A Phase III randomised controlled trial published in The Lancet has found that retatrutide, a triple receptor agonist targeting GIP, GLP-1, and glucagon pathways simultaneously, produced substantial improvements in glycaemic control and body weight in adults with type 2 diabetes inadequately managed through diet and exercise alone.
The TRANSCEND-T2D-1 trial enrolled 537 adults across 48 sites in the United States, Mexico, and India. Participants received once-weekly subcutaneous injections of retatrutide at doses of 4 mg, 9 mg, or 12 mg, or placebo, over 40 weeks. The trial was designed to assess both glycaemic outcomes and weight reduction across dose levels.
Nearly 90% of participants receiving retatrutide achieved an HbA1c below 7.0%, with up to 40% reaching levels below 5.7%, within the normoglycaemic range. Fasting serum glucose levels also fell significantly across all active treatment groups. Participants lost an average of 11.5% to 15.3% of body weight depending on dose, compared with 2.6% in the placebo group. Those receiving the highest dose lost 15.3% on average, with weight loss still ongoing at the end of the 40-week period. Additional benefits included reductions in waist circumference, cholesterol levels, and blood pressure. Sixty-four per cent of participants in the highest dose group achieved the composite target of HbA1c below 6.5% and weight loss of at least 10%.
No cases of severe hypoglycaemia were reported. The most common adverse effects were gastrointestinal, including nausea, diarrhoea, and vomiting, and were generally mild to moderate in severity.
The authors note that longer-term studies across broader patient populations are needed to evaluate the drug’s safety profile and suitability as a first-line therapy for early type 2 diabetes.
Source: Bajaj HS et al. Efficacy and safety of retatrutide in people with type 2 diabetes (TRANSCEND-T2D-1). The Lancet (2026). DOI: 10.1016/s0140-6736(26)00967-0.
