Trial Outcomes & Findings for Long Term Comparative Effectiveness of Once Weekly Semaglutide Versus Standard of Care in a Real World Adult US Population With Type 2 Diabetes - a Randomized Pragmatic Trial (NCT NCT03596450)

Last Updated: 2024-07-03

Results Overview

Number of participants who achieved HbA1c less than 7.0 % (53 mmol/mol) at year 1 is presented. Yes: number of participants who achieved HbA1c less than 7.0 % at year 1; No: number of participants who did not achieve HbA1c less than 7.0 % at year 1.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

1278 participants

Primary outcome timeframe

At year 1

Results posted on

2024-07-03

Participant Flow

The trial was conducted at 138 sites in the United States.

A total of 1,278 participants were randomized 1:1 to receive either semaglutide or standard of care (SOC).

Participant milestones

Participant milestones
Measure	Semaglutide Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Overall Study STARTED	644	634
Overall Study COMPLETED	463	447
Overall Study NOT COMPLETED	181	187

Reasons for withdrawal

Reasons for withdrawal
Measure	Semaglutide Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Overall Study Death	9	9
Overall Study Protocol Violation	18	26
Overall Study Lost to Follow-up	50	56
Overall Study Adverse Event	14	7
Overall Study Withdrawal by Subject	38	36
Overall Study Accidentally Randomized	2	0
Overall Study Other reasons	48	53
Overall Study Pregnancy	2	0

Baseline Characteristics

Gender data for one participant is missing in the Semaglutide arm.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Semaglutide n=644 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=634 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Total n=1278 Participants Total of all reporting groups
Age, Continuous	57.47 years STANDARD_DEVIATION 11.305 • n=644 Participants	57.24 years STANDARD_DEVIATION 10.982 • n=634 Participants	57.36 years STANDARD_DEVIATION 11.142 • n=1278 Participants
Sex: Female, Male Female	309 Participants n=643 Participants • Gender data for one participant is missing in the Semaglutide arm.	276 Participants n=634 Participants • Gender data for one participant is missing in the Semaglutide arm.	585 Participants n=1277 Participants • Gender data for one participant is missing in the Semaglutide arm.
Sex: Female, Male Male	334 Participants n=643 Participants • Gender data for one participant is missing in the Semaglutide arm.	358 Participants n=634 Participants • Gender data for one participant is missing in the Semaglutide arm.	692 Participants n=1277 Participants • Gender data for one participant is missing in the Semaglutide arm.
Ethnicity (NIH/OMB) Hispanic or Latino	57 Participants n=644 Participants	57 Participants n=634 Participants	114 Participants n=1278 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	586 Participants n=644 Participants	577 Participants n=634 Participants	1163 Participants n=1278 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=644 Participants	0 Participants n=634 Participants	1 Participants n=1278 Participants
Race/Ethnicity, Customized White	517 Participants n=644 Participants	487 Participants n=634 Participants	1004 Participants n=1278 Participants
Race/Ethnicity, Customized Black or African American	90 Participants n=644 Participants	99 Participants n=634 Participants	189 Participants n=1278 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	3 Participants n=644 Participants	2 Participants n=634 Participants	5 Participants n=1278 Participants
Race/Ethnicity, Customized American Indian or Alaska Native, Asian	16 Participants n=644 Participants	27 Participants n=634 Participants	43 Participants n=1278 Participants
Race/Ethnicity, Customized Other	17 Participants n=644 Participants	19 Participants n=634 Participants	36 Participants n=1278 Participants
Race/Ethnicity, Customized Missing	1 Participants n=644 Participants	0 Participants n=634 Participants	1 Participants n=1278 Participants

PRIMARY outcome

Timeframe: At year 1

Outcome measures

Outcome measures
Measure	Semaglutide n=430 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=462 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Number of Participants With Glycosylated Haemoglobin (HbA1c) Less Than 7.0 Percentage (%) (53 Millimoles Per Mole [mmol/Mol]) at Year 1 (Yes/No) Yes	244 Participants	226 Participants
Number of Participants With Glycosylated Haemoglobin (HbA1c) Less Than 7.0 Percentage (%) (53 Millimoles Per Mole [mmol/Mol]) at Year 1 (Yes/No) No	186 Participants	236 Participants

SECONDARY outcome

Timeframe: Baseline (less than or equal to 90 days prior to randomization at week 0), year 1

Change in HbA1c from baseline to year 1 is presented in %-point.

