Trial Outcomes & Findings for A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone (NCT NCT03954834)

Last Updated: 2021-10-20

Results Overview

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Prior Use of oral antihyperglycemic medication (OAM) (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

478 participants

Primary outcome timeframe

Baseline, Week 40

Results posted on

2021-10-20

Participant Flow

Participant milestones

Participant milestones
Measure	5 mg Tirzepatide Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo Participants received placebo as subcutaneous injection once a week.
Overall Study STARTED	121	121	121	115
Overall Study Received at Least One Dose of Study Drug	121	121	121	115
Overall Study COMPLETED	114	112	103	99
Overall Study NOT COMPLETED	7	9	18	16

Reasons for withdrawal

Reasons for withdrawal
Measure	5 mg Tirzepatide Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo Participants received placebo as subcutaneous injection once a week.
Overall Study Adverse Event	1	3	1	1
Overall Study Death	0	0	0	1
Overall Study Physician Decision	0	1	0	2
Overall Study Protocol Violation	1	0	0	1
Overall Study Withdrawal by Subject	2	3	13	6
Overall Study Participant left the country	0	0	1	0
Overall Study Lost to Follow-up	3	2	3	5

Baseline Characteristics

A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5 mg Tirzepatide n=121 Participants Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide n=121 Participants Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide n=121 Participants Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo n=115 Participants Participants received placebo as subcutaneous injection once a week.	Total n=478 Participants Total of all reporting groups
Age, Continuous	54.10 years STANDARD_DEVIATION 11.88 • n=5 Participants	55.80 years STANDARD_DEVIATION 10.35 • n=7 Participants	52.90 years STANDARD_DEVIATION 12.34 • n=5 Participants	53.60 years STANDARD_DEVIATION 12.79 • n=4 Participants	54.10 years STANDARD_DEVIATION 11.88 • n=21 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	49 Participants n=7 Participants	58 Participants n=5 Participants	59 Participants n=4 Participants	231 Participants n=21 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	72 Participants n=7 Participants	63 Participants n=5 Participants	56 Participants n=4 Participants	247 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	50 Participants n=5 Participants	54 Participants n=7 Participants	55 Participants n=5 Participants	48 Participants n=4 Participants	207 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants	49 Participants n=7 Participants	42 Participants n=5 Participants	45 Participants n=4 Participants	184 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	23 Participants n=5 Participants	18 Participants n=7 Participants	24 Participants n=5 Participants	22 Participants n=4 Participants	87 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	31 Participants n=5 Participants	31 Participants n=7 Participants	30 Participants n=5 Participants	26 Participants n=4 Participants	118 Participants n=21 Participants
Race (NIH/OMB) Asian	45 Participants n=5 Participants	43 Participants n=7 Participants	42 Participants n=5 Participants	38 Participants n=4 Participants	168 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	22 Participants n=21 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants	43 Participants n=7 Participants	43 Participants n=5 Participants	46 Participants n=4 Participants	170 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment India	18 Participants n=5 Participants	20 Participants n=7 Participants	18 Participants n=5 Participants	17 Participants n=4 Participants	73 Participants n=21 Participants
Region of Enrollment Japan	23 Participants n=5 Participants	22 Participants n=7 Participants	23 Participants n=5 Participants	21 Participants n=4 Participants	89 Participants n=21 Participants
Region of Enrollment Mexico	42 Participants n=5 Participants	40 Participants n=7 Participants	42 Participants n=5 Participants	40 Participants n=4 Participants	164 Participants n=21 Participants
Region of Enrollment Puerto Rico	2 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	1 Participants n=4 Participants	12 Participants n=21 Participants
Region of Enrollment United States	36 Participants n=5 Participants	35 Participants n=7 Participants	33 Participants n=5 Participants	36 Participants n=4 Participants	140 Participants n=21 Participants
Hemoglobin A1c	7.97 Percentage of HbA1c STANDARD_DEVIATION 0.841 • n=5 Participants	7.90 Percentage of HbA1c STANDARD_DEVIATION 0.78 • n=7 Participants	7.85 Percentage of HbA1c STANDARD_DEVIATION 1.02 • n=5 Participants	8.05 Percentage of HbA1c STANDARD_DEVIATION 0.80 • n=4 Participants	7.94 Percentage of HbA1c STANDARD_DEVIATION 0.87 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 40

Population: All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.

