NCT03596450

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

Completed Phase 4 Results posted Last updated 3 July 2024

What this trial tests

Phase 4 trial testing Semaglutide in Diabetes Mellitus, Type 2 in 1,278 participants. Completed in 9 June 2023.

Timeline

13 July 2018

Primary endpoint
9 June 2022

9 June 2023

Quick facts

Lead sponsor	Novo Nordisk A/S
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	1,278
Start date	13 July 2018
Primary completion	9 June 2022
Estimated completion	9 June 2023
Sites	122 locations across Canada, United States

Drugs / interventions tested

• Semaglutide (semaglutide) — full drug profile →
• Standard of care

Conditions studied

• Diabetes Mellitus, Type 2 — all drugs for Diabetes Mellitus, Type 2 →

Sponsor

Novo Nordisk A/S — full company profile →

Who can join

Adults 18 to 65, any sex, with Diabetes Mellitus, Type 2. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Glycosylated Haemoglobin (HbA1c) Less Than 7.0 Percentage (%) (53 Millimoles Per Mole [mmol/Mol]) at Year 1 (Yes/No) Primary · At year 1

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.

Yes

Group	Value	95% CI
Semaglutide	244
Standard of Care	226

No

Group	Value	95% CI
Semaglutide	186
Standard of Care	236

Change in HbA1c (Percentage-point [%-Point]) From Baseline to Year 1 Secondary · 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.

Group	Value	95% CI
Semaglutide	-1.46	± 1.669
Standard of Care	-1.14	± 1.707

Number of Participants With Glycosylated Haemoglobin (HbA1c) Less Than 7.0% (53 Millimoles Per Mole [mmol/Mol]) at Year 2 (Yes/No) Secondary · 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.

Yes

Group	Value	95% CI
Semaglutide	209
Standard of Care	162

No

Group	Value	95% CI
Semaglutide	165
Standard of Care	212

Change in HbA1c (Percentage-point [%-Point]) From Baseline to Year 2 Secondary · 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.

Group	Value	95% CI
Semaglutide	-1.45	± 1.723
Standard of Care	-0.98	± 1.767

Number of Participants Who Attained Individualized HbA1c Target at Year 1 (Yes/No) Secondary · 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

Yes

Group	Value	95% CI
Semaglutide	216
Standard of Care	170

No

Group	Value	95% CI
Semaglutide	214
Standard of Care	292

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) Secondary · 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

Yes

Group	Value	95% CI
Semaglutide	321
Standard of Care	301

No

Group	Value	95% CI
Semaglutide	109
Standard of Care	160

Data missing

Group	Value	95% CI
Semaglutide	0
Standard of Care	1

Number of Participants With HbA1c Target Attainment Per Healthcare Effectiveness Data and Information Set (HEDIS) Criteria at Year 1 (Yes/No) Secondary · 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

Yes

Group	Value	95% CI
Semaglutide	64
Standard of Care	53

No

Group	Value	95% CI
Semaglutide	31
Standard of Care	45

Change in Body Weight (in Pounds) From Baseline to Year 1 Secondary · 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.

Group	Value	95% CI
Semaglutide	-9.8	± 21.15
Standard of Care	-5.4	± 20.70

Percentage Change in Body Weight From Baseline to Year 1 Secondary · 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.

Group	Value	95% CI
Semaglutide	-3.93	± 11.092
Standard of Care	-2.02	± 8.924

Change in Systolic Blood Pressure (SBP) From Baseline to Year 1 Secondary · 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.

Group	Value	95% CI
Semaglutide	-2.3	± 16.40
Standard of Care	-1.8	± 16.34

Change in Diastolic Blood Pressure (DBP) From Baseline to Year 1 Secondary · 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.

Group	Value	95% CI
Semaglutide	-1.6	± 10.08
Standard of Care	-0.9	± 9.79

Time to First Study Drug Discontinuation During 2 Years Secondary · 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.

Group	Value	95% CI
Semaglutide	1.36	± 0.853
Standard of Care	1.54	± 0.719

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to year 2 (week 104). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Semaglutide

Serious: 38/634 (6%)

Deaths: 9/634

Standard of Care

Serious: 39/621 (6%)

Deaths: 9/621

Serious adverse events (83 terms)

Reaction	System	Semaglutide	Standard of Care
Coronavirus infection	Infections and infestations	—	—
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Death	General disorders	—	—
Pneumonia	Infections and infestations	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Coronary artery disease	Cardiac disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Cellulitis	Infections and infestations	—	—
Gastroenteritis	Infections and infestations	—	—
Abdominal sepsis	Infections and infestations	—	—
Cystitis	Infections and infestations	—	—
Disseminated varicella zoster vaccine virus infection	Infections and infestations	—	—
Meningitis	Infections and infestations	—	—
Osteomyelitis	Infections and infestations	—	—
Osteomyelitis acute	Infections and infestations	—	—
Peritonitis	Infections and infestations	—	—
Pyelonephritis acute	Infections and infestations	—	—
Septic shock	Infections and infestations	—	—
Cardiac failure acute	Cardiac disorders	—	—
Arteriosclerosis coronary artery	Cardiac disorders	—	—
Cardiac failure	Cardiac disorders	—	—
Cardiac failure congestive	Cardiac disorders	—	—
Cardio-respiratory arrest	Cardiac disorders	—	—
Coronary artery dissection	Cardiac disorders	—	—

Most-reported serious reactions: Coronavirus infection, Acute respiratory failure, Death, Pneumonia, Acute myocardial infarction, Coronary artery disease, Atrial fibrillation, Respiratory failure.

Data from ClinicalTrials.gov NCT03596450 adverse events section.

Sponsor's own description

The main purpose of this study is to compare the effects of semaglutide (Ozempic®) with the effects of other treatments for type 2 diabetes in a normal practice setting. The participant will be assigned by chance (like flipping a coin) to one of the following treatment groups: Group 1: semaglutide (Ozempic®) (by injection into skin) Group 2: standard of care antidiabetic medication (oral or injectable). The participant has an equal chance of being in either of the treatment groups. Neither the participant nor the study doctor or study staff will be able to pick which group the participant is in, but the participant will know which study drug the participant has been assigned to. The study doctor will provide the participant with a prescription for the study diabetes medication based on the treatment group the participant is assigned. The participation will last about 2 years.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Study design and baseline profile for adults with type 2 diabetes in the once-weekly subcutaneous SEmaglutide randomized PRAgmatic (SEPRA) trial.
   Buse JB, Nordahl Christensen H, Harty BJ, Mitchell J, et al · · 2023 · cited 14× · PMID 37137527 · DOI 10.1136/bmjdrc-2022-003206
2. Clinical Trials With Pragmatic Elements: A Review of Use Cases and Real-World Data Utilization.
   Su L, Chen L, Betigeri S, Dreyer N, et al · · 2025 · cited 3× · PMID 40827586 · DOI 10.1002/cpt.70033
3. Long-term comparative effectiveness of once-weekly semaglutide versus alternative treatments in a real-world US adult population with type 2 diabetes: a randomized pragmatic clinical trial.
   Buse JB, Nordahl Christensen H, Harty BJ, Cziraky MJ, et al · · 2025 · cited 1× · PMID 41093600 · DOI 10.1136/bmjdrc-2025-005161
4. Effect of semaglutide on arrhythmic, major cardiovascular, and microvascular outcomes in patients with type 2 diabetes: a systematic review and meta-analysis.
   Wu R, Xing B, Huang Y, Zhou Z, et al · · 2025 · cited 1× · PMID 40933383 · DOI 10.3389/fendo.2025.1554795