Outcome measures

Outcome measures
Measure	Semaglutide n=430 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=461 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change in HbA1c (Percentage-point [%-Point]) From Baseline to Year 1	-1.46 Percentage-point of HbA1c Standard Deviation 1.669	-1.14 Percentage-point of HbA1c Standard Deviation 1.707

SECONDARY outcome

Timeframe: At year 2

Number of participants who achieved HbA1c less than 7.0 % (53 mmol/mol) at year 2 is presented. Yes: number of participants who achieved HbA1c less than 7.0 % at year 2; No: number of participants who did not achieve HbA1c less than 7.0 % at year 2.

Outcome measures

Outcome measures
Measure	Semaglutide n=374 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=374 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Number of Participants With Glycosylated Haemoglobin (HbA1c) Less Than 7.0% (53 Millimoles Per Mole [mmol/Mol]) at Year 2 (Yes/No) Yes	209 Participants	162 Participants
Number of Participants With Glycosylated Haemoglobin (HbA1c) Less Than 7.0% (53 Millimoles Per Mole [mmol/Mol]) at Year 2 (Yes/No) No	165 Participants	212 Participants

SECONDARY outcome

Timeframe: Baseline (less than or equal to 90 days prior to randomization at week 0), year 2

Change in HbA1c from baseline to year 2 is presented in percentage-point.

Outcome measures

Outcome measures
Measure	Semaglutide n=374 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=373 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change in HbA1c (Percentage-point [%-Point]) From Baseline to Year 2	-1.45 Percentage-point of HbA1c Standard Deviation 1.723	-0.98 Percentage-point of HbA1c Standard Deviation 1.767

SECONDARY outcome

Timeframe: At year 1

Number of participants who attained individualized HbA1c target at year 1 is presented. Study physicians set and documented an individualized HbA1c target for participants prior to randomization based on their clinical judgement and knowledge of the participant. Yes: number of participants who achieved individualized HbA1c target attained at year 1; No: number of participants who did not achieve individualized HbA1c target attained at year 1

Outcome measures

Outcome measures
Measure	Semaglutide n=430 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=462 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Number of Participants Who Attained Individualized HbA1c Target at Year 1 (Yes/No) Yes	216 Participants	170 Participants
Number of Participants Who Attained Individualized HbA1c Target at Year 1 (Yes/No) No	214 Participants	292 Participants

SECONDARY outcome

Timeframe: At year 1

Number of participants who achieved HbA1c less than 7.0% (53 mmol/mol) or at least 1% point improvement in HbA1c compared to baseline at year 1 is presented. Yes: number of participants who achieved HbA1c less than 7.0% or at least 1% point improvement in HbA1c compared to baseline at year 1; No: number of participants who did not achieve HbA1c less than 7.0% or at least 1% point improvement in HbA1c compared to baseline at year 1

Outcome measures

Outcome measures
Measure	Semaglutide n=430 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=462 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Number of Participants With HbA1c Less Than 7.0% (53 mmol/Mol) or At Least 1% Point Improvement in HbA1c Compared to Baseline at Year 1 (Yes/No) Yes	321 Participants	301 Participants
Number of Participants With HbA1c Less Than 7.0% (53 mmol/Mol) or At Least 1% Point Improvement in HbA1c Compared to Baseline at Year 1 (Yes/No) No	109 Participants	160 Participants
Number of Participants With HbA1c Less Than 7.0% (53 mmol/Mol) or At Least 1% Point Improvement in HbA1c Compared to Baseline at Year 1 (Yes/No) Data missing	0 Participants	1 Participants

