees who were not participants in our trial.
Psychiatric disorders Anxiety	0.00% 0/183 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.54% 1/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Infections and infestations COVID-19	1.1% 2/183 • Number of events 2 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.54% 1/185 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Injury, poisoning and procedural complications Concussion	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Injury, poisoning and procedural complications Foreign body in ear	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Injury, poisoning and procedural complications Radius fracture	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Psychiatric disorders Generalized anxiety disorder	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Infections and infestations Influenza	0.00% 0/183 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.54% 1/185 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Nervous system disorders Migraine	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Renal and urinary disorders Kidney stone	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Musculoskeletal and connective tissue disorders Osteopenia	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Nervous system disorders Neuropathy peripheral	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Infections and infestations Sinusitis	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Gastrointestinal disorders Diarrhoea	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Infections and infestations Diverticulitis	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Injury, poisoning and procedural complications Skin laceration	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.
Gastrointestinal disorders Vomiting	0.55% 1/183 • Number of events 1 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.	0.00% 0/185 • From enrollment until the end of follow-up (12-month visit) Grade 1: mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; no intervention required;Grade 2: moderate, requiring minimal or local intervention;Grade 3: severe or medically significant but not immediately life-threatening, necessitating hospitalization or prolongation of hospitalization; disabling; limits self-care activities of daily living;Grade 4: life-threatening consequences requiring urgent intervention;Grade 5: death related to the adverse event.