Retatrutide Phase 3 Data Show Up to 28.3% Weight Loss, First Triple Hormone Agonist Results in Obesity and Type 2 Diabetes
核心洞察
Eli Lilly's retatrutide, a GIP/GLP-1/glucagon triple hormone receptor agonist, met primary endpoints in two phase 3 trials presented at the ADA 2026 Scientific Sessions.
In TRIUMPH-1, adults with obesity (搜索) taking retatrutide 12 mg weekly lost an average 28.3% of body weight over 80 weeks, with 65.3% falling below the BMI 30 obesity threshold.
In TRANSCEND-T2D-1, adults with recent-onset type 2 diabetes (搜索) lost up to 16.8% of body weight and achieved A1C reductions of up to 2% over 40 weeks.
Retatrutide, an investigational once-weekly triple hormone receptor agonist, produced substantial weight loss and glycemic improvements in two phase 3 trials in people with obesity (搜索) and in people with recent-onset type 2 diabetes (搜索), according to results presented at the 2026 Scientific Sessions of the American Diabetes Association in New Orleans and published simultaneously in The Lancet and the New England Journal of Medicine.
The drug, developed by Eli Lilly, targets three naturally occurring hormones, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and glucagon. According to the American Diabetes Association, the mechanism is designed to reduce appetite, improve insulin response, increase energy use and promote fat metabolism.
TRIUMPH-1: 28.3% Weight Loss at 80 Weeks
The phase 3 TRIUMPH-1 trial evaluated retatrutide for weight reduction in 2,339 adults with obesity (搜索) or overweight, including a subset with knee osteoarthritis (搜索) and/or obstructive sleep apnea (搜索). Participants were randomly assigned to once-weekly injections of 4 mg, 9 mg or 12 mg retatrutide, or placebo, for 80 weeks.
For the primary endpoint, participants taking 9 mg and 12 mg lost an average of 64.4 lbs (25.9%) and 70.3 lbs (28.3%) respectively. Those taking the 4 mg dose, administered with a single dose escalation step, lost an average of 47.2 lbs (19.0%). At 80 weeks, 65.3% of participants on the 12 mg dose achieved a BMI below 30, falling under the threshold for obesity (搜索).
Retatrutide also produced significant improvements from baseline across certain cardiovascular risk factors, including triglycerides, systolic blood pressure and high-sensitivity C-reactive protein (hsCRP).
"Affecting nearly half of Americans, obesity (搜索) is a chronic neurometabolic disease which is associated with over two hundred obesity-related conditions," said Ania M. Jastreboff, MD, PhD, professor at Yale and lead author of the study. "Treatment with retatrutide, the first triple hormone receptor agonist in phase 3 of development for obesity, resulted in substantial weight reduction with nearly two thirds of participants reaching targets below the obesity threshold."
Jastreboff added that treatment also resulted in improvements in health outcomes, "from decreased knee pain to fewer sleep disturbances, to clear improvements in cardiometabolic measures."
TRANSCEND-T2D-1: Weight Loss in a Historically Harder-to-Treat Population
The phase 3 TRANSCEND-T2D-1 trial evaluated retatrutide monotherapy in 537 adults with recent-onset type 2 diabetes (搜索) (mean duration 2.5 years) and a BMI of at least 23 kg/m² whose glycemic control was inadequate (A1C between 7.0% and 9.5%) despite diet and exercise alone and without other diabetes medications. The randomized, double-blind, placebo-controlled trial assigned participants to once-weekly injections of 4 mg, 9 mg or 12 mg retatrutide, or placebo, over 40 weeks.
Participants experienced up to a 2% reduction in A1C and a 16.8% reduction in body weight, an average loss of 36.6 lbs. Retatrutide also improved LDL cholesterol, triglycerides and blood pressure. Adverse events were low and similar to those of GLP-1 receptor (搜索) agonists already in use, with no new safety concerns reported. The weight loss observed did not reach its maximum magnitude by the end of 40 weeks.
"It is well established that weight reduction with currently available medications is often less for people living with type 2 diabetes (搜索) compared to those without diabetes," said Harpreet Singh Bajaj, MD, MPH, lead author of the study. "As no other trial has reported this magnitude of weight loss, this novel treatment retatrutide has the potential to meaningfully improve the lives of newly diagnosed individuals with type 2 diabetes through life-changing weight and blood glucose management."
Bajaj added that the magnitude of weight loss observed "has the potential to slow disease progression and reshape how we treat and manage type 2 diabetes (搜索)."
The American Diabetes Association notes that approximately 90% of people with type 2 diabetes (搜索) also live with overweight or obesity (搜索), and that achieving both A1C control and meaningful weight loss remains a significant gap for many patients.
Additional Data in Diabetes and Non-Diabetes Populations
A separate study published in the New England Journal of Medicine reported similar weight-loss benefits in people who were overweight or obese but did not have diabetes. In that study, people taking the highest dose of retatrutide lost about 25% of their starting body weight, compared with 3.9% of those taking placebo. Participants with knee osteoarthritis (搜索) reported lower pain scores than those on placebo, and people with obstructive sleep apnea (搜索) reported fewer apnea episodes.
In the Lancet-published diabetes study, people taking the highest dose lost about 18.8% of their starting body weight versus 5.1% for placebo over 1.5 years. About a third of participants on the highest dose lost at least 25% of their body weight, compared with 3% of those on placebo. Among those taking the highest dose, 63% lowered their A1C to less than 6.5%, the threshold for diabetes, and lost at least 10% of their body weight.
"This is the most potent drug, showing the greatest percent weight loss in people with Type 2 diabetes (搜索) with a pharmacological agent, shown to date," said Dr. Juan Pablo Frias, medical director at the Los Angeles Institute for Metabolic Research and one of the Lancet study authors.
Ongoing Phase 3 Program
Study authors noted that additional phase 3 trials are underway. TRANSCEND-T2D-2 is investigating retatrutide versus semaglutide, a GLP-1 receptor (搜索) agonist, over 80 weeks. TRANSCEND-T2D-3 is evaluating retatrutide versus placebo in combination with insulin in individuals with chronic kidney disease (搜索) over one year. TRIUMPH-2 is assessing retatrutide in people with obesity (搜索) and type 2 diabetes (搜索), and TRIUMPH-3 in people with obesity and cardiovascular disease (搜索).
The phase 3 results follow positive phase 2 data for retatrutide.