SECONDARY outcome

Timeframe: At year 1

Number of participants who achieved HbA1c target attainment per HEDIS criteria (less than 8.0% if age ≥ 65 years or with defined comorbidities, otherwise less than 7.0%) at year 1 is presented. Yes: Number of participants who achieved HbA1c target attainment per HEDIS criteria at year 1; No: Number of participants who did not achieve HbA1c target attainment per HEDIS criteria at year 1

Outcome measures

Outcome measures
Measure	Semaglutide n=95 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=98 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Number of Participants With HbA1c Target Attainment Per Healthcare Effectiveness Data and Information Set (HEDIS) Criteria at Year 1 (Yes/No) Yes	64 Participants	53 Participants
Number of Participants With HbA1c Target Attainment Per Healthcare Effectiveness Data and Information Set (HEDIS) Criteria at Year 1 (Yes/No) No	31 Participants	45 Participants

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 1

Change in body weight (in pounds) from baseline to year 1 is presented.

Outcome measures

Outcome measures
Measure	Semaglutide n=458 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=461 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change in Body Weight (in Pounds) From Baseline to Year 1	-9.8 Pounds (lbs) Standard Deviation 21.15	-5.4 Pounds (lbs) Standard Deviation 20.70

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 1

Percentage change in body weight from baseline to year 1 is presented.

Outcome measures

Outcome measures
Measure	Semaglutide n=458 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=461 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Percentage Change in Body Weight From Baseline to Year 1	-3.93 Percentage change in body weight Standard Deviation 11.092	-2.02 Percentage change in body weight Standard Deviation 8.924

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 1

Change in SBP from baseline to year 1 is presented.

Outcome measures

Outcome measures
Measure	Semaglutide n=456 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=457 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change in Systolic Blood Pressure (SBP) From Baseline to Year 1	-2.3 Millimeters of mercury (mmHg) Standard Deviation 16.40	-1.8 Millimeters of mercury (mmHg) Standard Deviation 16.34

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 1

Change in DBP from baseline to year 1 is presented.

Outcome measures

Outcome measures
Measure	Semaglutide n=456 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=457 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change in Diastolic Blood Pressure (DBP) From Baseline to Year 1	-1.6 mmHg Standard Deviation 10.08	-0.9 mmHg Standard Deviation 9.79

SECONDARY outcome

Timeframe: Week 0 to year 2

Time to first study drug discontinuation during 2 years is presented. First study drug discontinuation=date of the first time a patient is not taking study drug as defined.

Outcome measures

Outcome measures
Measure	Semaglutide n=634 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=621 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Time to First Study Drug Discontinuation During 2 Years	1.36 Years Standard Deviation 0.853	1.54 Years Standard Deviation 0.719

SECONDARY outcome

Timeframe: Week 0 to year 2

Time to first treatment intensification (add-on) or change (switch) after randomization during 2 years is presented.

Outcome measures

Outcome measures
Measure	Semaglutide n=575 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=550 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Time to First Treatment Intensification (Add-on) or Change (Switch) After Randomization During 2 Years	1.55 Years Standard Deviation 0.731	1.43 Years Standard Deviation 0.742

SECONDARY outcome

Timeframe: Week 0 to year 1

Percentage of MPR for study drug medication adherence for the first year of the study is presented. Medication adherence referred to a participant's conformance to the provider's recommendation with respect to timing, dosage, and frequency of medication taken during the prescribed length of time. The MPR was used to assess adherence. MPR was calculated as follows: MPR (%) = Sum of days supply for all prescription fills\*100/Total number of days in time period. MPR was capped at 100%. MPR was calculated from pharmacy claims data and irrespective of adherence to randomized treatment or changes to antidiabetic treatment.

Outcome measures

Outcome measures
Measure	Semaglutide n=135 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=134 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Percentage of Medication Possession Ratio (MPR) for Study Drug Medication Adherence for the First Year of the Study	53.1 Percentage of MPR Standard Deviation 40.9	55.8 Percentage of MPR Standard Deviation 41.2

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0) to year 2

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization.

Number of hypoglycemic episodes leading to an inpatient admission or emergency room (ER) encounter from baseline to year 2 is presented.

