Revolutionizing Weight Loss: The Rise of GLP-1 and Incretin-Based Drugs

Researchers have developed a new generation of weight-loss drugs that mimic the effects of glucagon-like peptide-1 (GLP-1), a hormone that regulates appetite and metabolism. The new drugs, such as a small molecule developed by Japan's Chugai Pharmaceutical Co, can be taken orally and are as effective as injectable GLP-1 drugs like semaglutide. However, they have also been associated with gastrointestinal side effects. The development of these drugs is seen as a major breakthrough in the treatment of obesity and potentially has the power to revolutionise health-span.

Researchers have developed a new generation of weight-loss drugs that mimic the effects of glucagon-like peptide-1 (GLP-1), a hormone that regulates appetite and metabolism. These drugs, such as a small molecule developed by Japan's Chugai Pharmaceutical Co., can be taken orally and are as effective as injectable GLP-1 drugs like semaglutide. However, they have also been associated with gastrointestinal side effects. The development of these drugs is seen as a major breakthrough in the treatment of obesity and potentially has the power to revolutionize healthspan.

Terns Pharmaceuticals (TERN) recently reported positive phase 1 results for its experimental weight loss treatment TERN-601. TERN-601, a once-daily oral GLP-1 receptor agonist, helped patients lose up to 5.5% of body weight over 28 days, with 67% of participants on the highest dose losing at least 5%, meeting the trial's primary endpoint [1]. The drug was well tolerated with no treatment-related interruptions or dropouts, and most side effects were mild, even with rapid dose increases every three days. Terns has completed enrollment for its phase 2 trial, which will test weight loss results over 12 weeks and compare them with a placebo, expecting topline results by the end of 2025.

Eli Lilly and Company (NYSE: LLY) also announced detailed results from ACHIEVE-1, a Phase 3 trial evaluating the safety and efficacy of orforglipron, a novel oral small-molecule GLP-1 receptor agonist. The investigational once-daily pill lowered A1C by an average of 1.3% to 1.6% across doses, with improvements seen as early as four weeks, in adults with type 2 diabetes. Orforglipron also led to an average weight loss of 16.0 lbs (7.9%) at the highest dose by week 40 in a key secondary endpoint. The safety profile of orforglipron was consistent with the established GLP-1 class, and the most frequently reported adverse events were gastrointestinal-related [2].

The development of these oral GLP-1 receptor agonists represents a significant advancement in the treatment of obesity and type 2 diabetes. They offer a more convenient option for patients who prefer oral medications over injectables. However, the potential for gastrointestinal side effects remains a consideration. Further clinical trials are needed to fully understand the long-term effects and safety profiles of these drugs.

References:
[1] https://finance.yahoo.com/news/terns-pharmaceuticals-reports-positive-phase-211219068.html
[2] https://www.biospace.com/press-releases/lillys-oral-glp-1-orforglipron-showed-compelling-efficacy-and-a-safety-profile-consistent-with-injectable-glp-1-medicines-in-complete-phase-3-results-published-in-the-new-england-journal-of-medicine