Eli Lilly’s GLP-1R/GIPR/GCGR agonist achieves success in Phase III weight loss study
On May 21, Eli Lilly announced positive results from the Phase III TRIUMPH-1 trial of Retatrutide, a GLP-1R/GIPR/GCGR agonist, for weight reduction.
TRIUMPH-1 is an 80-week, randomized, double-blind, placebo-controlled Phase III trial (n=2339) evaluating the efficacy and safety of Retatrutide (4/9/12 mg once weekly) in adults with obesity or overweight who have at least one weight-related comorbidity but do not have diabetes.
From the treatment‑effect estimand:
At 80 weeks, participants in the 4 mg, 9 mg, and 12 mg groups achieve mean weight reductions of -19.0% (-47.2 lb), -25.9% (-64.4 lb), and -28.3% (-70.3 lb), respectively, compared with -2.2% (-5.5 lb) in the placebo group. Notably, 65.3% of participants receiving the 12 mg dose achieve a BMI below 30, of whom 37.5% have a baseline BMI ≥40.
At 104 weeks, the 4 mg, 9 mg, and 12 mg groups show mean weight reductions of -27.9% (-73.3 lb), -29.5% (-80.7 lb), and -30.3% (-85.0 lb), respectively, compared with -19.2% (-49.9 lb) in the placebo group.
In addition, Retatrutide demonstrates significant improvements in certain cardiovascular risk factors, including waist circumference, non‑HDL cholesterol, triglycerides, systolic blood pressure, and high‑sensitivity C‑reactive protein (hsCRP).
From the treatment‑regimen estimand:
At 80 weeks, participants in the 4 mg, 9 mg, and 12 mg groups achieve mean weight reductions of -17.6% (-19.8 kg, -43.7 lb), -23.7% (-26.7 kg, -58.9 lb), and -25.0% (-28.2 kg, -62.1 lb), respectively, compared with -3.9% (-4.4 kg, -9.7 lb) in the placebo group.
At 104 weeks, the 4 mg, 9 mg, and 12 mg groups show mean weight reductions of -25.7% (-30.6 kg, -67.5 lb), -28.7% (-35.6 kg, -78.4 lb), and -29.9% (-38.1 kg, -83.9 lb), respectively, compared with -18.9% (-22.3 kg, -49.1 lb) in the placebo group.
Regarding safety, the most common adverse events in the Retatrutide groups (4 mg, 9 mg, 12 mg vs placebo) include nausea (28.6%, 38.4%, 42.4% vs 14.8%), diarrhea (25.2%, 34.1%, 32.0% vs 13.5%), constipation (23.8%, 25.9%, 26.1% vs 10.9%), vomiting (10.6%, 22.8%, 25.3% vs 4.8%), and upper respiratory tract infection (14.2%, 12.2%, 13.1% vs 11.6%).
The incidence of paresthesia in the Retatrutide (4 mg, 9 mg, 12 mg) groups is 5.1%, 12.3%, and 12.5%, respectively, compared with 0.9% in the placebo group; the incidence of urinary tract infection is 7.5%, 8.8%, and 8.4%, respectively, compared with 5.3% in the placebo group. Paresthesia and urinary tract infection events are generally mild to moderate, most resolve during the treatment course, and the majority of participants continue Retatrutide. Discontinuation rates due to adverse events are 4.1%, 6.9%, and 11.3% in the Retatrutide (4 mg, 9 mg, 12 mg) groups, respectively, compared with 4.9% in the placebo group.