Outcome measures

Outcome measures
Measure	Semaglutide n=644 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=634 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Number of Hypoglycemic Episodes Leading to an Inpatient Admission or Emergency Room (ER) Encounter From Baseline to Year 2	2 Episodes	1 Episodes

SECONDARY outcome

Timeframe: At year 1

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for DTSQ at the dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

DTSQc total treatment satisfaction score measured at year 1 is presented. The DTSQc provides a measure of how satisfied participants are with their current diabetes treatment compared with previous treatment. It consists of 8 questions, which are to be answered on a Likert scale from -3 to +3 (-3 = much less satisfied now to +3 = much more satisfied now), with 0 (midpoint), representing no change. Six questions are summed to produce a total treatment satisfaction score. The remaining two questions concern perceived frequency of hyperglycemia and perceived frequency of hypoglycemia, respectively. The DTSQc total treatment satisfaction score ranges from -18 to +18, with higher scores associated with greater treatment satisfaction.

Outcome measures

Outcome measures
Measure	Semaglutide n=447 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=460 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc), Total Treatment Satisfaction Score Measured at Year 1	13.5 Scores on a scale Standard Deviation 5.28	12.8 Scores on a scale Standard Deviation 5.82

SECONDARY outcome

Timeframe: At year 2

DTSQc total treatment satisfaction score measured at year 2 is presented. The DTSQc provides a measure of how satisfied participants are with their current diabetes treatment compared with previous treatment. It consists of 8 questions, which are to be answered on a Likert scale from -3 to +3 (-3 = much less satisfied now to +3 = much more satisfied now), with 0 (midpoint), representing no change. Six questions are summed to produce a total treatment satisfaction score. The remaining two questions concern perceived frequency of hyperglycemia and perceived frequency of hypoglycemia, respectively. The DTSQc total treatment satisfaction score ranges from -18 to +18, with higher scores associated with greater treatment satisfaction.

Outcome measures

Outcome measures
Measure	Semaglutide n=388 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=380 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
DTSQc, Total Treatment Satisfaction Score Measured at Year 2	13.2 Scores on a scale Standard Deviation 6.24	12.2 Scores on a scale Standard Deviation 5.87

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 1

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for SF-12 at dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in SF-12 v2, PCS-12 score at year 1 is presented. The SF-12 v2 is a 12-item generic health-related quality of life measure that assesses physical and mental functioning. The items were scored using the scoring software. It contains two summary scores: Physical Component Summary (PCS) Score and Mental Component Summary (MCS) Score. The scores are norm-scored such that the scores range from 0-100 with a mean of 50 and standard deviation of 10. A higher score is associated with better quality of life and a lower score, poorer quality of life.

Outcome measures

Outcome measures
Measure	Semaglutide n=439 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=449 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change From Baseline in Short Form 12-Item Version 2 Survey (SF-12 v2), Physical Component Summary (PCS-12) Score at Year 1	2.8 Scores on a scale Standard Deviation 8.20	2.3 Scores on a scale Standard Deviation 7.60

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 2

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for SF-12 at dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in SF-12 v2, PCS-12 score at year 2 is presented. The SF-12 v2 is a 12-item generic health-related quality of life measure that assesses physical and mental functioning. The items were scored using the scoring software. It contains two summary scores: Physical Component Summary (PCS) Score and Mental Component Summary (MCS) Score. The scores are norm-scored such that the scores range from 0-100 with a mean of 50 and standard deviation of 10. A higher score is associated with better quality of life and a lower score, poorer quality of life.

Outcome measures

Outcome measures
Measure	Semaglutide n=383 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=376 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change From Baseline in SF-12 v2, PCS-12 Score at Year 2	2.6 Scores on a scale Standard Deviation 8.68	2.4 Scores on a scale Standard Deviation 7.99

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 1

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for SF-12 at dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in SF-12 v2, MCS-12 score at year 1 is presented. The SF-12 v2 is a 12-item generic health-related quality of life measure that assesses physical and mental functioning. The items were scored using the scoring software. It contains two summary scores: PCS Score and MCS Score. The scores are norm-scored such that the scores range from 0-100 with a mean of 50 and standard deviation of 10. A higher score is associated with better quality of life and a lower score, poorer quality of life.

