An experimental drug that targets three metabolic pathways has shown promising results in people with type 2 diabetes.
An experimental drug that targets three metabolic pathways has produced substantial improvements in blood sugar control and weight loss in people with type 2 diabetes. In a phase 3 clinical trial published in The Lancet, participants receiving the once-weekly injection lost an average of up to 15.3% of their body weight over 40 weeks, alongside significant reductions in long-term blood sugar levels.
The drug, called retatrutide, belongs to an emerging generation of treatments designed to influence several hormones involved in metabolism. Unlike existing medications that activate one or two hormone receptors, retatrutide acts on three, potentially offering a different approach to treating diabetes and obesity.
Significant Improvements in Blood Sugar and Weight
The trial found that retatrutide reduced HbA1c, a measure of average blood sugar over approximately three months, by 1.69 to 1.94 percentage points, depending on the dose. Participants receiving a placebo experienced a smaller reduction of 0.81 percentage points.
Weight loss also increased with the dose. Participants receiving 4 mg, 9 mg, or 12 mg of retatrutide lost an average of 11.5%, 13.9%, and 15.3% of their body weight, respectively. Those given a placebo lost an average of 2.6%.
How Retatrutide Differs From Ozempic and Mounjaro
Retatrutide activates three hormone receptors involved in regulating blood sugar, appetite, and energy metabolism: GIP, GLP-1, and glucagon. By comparison, Ozempic targets GLP-1, while Mounjaro activates both GLP-1 and GIP.
The addition of glucagon receptor activity could help explain retatrutide’s effects on body weight. Although glucagon normally helps raise blood sugar, it also influences how the body uses and expends energy. Combining its activity with GLP-1 and GIP signaling may support weight loss while maintaining improved glucose control. However, the trial did not directly establish how much each pathway contributed to the observed benefits.
Promising Results, but Longer-Term Safety Remains Under Study
Researchers conducted the 40-week trial at 48 sites across the United States, Mexico, and India. Of 930 adults screened, 537 were randomly assigned to receive one of three retatrutide doses or a placebo. All participants had type 2 diabetes that was inadequately controlled through diet and exercise alone and were not taking diabetes medications.
The most common side effects were gastrointestinal problems, generally mild to moderate, that tended to improve over time. Between 2% and 5% of participants receiving retatrutide discontinued treatment because of adverse events. No severe hypoglycemia was reported. Two participants died during the study, but both deaths were assessed as unrelated to the treatment.
Although the results support retatrutide’s potential as a diabetes treatment, the study did not compare it directly with currently available drugs such as Ozempic or Mounjaro. Additional clinical trials and longer-term follow-up are needed to determine whether its benefits persist and to better establish its safety profile.
Reference: “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” by Harpreet S Bajaj, Michelle Welch, Parag Shah, Eduardo Luna, Fatima-Zahra Jaouimaa, Bing Liu, Rong Liu, Yanyun Chen, Hiren Patel and Amy Bartee, 6 June 2026, The Lancet.
DOI: 10.1016/S0140-6736(26)00967-0
Funding: Eli Lilly and Company
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