Eli Lilly's retatrutide, a triple GLP-1/GIP/glucagon receptor agonist, has demonstrated promising results in improving lipid and cardiovascular risk profiles in a Phase II clinical trial. The findings, presented at the European Society of Cardiology (ESC) Congress 2024, suggest that retatrutide could become a significant player in the treatment of obesity and related metabolic conditions.
The Phase II trial (NCT04881760) included 338 patients with obesity or overweight, but without diabetes, and analyzed the effects of retatrutide on serum lipid profiles, focusing on changes in apolipoprotein levels and lipoprotein particles. The results indicated a dose-dependent reduction in non-HDL-C, with a decrease of up to 22.2% at 24 weeks and 26.9% at 48 weeks.
Impact on Lipid Profile
In addition to reducing non-HDL-C, retatrutide also significantly lowered apoB levels by up to 19.6% and 24.2% at 24 and 48 weeks, respectively. At 48 weeks, the drug reduced triglycerides and apoC-III levels by up to 40.6% and 38.0%, respectively. Furthermore, retatrutide reduced the total number of triglyceride-rich lipoprotein particles (TRLP), with a greater reduction in large and medium TRLP compared to small TRLP, resulting in a smaller average TRLP size following treatment.
The treatment also led to a reduction in the number of total and highly atherogenic small LDL particles (LDLP), while total and small HDL particles (HDLP) were only slightly reduced. Notably, the average size of HDLP increased after treatment with retatrutide. The NMR-derived lipoprotein insulin resistance score decreased by 27.4%, 31.7%, and 32.5% with the 4mg, 8mg, and 12mg dosages, respectively, at 48 weeks.
Expert Perspectives and Market Potential
Key opinion leaders (KOLs) interviewed, expressed optimism about retatrutide, suggesting it could be the "next step" and a potential replacement for tirzepatide in the long term. GlobalData’s report projects that if retatrutide enters the market in the coming years, it could achieve over $9 billion in sales by 2033 for type 2 diabetes (T2D) and obesity indications.
Clinical Development and Future Directions
Retatrutide is currently in Phase III clinical trials for obesity, T2D, and other conditions. Its mechanism of action, which includes glucagon receptor agonism in addition to GLP-1 and GIP receptor agonism, is expected to target energy consumption. Given the latest results, Eli Lilly may consider seeking approval for cardiovascular risk factors, further expanding the drug's potential applications.
