Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial
Authors' conclusion
Retatrutide showed significant improvements in glycaemic control and bodyweight reduction as a monotherapy in adults with type 2 diabetes that is inadequately controlled with diet and exercise alone, with an adverse event profile consistent with molecules with GLP-1 agonist activity, supporting its potential as an effective treatment for type 2 diabetes.
Study context
- Population
- Adults (≥18 years) with T2D inadequately controlled by diet and exercise alone, HbA1c 7.0–9.5% (53–80 mmol/mol), BMI ≥23 kg/m²; mean age 48.8 years, mean HbA1c 7.9%, mean BMI 35.8 kg/m²randomly assigned 1:1:1:1
- Participants
- 537 adults
- Comparison
- Once-weekly SC retatrutide 4 mg, 9 mg or 12 mg vs placebo
- Retatrutide 4 mgn = 134
- Retatrutide 9 mgn = 133
- Retatrutide 12 mgn = 136
- Placebon = 134reference
- Primary endpoint
- Change in HbA1c from baseline
- Follow-up
- Week 40
Methodological detailsphase 3, double-blind, placebo-controlled, multicentre (48 sites, USA, Mexico, India), 490 (91%) completed treatment on study drug; 504 (94%) completed the study
- Phase 3
- Double-blind
- Placebo-controlled
- Multicentre (48 sites, USA, Mexico, India)
- 490 (91%) completed treatment on study drug; 504 (94%) completed the study
Primary result
As reported in the abstract
Mean change in HbA1c from baseline
Retatrutide 4 mg
−1.69
mean · SE 0.11 · %
Retatrutide 9 mg
−1.86
mean · SE 0.10 · %
Retatrutide 12 mg
−1.94
mean · SE 0.08 · %
Placebo
−0.81
mean · SE 0.12 · %
Each group vs placeboEstimated treatment difference, % (95% CI)P value
Retatrutide 4 mg
−0.88(−1.18 to −0.59)
all p<0.0001Retatrutide 9 mg
−1.04(−1.32 to −0.76)
all p<0.0001Retatrutide 12 mg
−1.12(−1.39 to −0.85)
all p<0.0001Secondary outcomes
Mean, %
| Outcome | Retatrutide 4 mg | Retatrutide 9 mg | Retatrutide 12 mg | Placebo |
|---|---|---|---|---|
| Key secondary: mean % change in bodyweight from baseline · week 40 | −11.5 (SE 0.7) | −13.9 (SE 0.8) | −15.3 (SE 0.8) | −2.6 (SE 0.5) |
Safety
Adverse events
- Discontinuations due to AEs, retatrutide
- 2-5%
- Discontinuations due to AEs, placebo
- 0%
- Severe hypoglycaemia
- 0
- Deaths, both retatrutide 4 mg, unrelated to study drug
- 2
- Most frequent AEs with retatrutide: generally mild to moderate gastrointestinal events, subsiding over time
Original publication
Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Lancet. Published 6 June 2026. doi:10.
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