Plate Nº 52 · recorded October 1, 2026
Health & Medicine ResearchReported finding
Triple-Action Drug Retatrutide Delivers Major Weight Loss in Type 2 Diabetes
In an 80-week phase 3 trial, the triple hormone agonist retatrutide cut body weight by up to 18.8% and lowered HbA1c in people with obesity and type 2 diabetes.
By Marcus Bennett4 min read900 words
In brief
- Retatrutide (12 mg) produced a mean 18.8% body weight reduction at 80 weeks versus 5.1% with placebo in people with obesity or overweight and type 2 diabetes.
- At the highest dose, 47% of participants lost at least 20% of their body weight, and 72% reached an HbA1c of 6.5% or lower.
- The most common side effects were gastrointestinal (nausea and diarrhoea); the drug is investigational and not yet approved.
An investigational drug called retatrutide produced substantial weight loss and improved blood sugar control in people living with obesity or overweight and type 2 diabetes, according to results from a completed phase 3 trial published in The Lancet and presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy (September 28 – October 2).
The findings matter because this population has historically responded less well to obesity medications than people without diabetes.
Study co-author Dr. Juan Pablo Frías, Medical Director and Principal Investigator at the Los Angeles Institute for Metabolic Research, presented the study design and efficacy results. Eli Lilly, the drug's manufacturer, sponsored the trial.
How the drug works
Retatrutide is a "triple agonist." In plain terms, it mimics three natural gut hormones at once — glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon — by binding to their receptors. Researchers are studying it for obesity, type 2 diabetes, and other obesity-related conditions including cardiovascular disease, metabolic liver disease, knee osteoarthritis, chronic low back pain, and obstructive sleep apnea.
The trial design
The 80-week TRIUMPH-2 trial was randomized, double-blind, and placebo-controlled — meaning neither participants nor researchers knew who received the active drug. It ran at 92 sites across 8 countries: Argentina, Australia, Brazil, India, Mexico, Romania, Spain, and the United States.
Eligible adults were 18 or older, had a body mass index (BMI) of at least 27 kg/m², and type 2 diabetes with glycated hemoglobin (HbA1c, a measure of average blood sugar over roughly three months) between 6.5% and 10.5%.
Researchers randomly assigned 1,152 of the 2,047 screened participants in equal proportions to once-weekly injections of placebo, retatrutide 4 mg, 9 mg, or 12 mg, alongside dietary counseling and physical activity guidance. The primary endpoint was percent change in body weight at week 80; HbA1c change was a key secondary endpoint.
At the start, participants had a mean age of 55.1 years, mean BMI of 38.2 kg/m², and mean HbA1c of 7.71%. Median duration of obesity was 21 years; median duration of diabetes was 5.6 years. Some 92% were already taking oral glucose-lowering medication. Of those enrolled, 1,046 (91%) completed the study, including 965 (84%) who stayed on their assigned treatment.
What the study found
The weight-loss results were dose-dependent. At week 80, mean body weight fell 11.9% with the 4 mg dose, 16.8% with 9 mg, and 18.8% with 12 mg, compared with 5.1% with placebo. The estimated treatment differences versus placebo were −6.9%, −11.8%, and −13.8%, respectively.
Blood sugar also improved. HbA1c dropped by 1.38%, 1.50%, and 1.45% in the 4 mg, 9 mg, and 12 mg groups, versus 0.45% with placebo.
At the highest dose, 47% of participants lost at least 20% of their starting weight, and 31% lost at least 25% — compared with just 6% and 3%, respectively, in the placebo group. In addition, 72% of those on 12 mg achieved an HbA1c of 6.5% or lower, versus 29% on placebo.
Retatrutide also improved cardiometabolic risk factors, including blood pressure and lipid profiles, and reduced high-sensitivity C-reactive protein (hsCRP), a blood marker of inflammation.
Side effects and safety
The most common adverse events were gastrointestinal, and they occurred more often in the retatrutide groups. Diarrhoea affected 27–34% of retatrutide recipients (80–96 participants depending on dose) versus 13% (38 participants) on placebo. Nausea affected 14–28% versus 8% (23 participants) with placebo.
Low blood pressure events — hypotension, orthostatic hypotension, or decreased blood pressure — occurred in 1%, 5%, and 6% of the 4 mg, 9 mg, and 12 mg groups, respectively, versus less than 1% on placebo. Dysesthesia, abnormal skin sensations such as burning or discomfort, occurred in 4%, 6%, and 7% of the dose groups versus 1% on placebo; none of these events were severe or serious.
Permanent discontinuation due to adverse events or death was more common at higher doses: 12% (33 participants) with 9 mg and 8% (22 participants) with 12 mg, versus 4% (11 participants) with 4 mg and 5% (14 participants) with placebo. Seven deaths occurred during the study — 2 in the 4 mg group, 3 in the 9 mg group, 1 in the 12 mg group, and 1 in the placebo group. Investigators deemed all of them unrelated to the study intervention.
What comes next
"There is an unmet need for more efficacious weight reduction in individuals with obesity and type 2 diabetes," the authors write. "Findings from TRIUMPH-2 suggest that retatrutide may advance the treatment of obesity and type 2 diabetes, a population where weight reduction has been challenging to achieve."
They add: "Retatrutide demonstrated substantial reduction in body weight alongside improvements in blood sugar control and cardiometabolic risk factors, with a safety profile generally similar to other molecules with GLP-1 receptor agonist activity. These findings support obesity treatment as a strategy for people with obesity and type 2 diabetes. Further studies are required to determine whether these benefits translate to improvements in other obesity-related complications."
Retatrutide remains investigational. It has not yet received regulatory approval, and longer-term data will be needed to confirm whether these benefits extend to the many obesity-related conditions researchers hope to address.
via Medical Xpress (Source)