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Clinical trial participants with obesity and type 2 diabetes mellitus (T2DM), who took retatrutide at a dose of 12 mg, experienced an average of 20.8% weight loss over 80 weeks, with more than half no longer meeting the BMI criteria for obesity by the end of the trial, study results show.
The investigational triple agonist drug targets GIP, GLP-1 and glucagon receptors, which has previously shown promise in people without diabetes, who lost an average of 28.3% of their body weight in 80 weeks on 12 mg retatrutide.
The results of the TRIUMPH-2 study were presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes and simultaneously published in The Lancet on 29 September 2026.
Researchers analysed data from 2,047 participants, with a BMI of 27 or higher and T2DM who were randomly assigned retatrutide 4 mg, 9 mg or 12 mg, or placebo.
Participants with T2DM who took retatrutide 4 mg, 9 mg and 12 mg, lost an average of 29.8 lbs (12.7%), 45.4 lbs (19.1%) and 49.6 lbs (20.8%), respectively, the study results showed.
Researchers also observed that nearly one-quarter (23.4%) of participants with a baseline BMI of 35 or higher, who took retatrutide 12 mg, lost an average of 60.8 lbs.
In a press release published alongside the findings, manufactuerer Lilly said that by the end of the study, more than half (59.5%) of participants who took retatrutide 12 mg no longer met the BMI criteria for obesity.
Commenting on the study, Philip Newland-Jones, consultant pharmacist and honorary associate professor in diabetes and endocrinology at the University of Southampton, said the results of the TRIUMPH-2 study were “particularly striking” in the level of weight loss achieved in people with T2DM.
“Historically, weight-loss medicines have tended to produce less weight reduction in people with diabetes than in those without diabetes, making the average of almost 21% weight loss with retatrutide especially impressive,” he added.
Newland-Jones also noted the impact of retatrutide on blood sugar levels, adding that “the results are promising in keeping with existing data that targeting multiple nutrient-stimulating hormone pathways concurrently leads to greater effects on HbA1c and weight loss than GLP-1 alone”.
In the TRIUMPH-2 study, researchers observed that retatrutide reduced blood sugar level A1C by an average of 1.6%, with up to 40.0% of participants lowering their A1C measure by more than 5.7%.
“As with other incretin-based therapies recently entering the market for a range of indications, such as tirzepatide, Wegovy [semaglutide; Novo Nordisk] and orforglipron, retatrutide will raise further questions about affordability and equitable access across the NHS,” Newland-Jones said.
“Ensuring patients can benefit from effective and innovative medicines will require funding to manage the initial local cost pressures if we are to realise the longer-term reductions in complications and associated healthcare costs.”
Helen O’Neil, senior medicines optimisation pharmacist at North East and North Cumbria Integrated Care Board, commented: “Phase III data show retatrutide delivers significant weight loss in people with T2DM and obesity, offering a potential alternative where other GLP-1 therapies have been ineffective or poorly tolerated.
“Side effects appear similar to other incretin-based therapies, but head-to-head studies are needed to determine its place in treatment pathways.”
In February 2026, the National Institute for Health and Care Excellence expanded NHS access to GLP-1 receptor agonists, such as semaglutide, dulaglutide and liraglutide, and the related medicine tirzepatide.
