Drug company Eli Lilly is testing a next-generation weight-loss medicine that has produced the largest results ever recorded for this class of drugs, and a striking side benefit that surprised even researchers.
The drug is called retatrutide, and according to results announced in December 2025, participants in a 68-week clinical trial lost an average of 28.7 percent of their body weight at the highest dose. According to Eli Lilly, that is roughly 71 pounds for the average participant. By comparison, the popular weight-loss drug Wegovy produces about 15 percent loss, and Zepbound about 22.5 percent.
Retatrutide works by activating three of the body's natural hormones at once, GLP-1, GIP, and glucagon, which is why scientists call it a "triple agonist." The third hormone, glucagon, helps the body burn more energy, in addition to the appetite-suppressing effects of the other two. Existing drugs like Wegovy work on only one or two of these pathways.
The unexpected finding came from a trial focused on adults with both obesity and knee osteoarthritis. According to Rheumatology Advisor, retatrutide reduced knee pain by up to 75.8 percent, a larger drop than weight loss alone would predict. Researchers believe the drug may also have a direct anti-inflammatory effect on joint tissue. More than one in eight participants ended the trial with no knee pain at all.
According to GoodRx, Eli Lilly expects to file for FDA approval in late 2026 or early 2027, with potential approval in 2027 or 2028. The drug is not currently available, and Drugs.com warns that any retatrutide sold by online vendors or compounding pharmacies is illegal.
