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
Primary result · HbA1c <7.0%Result — go to the resultOdds ratio 1.36 95% CI 1.03–1.79Authors' conclusion
SEPRA demonstrates that semaglutide is an appropriate choice for treatment intensification among individuals with T2D in the USA who are receiving 1-2 antidiabetic medications. Findings support semaglutide as an effective and well-tolerated option in clinical practice.
Study context
- Population
- Adults with T2D and inadequate glycemic control on one or two oral antidiabetic medications, routine clinical practice, USA
- Participants
- 644 vs 634
- Comparison
- Once-weekly subcutaneous semaglutide vs alternative treatment, as add-on therapy
- Semaglutiden = 644
- Alternative treatmentn = 634reference
- Primary endpoint
- Proportion of participants achieving HbA1c <7.0%
- Follow-up
- Year 1
Methodological details2-year, open-label, pragmatic, Missing data were imputed for some analyses
- 2-year
- Open-label
- Pragmatic
- Missing data were imputed for some analyses
Primary result
HbA1c <7.0%
Odds ratio
1.36
95% CI 1.03–1.79
P = 0.033
By group
Semaglutidevs Alternative treatment
OR 1.36 (95% CI 1.03–1.79); P = 0.033
As reported in the abstract
Further findings
| Outcome | Semaglutide | Alternative treatment | OR (95% CI) | P value | |
|---|---|---|---|---|---|
| HbA1c <7.0% · year 2 | 49.9% | 38.9% | 1.56 (1.13–2.16) | P = 0.007 | |
| 0.512Odds ratio (log scale) |
| Outcome | Semaglutide | Alternative treatment | Estimated treatment difference (%) (95% CI) | P value | |
|---|---|---|---|---|---|
| Change in HbA1c · year 1Mean, % | −1.35 | −1.16 | −0.20 (−0.39% to 0.00%) | P = 0.046 | |
| Change in HbA1c · year 2Mean, % | −1.27 | −0.96 | −0.31 (−0.57% to −0.05%) | P = 0.018 | |
| Change in body weight · year 1 | −3.57 % | −1.91 % | −1.65 (−2.92% to −0.39%) | P = 0.010 | |
| −4−202Difference, % (linear scale) |
- Change in body weight · year 2
- P = 0.175
Change in body weight · year 2
- No significantly larger reduction in body weight with semaglutide at year 2
Treatment changes · baseline to year 2
- Treatment changes occurred less frequently with semaglutide than with alternative treatments
Patient-reported outcomes (PROs)
- Some PROs indicated greater improvement with semaglutide vs alternative treatment
Safety
- No new safety concerns were identified
Original publication
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. BMJ Open Diabetes Res Care. Published 15 October 2025. doi:10.
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