Retatrutide is a triple-agonist peptide of the glucagon receptor (GCGR), glucose-dependent insulin-stimulating polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R). Retatrutide has a half-life of about 6 days and is administered once a week.
The effect of Retatrutide on human GCG and GLP-1 receptors was weaker (0.3 and 0.4 times, respectively) and stronger (8.9 times) than on human GIP receptors compared to endogenous receptor ligands.
Subject: 2:1:1:1:1:2: The ratio of 2 is randomly assigned, Receiving Retatrutide 1 mg, 4 mg (initial dose of 2 mg), 4 mg (initial dose of 4 mg), 8 mg (initial dose of 2 mg), 8 mg (initial dose of 4 mg), 12 mg (initial dose of 2 mg) or placebo once a week by subcutaneous injection. Treatment lasted 48 weeks. The primary endpoint was the percentage change in body weight from baseline at week 24; Secondary endpoints included percentage weight change from baseline to 48 weeks (weight loss ≥5%, ≥10%, or ≥15%) and drug safety.
The results showed that:
At 24 weeks, the average weight loss of Retatrutide 12mg group was 18.7 kg (17.5%), the average weight loss of 1 mg group was 7.2%, the average weight loss of 4 mg group was 12.9%, and the average weight loss of 8 mg group was 17.3%. By comparison, the average weight loss in the placebo group was only 1.6 percent.
At 48 weeks, the average weight loss of Retatrutide 12mg group was 26.2 kg (24.2%), the average weight loss of 1 mg group was 8.7%, the average weight loss of 4 mg group was 17.1%, and the average weight loss of 8 mg group was 22.8%. By comparison, the average weight loss in the placebo group was just 2.1 percent.
The results showed that the percentage of weight loss goals (≥5%, ≥10%, and ≥15%) achieved at 48 weeks was 92%, 75%, and 60%, respectively, in the Retatrutide 4 mg group. Retatrutide 8 mg group was 100%, 91% and 75%, respectively. Retatrutide 12 mg group was 100%, 93% and 83%, respectively. That compared with 27 percent, 9 percent and 2 percent in the placebo group.
In terms of drug safety, the most common adverse events in the Retatrutide group were gastrointestinal related events, which were dose-dependent, mostly mild to moderate, and relatively mild in the initial dose (2mg vs. 4mg) group. The “increased heart rate” adverse reaction was also dose-dependent, peaking at 24 weeks and gradually decreasing thereafter.
The findings provide a solid foundation for a Phase 3 trial that will further explore the efficacy and safety of Retatrutide in the treatment of obesity in the future.
Post time: Apr-03-2025