A Promising Triple Agonist for Obesity and Diabetes
According to reports by SciTechDaily, an investigational weekly injection known as retatrutide has demonstrated substantial weight loss and improved blood sugar control in adults living with obesity and type 2 diabetes. The findings come from the completed phase 3 trial titled TRIUMPH-2, which involved 1,152 adults across eight countries and was published in The Lancet.
Retatrutide functions as a “triple agonist,” meaning it activates three distinct hormone receptors: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon. Sponsored by manufacturer Eli Lilly, the 80-week trial evaluated the drug alongside dietary counseling and physical activity guidance.
Significant Weight Loss and Blood Sugar Reductions
Participants entered the trial having lived with obesity for a median of 21 years and type 2 diabetes for a median of 5.6 years. By the 80-week mark, individuals assigned to retatrutide experienced dose-dependent weight reductions: an average loss of 11.9% at the 4 mg dose, 16.8% at 9 mg, and 18.8% at the 12 mg dose. By comparison, participants in the placebo group lost an average of 5.1%.
Furthermore, nearly half of the participants receiving the 12 mg dose (47%) achieved a weight loss threshold of at least 20%, while 31% lost at least a quarter of their starting weight. Blood sugar levels also saw marked improvements, with average HbA1c reductions ranging from 1.38 to 1.50 percentage points across the active treatment groups, compared to 0.45 percentage points in the placebo arm.
Safety Profile and Side Effects
While the clinical outcomes are notable, the trial documented higher rates of gastrointestinal side effects among those receiving retatrutide. Diarrhea affected 27% to 34% of participants across the drug groups (compared to 13% for placebo), and nausea affected 14% to 28% (compared to 8% for placebo).
Other reported side effects included low blood pressure events and abnormal skin sensations, such as burning or discomfort (dysesthesia), which affected up to 7% of participants at the highest dose. Permanent treatment discontinuation due to adverse events or death occurred in 12% of the 9 mg group and 8% of the 12 mg group. Seven participants died during the study, though investigators deemed these deaths unrelated to the study intervention.
Researchers are continuing to examine retatrutide’s potential impacts on other obesity-related complications, including cardiovascular disease, metabolic liver disease, knee osteoarthritis, chronic low back pain, and obstructive sleep apnea.