Outcome measures

Outcome measures
Measure	5 mg Tirzepatide n=121 Participants Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide n=118 Participants Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide n=116 Participants Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo n=112 Participants Participants received placebo as subcutaneous injection once a week.
Change From Baseline in Hemoglobin A1c (HbA1c)	-1.87 Percentage of HbA1c Standard Error 0.094	-1.89 Percentage of HbA1c Standard Error 0.096	-2.07 Percentage of HbA1c Standard Error 0.098	0.04 Percentage of HbA1c Standard Error 0.105

SECONDARY outcome

Timeframe: Baseline, Week 40

Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Outcome measures

Outcome measures
Measure	5 mg Tirzepatide n=121 Participants Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide n=118 Participants Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide n=116 Participants Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo n=112 Participants Participants received placebo as subcutaneous injection once a week.
Change From Baseline in Body Weight	-7.0 Kilograms (kg) Standard Error 0.52	-7.8 Kilograms (kg) Standard Error 0.53	-9.5 Kilograms (kg) Standard Error 0.54	-0.7 Kilograms (kg) Standard Error 0.57

SECONDARY outcome

Timeframe: Week 40

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Outcome measures

Outcome measures
Measure	5 mg Tirzepatide n=121 Participants Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide n=118 Participants Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide n=116 Participants Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo n=112 Participants Participants received placebo as subcutaneous injection once a week.
Percentage of Participants With HbA1c Target Value of <7%	86.78 Percentage of participants	91.53 Percentage of participants	87.93 Percentage of participants	19.64 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 40

Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Outcome measures

Outcome measures
Measure	5 mg Tirzepatide n=121 Participants Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide n=118 Participants Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide n=116 Participants Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo n=112 Participants Participants received placebo as subcutaneous injection once a week.
Change From Baseline in Fasting Serum Glucose	-43.6 milligram per Deciliter (mg/dL) Standard Error 3.40	-45.9 milligram per Deciliter (mg/dL) Standard Error 3.45	-49.3 milligram per Deciliter (mg/dL) Standard Error 3.62	12.9 milligram per Deciliter (mg/dL) Standard Error 4.00

SECONDARY outcome

Timeframe: Week 40

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Outcome measures

Outcome measures
Measure	5 mg Tirzepatide n=121 Participants Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide n=118 Participants Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide n=116 Participants Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo n=112 Participants Participants received placebo as subcutaneous injection once a week.
Percentage of Participants With HbA1c Target Value of <5.7%	33.88 Percentage of participants	30.51 Percentage of participants	51.72 Percentage of participants	0.89 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 40

The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Outcome measures

Outcome measures
Measure	5 mg Tirzepatide n=115 Participants Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide n=111 Participants Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide n=108 Participants Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo n=101 Participants Participants received placebo as subcutaneous injection once a week.
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values Morning Premeal - Fasting	-46.9 mg/dL Standard Error 2.09	-47.9 mg/dL Standard Error 2.11	-45.7 mg/dL Standard Error 2.23	-9.2 mg/dL Standard Error 2.53
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values Morning 2-hour Postmeal	-69.5 mg/dL Standard Error 3.41	-61.4 mg/dL Standard Error 3.44	-68.9 mg/dL Standard Error 3.66	-11.6 mg/dL Standard Error 4.12
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values Midday Premeal	-43.5 mg/dL Standard Error 2.80	-42.5 mg/dL Standard Error 2.82	-42.7 mg/dL Standard Error 3.00	-2.6 mg/dL Standard Error 3.42
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values Midday 2-hour Postmeal	-64.2 mg/dL Standard Error 3.60	-60.0 mg/dL Standard Error 3.63	-63.4 mg/dL Standard Error 3.84	-12.7 mg/dL Standard Error 4.33
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values Evening Premeal	-44.8 mg/dL Standard Error 2.80	-45.1 mg/dL Standard Error 2.82	-42.3 mg/dL Standard Error 3.02	-5.8 mg/dL Standard Error 3.38
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values Evening 2-hour Postmeal	-61.9 mg/dL Standard Error 3.76	-62.8 mg/dL Standard Error 3.81	-63.5 mg/dL Standard Error 4.03	-10.3 mg/dL Standard Error 4.52
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values Bedtime	-57.0 mg/dL Standard Error 3.49	-59.8 mg/dL Standard Error 3.52	-60.8 mg/dL Standard Error 3.66	-9.1 mg/dL Standard Error 4.10

SECONDARY outcome

Timeframe: Week 40

Percentage of Participants who Achieved Weight Loss ≥5%.

Outcome measures

Outcome measures
Measure	5 mg Tirzepatide n=121 Participants Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide n=118 Participants Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide n=116 Participants Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo n=112 Participants Participants received placebo as subcutaneous injection once a week.
Percentage of Participants Who Achieved Weight Loss ≥5%	66.94 Percentage of participants	77.97 Percentage of participants	76.72 Percentage of participants	14.29 Percentage of participants

SECONDARY outcome

Timeframe: Baseline through end of safety follow-up (up to week 44)

Population: All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value.

The hypoglycemia events were defined by participant reported events with blood glucose \<54mg/dL) (\<3.0 mmol/L\] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment, with log (exposure in days/365.25) as an offset variable.

Outcome measures

Outcome measures
Measure	5 mg Tirzepatide n=121 Participants Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide n=119 Participants Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide n=120 Participants Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo n=115 Participants Participants received placebo as subcutaneous injection once a week.
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia	0.02 Episodes/participant/365.25 days Standard Error 0.002	0.02 Episodes/participant/365.25 days Standard Error 0.002	0.02 Episodes/participant/365.25 days Standard Error 0.002	0.04 Episodes/participant/365.25 days Standard Error 0.028

SECONDARY outcome

Timeframe: Week 7, 15 and 23

Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.

Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide. AUC is a combined measure obtained from Week 7, 15 and 23, and a single averaged measure of AUC was reported.

Outcome measures

Outcome measures
Measure	5 mg Tirzepatide n=121 Participants Participants received 5 mg of tirzepatide as subcutaneous injection once a week.	10 mg Tirzepatide n=118 Participants Participants received 10mg of tirzepatide as subcutaneous injection once a week.	15 mg Tirzepatide n=120 Participants Participants received 15mg of tirzepatide as subcutaneous injection once a week.	Placebo Participants received placebo as subcutaneous injection once a week.
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide	86900 nanogramshours per milliliter (hng/mL) Geometric Coefficient of Variation 25.4	171000 nanogramshours per milliliter (hng/mL) Geometric Coefficient of Variation 26.2	252000 nanogramshours per milliliter (hng/mL) Geometric Coefficient of Variation 23.3	—

Adverse Events

5 mg Tirzepatide

Serious events: 5 serious events

Other events: 50 other events

Deaths: 0 deaths

10 mg Tirzepatide

Serious events: 2 serious events

Other events: 55 other events

Deaths: 0 deaths

15 mg Tirzepatide

Serious events: 1 serious events

Other events: 53 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 54 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	5 mg Tirzepatide n=121 participants at risk Participants received 5 mg of Tirzepatide as subcutaneous injection, once weekly.	10 mg Tirzepatide n=121 participants at risk Participants received 10 mg of Tirzepatide as subcutaneous injection, once weekly.	15 mg Tirzepatide n=121 participants at risk Participants received 15 mg of Tirzepatide as subcutaneous injection, once weekly.	Placebo n=115 participants at risk Participants received placebo as subcutaneous injection, once weekly.
Cardiac disorders Acute myocardial infarction	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.87% 1/115 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.87% 1/115 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Cardiac disorders Supraventricular tachycardia	0.83% 1/121 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/115 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis ischaemic	0.83% 1/121 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/115 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Clostridium difficile infection	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.83% 1/121 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/115 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.83% 1/121 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/115 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.83% 1/121 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/115 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.83% 1/121 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/115 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.87% 1/115 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Nervous system disorders Syncope	0.83% 1/121 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/115 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.83% 1/121 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/115 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.83% 1/121 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/115 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Vascular disorders Peripheral arterial occlusive disease	0.83% 1/121 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/115 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.

Other adverse events

Other adverse events
Measure	5 mg Tirzepatide n=121 participants at risk Participants received 5 mg of Tirzepatide as subcutaneous injection, once weekly.	10 mg Tirzepatide n=121 participants at risk Participants received 10 mg of Tirzepatide as subcutaneous injection, once weekly.	15 mg Tirzepatide n=121 participants at risk Participants received 15 mg of Tirzepatide as subcutaneous injection, once weekly.	Placebo n=115 participants at risk Participants received placebo as subcutaneous injection, once weekly.
Gastrointestinal disorders Constipation	5.8% 7/121 • Number of events 11 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	5.0% 6/121 • Number of events 6 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	6.6% 8/121 • Number of events 9 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.87% 1/115 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	11.6% 14/121 • Number of events 21 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	14.0% 17/121 • Number of events 19 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	11.6% 14/121 • Number of events 20 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	7.8% 9/115 • Number of events 15 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	9.1% 11/121 • Number of events 15 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	6.6% 8/121 • Number of events 12 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	5.8% 7/121 • Number of events 7 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	3.5% 4/115 • Number of events 4 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	11.6% 14/121 • Number of events 31 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	13.2% 16/121 • Number of events 82 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	18.2% 22/121 • Number of events 50 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	6.1% 7/115 • Number of events 8 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	3.3% 4/121 • Number of events 6 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	2.5% 3/121 • Number of events 3 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	5.8% 7/121 • Number of events 9 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	1.7% 2/115 • Number of events 3 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Influenza	5.8% 7/121 • Number of events 7 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	2.5% 3/121 • Number of events 3 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/121 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	1.7% 2/115 • Number of events 2 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	5.8% 7/121 • Number of events 7 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	6.6% 8/121 • Number of events 13 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	6.6% 8/121 • Number of events 8 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	8.7% 10/115 • Number of events 11 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	4.1% 5/121 • Number of events 5 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	6.6% 8/121 • Number of events 9 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	8.3% 10/121 • Number of events 10 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	0.87% 1/115 • Number of events 1 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	3.3% 4/121 • Number of events 4 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	4.1% 5/121 • Number of events 7 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	2.5% 3/121 • Number of events 3 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	27.0% 31/115 • Number of events 31 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	4.1% 5/121 • Number of events 9 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	3.3% 4/121 • Number of events 7 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	4.1% 5/121 • Number of events 8 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.	7.8% 9/115 • Number of events 12 • Baseline to end of Safety follow-up (up to 44 weeks) All randomized participants who received at least one dose of study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60