Outcome measures

Outcome measures
Measure	Semaglutide n=439 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=449 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change From Baseline in SF-12 v2, Mental Component Summary (MCS-12) Score at Year 1	2.4 Scores on a scale Standard Deviation 8.54	1.1 Scores on a scale Standard Deviation 8.17

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 2

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for SF-12 at dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in SF-12 v2, MCS-12 score at year 2 is presented. The SF-12 v2 is a 12-item generic health-related quality of life measure that assesses physical and mental functioning. The items were scored using the scoring software. It contains two summary scores: PCS Score and MCS Score. The scores are norm-scored such that the scores range from 0-100 with a mean of 50 and standard deviation of 10. A higher score is associated with better quality of life and a lower score, poorer quality of life.

Outcome measures

Outcome measures
Measure	Semaglutide n=383 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=376 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change From Baseline in SF-12 v2, MCS-12 Score at Year 2	2.4 Scores on a scale Standard Deviation 8.43	0.2 Scores on a scale Standard Deviation 9.31

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 1

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for WPAI-GH at the dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in WPAI-GH Absenteeism (work time missed) score at year 1 is presented. The WPAI-GH yields four types of scores: Absenteeism (work time missed), Presenteesism (impairment at work/reduced on-the-job effectiveness), Work productivity loss (overall work impairment/absenteeism plus presenteeism), and Activity Impairment. WPAI outcomes are expressed as impairment percentages (0-100), with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes (percent work time missed due to health, percent impairment while working due to health, percent overall work impairment due to health, percent activity impairment due to health).

Outcome measures

Outcome measures
Measure	Semaglutide n=236 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=241 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change From Baseline in Work Productivity and Activity Impairment, General Health Questionnaire (WPAI-GH) Absenteeism (Work Time Missed) Score at Year 1	-1.5 Scores on a scale Standard Deviation 21.39	0.9 Scores on a scale Standard Deviation 14.39

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 2

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for WPAI-GH at the dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in WPAI-GH Absenteeism (work time missed) score at year 2 is presented. The WPAI-GH yields four types of scores: Absenteeism (work time missed), Presenteesism (impairment at work/reduced on-the-job effectiveness), Work productivity loss (overall work impairment/absenteeism plus presenteeism), and Activity Impairment. WPAI outcomes are expressed as impairment percentages (0-100), with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes (percent work time missed due to health, percent impairment while working due to health, percent overall work impairment due to health, percent activity impairment due to health).

Outcome measures

Outcome measures
Measure	Semaglutide n=204 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=200 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change From Baseline in WPAI-GH Absenteeism (Work Time Missed) Score at Year 2	-2.1 Scores on a scale Standard Deviation 22.86	0.0 Scores on a scale Standard Deviation 14.15

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 1

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for WPAI-GH at the dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in WPAI-GH Presenteeism (Impairment at Work/Reduced On-the-job Effectiveness) score at year 1 is presented. The WPAI-GH yields four types of scores: Absenteeism (work time missed), Presenteesism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment. WPAI outcomes are expressed as impairment percentages (0-100), with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes (percent work time missed due to health, percent impairment while working due to health, percent overall work impairment due to health, percent activity impairment due to health).

Outcome measures

Outcome measures
Measure	Semaglutide n=230 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=238 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change From Baseline in WPAI-GH Presenteeism (Impairment at Work/Reduced On-the-job Effectiveness) Score at Year 1	-5.1 Scores on a scale Standard Deviation 24.31	-4.5 Scores on a scale Standard Deviation 22.25

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 2

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for WPAI-GH at the dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in WPAI-GH Presenteeism (Impairment at Work/Reduced On-the-job Effectiveness) score at year 2 is presented. The WPAI-GH yields four types of scores: Absenteeism (work time missed), Presenteesism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment. WPAI outcomes are expressed as impairment percentages (0-100), with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes (percent work time missed due to health, percent impairment while working due to health, percent overall work impairment due to health, percent activity impairment due to health).

