High-Dose Semaglutide (Up to 16 mg) in People With Type 2 Diabetes and Overweight or Obesity: A Randomized, Placebo-Controlled, Phase 2 Trial
Authors' conclusion
Higher semaglutide doses for type 2 diabetes and overweight or obesity provide modest additional glucose-lowering effect, with additional weight loss, at the expense of more AEs and treatment discontinuations. A study for evaluating high-dose semaglutide in obesity is currently underway.
Study context
- Population
- Individuals with T2D and BMI ≥27 kg/m² on metformin
- Participants
- 245 individuals
- Comparison
- Weekly semaglutide 2, 8 or 16 mg s.c. vs placebo
- Primary endpoint
- Change from baseline in HbA1c
- Follow-up
- Week 40
Methodological detailsparallel-group, participant- and investigator-blinded, placebo-controlled, phase 2, Doses escalated every 4 weeks, followed by a maintenance period; dose modifications not allowed
- Parallel-group
- Participant- and investigator-blinded
- Placebo-controlled
- Phase 2
- Doses escalated every 4 weeks, followed by a maintenance period; dose modifications not allowed
Primary result
As reported in the abstract
Change in HbA1c from baseline
16 mg vs 2 mgEstimated treatment difference, %-points (95% CI)P value
Treatment policy estimand
−0.3(−0.7 to 0.2)
P = 0.245Hypothetical estimand
−0.5(−1.0 to −0.1)
P = 0.015Secondary outcomes
| Outcome | Estimated treatment difference (kg) (CI) | P value | |
|---|---|---|---|
| Change in body weight from baseline · week 4016 mgvs 2 mgTreatment policy estimand | −3.4 (−6.0 to −0.8) | P = 0.011 | |
| Change in body weight from baseline · week 4016 mgvs 2 mgHypothetical estimand | −4.5 (−7.6 to −1.4) | P = 0.004 | |
| −10−505Difference, kg (linear scale) |
Safety
- Severe hypoglycemic episodes
- 0
- Treatment-emergent adverse events (AEs) and discontinuations due to AEs, primarily gastrointestinal, more frequent with semaglutide 8 and 16 mg than 2 mg
Original publication
High-Dose Semaglutide (Up to 16 mg) in People With Type 2 Diabetes and Overweight or Obesity: A Randomized, Placebo-Controlled, Phase 2 Trial. Diabetes Care. Published 25 April 2025. doi:10.
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