Lilly has announced promising data from its NCT 04881760 phase 2 study of retatrutide, a potential obesity drug. The drug candidate, a single peptide with agonist activity at the glucose-dependent insulinotropic polypeptide (GIP), GLP-1 and glucagon receptors, was associated with significant weight loss, improved glycemic control and cardiovascular health.
At 24 weeks, retatrutide (1 mg, 4 mg, 8 mg or 12 mg) met the primary endpoint for efficacy in participants with obesity or overweight without diabetes. Participants had a mean weight reduction of up to 17.5% (41.2 lb) at 24 weeks. That figure increased to 24.2% at 48 weeks.
The double-blind, randomized, placebo-controlled study enrolled 338 adults with obesity or overweight and related health conditions to assess the drug’s efficacy, side effects, and safety. Data from that study were published in NEJM.
Lancet recently published data from the separate phase 2 NCT04867785 study on retatrutide, in managing type 2 diabetes and facilitating significant weight loss.
Improved glycemic control and cardiovascular health
Bar graph showing the percentage of weight reduction in patients treated with retatrutide at 24 and 48 weeks.
In addition to weight loss, retatrutide showed promise in improving glycemic control. Prediabetes reverted to normoglycemia in 72% of participants. The drug also showed a positive impact on cardiovascular health markers, including significant reductions in systolic and diastolic blood pressure and an improved lipid profile.
Mild-to-moderate side effects and drug mechanism
The most common adverse events were mild-to-moderate gastrointestinal events, primarily during the dose escalation period. Researchers attribute the drug’s efficacy to its agonistic effects on the glucagon, GIP and GLP-1 receptors, indicating potential roles these receptors play in achieving the therapeutic effects of retatrutide.
Future research: TRIUMPH phase 3 program
Following the positive results from the NCT 04881760 study, Lilly is planning the TRIUMPH Phase 3 program, which will further test retatrutide’s impact on chronic weight management, obstructive sleep apnea, and knee osteoarthritis in people with obesity and overweight. As part of this research, they aim to understand the potential roles these receptors play in achieving the therapeutic effects of retatrutide.
Further context
As the global health community continues to grapple with the obesity epidemic, interest has grown in glucagon-like peptide-1 (GLP-1) receptor agonists. Prominent examples include semaglutide and tirzepatide. While it is difficult to interpret data in separate clinical trials, semaglutide and tirzepatide have also shown promising results in supporting weight loss.
Semaglutide 2.4 mg achieved a mean change in body weight from baseline to week 104 of -15.2% in the phase 3b STEP 5 trial, and 77.1% of participants achieved weight loss ≥5% from baseline at week 104.
Similarly, tirzepatide met primary and key secondary endpoints for efficacy in the phase 3 SURPASS trials, demonstrating consistent safety and efficacy with sustained A1C reduction and progressive weight loss among people with type 2 diabetes.
In related news, Pfizer recently announced that it was dropping development work on a weight loss drug while continuing work on another.
Filed Under: Cardiovascular, Metabolic disease/endicrinology