Outcome measures

Outcome measures
Measure	Semaglutide n=196 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=198 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change From Baseline in WPAI-GH Presenteeism (Impairment at Work/Reduced On-the-job Effectiveness) Score at Year 2	-6.0 Scores on a scale Standard Deviation 24.30	-3.8 Scores on a scale Standard Deviation 24.89

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 1

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for WPAI-GH at the dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in WPAI-GH work productivity loss (overall work impairment/absenteeism plus presenteeism) score at year 1 is presented. The WPAI-GH yields four types of scores: Absenteeism (work time missed), Presenteesism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment. WPAI outcomes are expressed as impairment percentages (0-100), with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes (percent work time missed due to health, percent impairment while working due to health, percent overall work impairment due to health, percent activity impairment due to health).

Outcome measures

Outcome measures
Measure	Semaglutide n=229 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=238 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change From Baseline in WPAI-GH Work Productivity Loss (Overall Work Impairment/Absenteeism Plus Presenteeism) Score at Year 1	-4.8 Scores on a scale Standard Deviation 25.64	-4.5 Scores on a scale Standard Deviation 24.79

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 2

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for WPAI-GH at the dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in WPAI-GH work productivity loss (overall work impairment/absenteeism plus presenteeism) score at year 2 is presented. The WPAI-GH yields four types of scores: Absenteeism (work time missed), Presenteesism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment. WPAI outcomes are expressed as impairment percentages (0-100), with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes (percent work time missed due to health, percent impairment while working due to health, percent overall work impairment due to health, percent activity impairment due to health).

Outcome measures

Outcome measures
Measure	Semaglutide n=196 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=198 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change From Baseline in WPAI-GH Work Productivity Loss (Overall Work Impairment/Absenteeism Plus Presenteeism) Score at Year 2	-6.4 Scores on a scale Standard Deviation 25.18	-4.0 Scores on a scale Standard Deviation 25.89

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 1

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for WPAI-GH at the dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in WPAI-GH activity impairment score at year 1 is presented. The WPAI-GH yields four types of scores: Absenteeism (work time missed), Presenteesism (impairment at work/reduced on-the-job effectiveness), Work productivity loss (overall work impairment/absenteeism plus presenteeism), and Activity Impairment. WPAI outcomes are expressed as impairment percentages (0-100), with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes (percent work time missed due to health, percent impairment while working due to health, percent overall work impairment due to health, percent activity impairment due to health).

Outcome measures

Outcome measures
Measure	Semaglutide n=435 Participants Participants received semaglutide subcutaneous (s.c.) injection once weekly in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.	Standard of Care n=445 Participants Participants received standard of care (any commercially available oral or injectable antidiabetic medication, excluding semaglutide) in addition to up to 2 oral antidiabetic medications as treatment intensification for 2 years. Medication dose and dose escalation was at the discretion of the study physician according to routine practice for medications for glycemic control in participants.
Change From Baseline in WPAI-GH Activity Impairment Score at Year 1	-6.7 Scores on a scale Standard Deviation 27.91	-3.7 Scores on a scale Standard Deviation 27.15

SECONDARY outcome

Timeframe: Baseline (less than or equal to 4 weeks prior to the randomization at week 0), year 2

Population: FAS included all randomized participants analyzed according to the treatment group to which they were assigned at randomization. Overall Number of Participants Analyzed = participants with available data for this outcome measure. Analysis is based only on participants with available data for WPAI-GH at the dedicated study visit including measurements irrespective of whether participants discontinued study drug or not.

Change from baseline in WPAI-GH activity impairment score at year 2 is presented. The WPAI-GH yields four types of scores: Absenteeism (work time missed), Presenteesism (impairment at work/reduced on-the-job effectiveness), Work productivity loss (overall work impairment/absenteeism plus presenteeism), and Activity Impairment. WPAI outcomes are expressed as impairment percentages (0-100), with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes (percent work time missed due to health, percent impairment while working due to health, percent overall work impairment due to health, percent activity impairment due to health).