Too much of a good thing?
Participants taking the highest dose of Eli Lilly’s new GLP-1 drug lost an average of 28.7% of their body weight in a late-stage trial, putting it on track to be a heavyweight in the crowded world of weight-loss and diabetes treatments.
But in a surprising twist, top-line results show higher dropout rates than in earlier trials, with at least some participants worried about just how slim they were becoming.
Participants in Eli Lilly’s retatrutide drug trial lost an average of 28.7% of their body weight — but for some, it was too effective. REUTERSLike Lilly’s other diabetes and obesity drugs, Mounjaro and Zepbound, retatrutide mimics GLP-1 and GIP, hormones the body produces naturally to curb appetite, slow digestion and lower blood sugar.
But this experimental drug goes a step further by adding a third hormone, glucagon, earning it the nickname “Triple G.”
In the Phase 3 “Triumph-4” trial, Lilly tested two doses of retatrutide against a placebo in 445 people who were obese or overweight and also had knee osteoarthritis.
After 68 weeks of once-weekly injections, patients who completed the higher 12 mg dose lost an average of 71.2 pounds. Those who finished the lower 9 mg dose lost 64.2 pounds on average, or 26.4% of their body weight.
That’s notably more than current weight-loss drugs on the market. For comparison, once-weekly injections of Lilly’s Zepbound have helped participants shed 15% to 21% of their starting weight after 72 weeks in clinical trials.
“This is beyond what we see with any other medication on the market, and it is what we see with some bariatric surgeries,” Dr. Jennah Siwak, an obesity medicine expert, said in a TikTok last December after the trial’s top-line results dropped. “This is insane.”
Retatrutide, nicknamed “Triple G,” targets three hormones in the body that affect appetite, slow digestion and lower blood sugar. dragonstock – stock.adobe.comBut not everyone made it to the finish line.
A whopping 18.2% of participants on the 12 mg dose dropped out due to adverse events, while 12.2% of those on the 9 mg dose left early. By comparison, just 4% of the placebo group quit before the study wrapped up.
For context, in a previous Phase 3 trial of Zepbound, the highest-dose group saw a dropout rate of only 6.2% due to adverse events.
The full data hasn’t been published yet, so it’s unclear why each patient left. Lilly noted, however, that dropouts were “highly correlated with baseline BMI and included discontinuations for perceived excessive weight loss.”
The company also pointed out that participants with a higher BMI were less likely to drop out.
Limiting the analysis to those with a BMI of 35 or higher brought dropout rates down to 8.8% for the low dose and 12.1% for the high dose, compared with 4.8% for the placebo — closer to the rates seen in Zepbound trials, but still higher.
“Our goal when developing obesity medicines is to help patients reach a place that feels healthy, comfortable and maintainable,” a spokesperson for Lilly told The Post.
“In our clinical trials, there are built‑in safeguards that allow physicians to slow down or step back dosing when medically appropriate, keeping patient safety front and center, and the resulting data are critical to help healthcare professionals make informed dosing decisions if a medicine is approved.”
Other side effects were reported in retatrutide patients as well. Dysesthesia, an unpleasant tingling or burning sensation in the skin, affected about 1 in 5 patients on the 12 mg dose and 1 in 13 on the 9 mg dose — though Lilly said most cases were mild and rarely caused participants to drop out.
Gastrointestinal issues were common, including diarrhea, constipation, vomiting and decreased appetite, which are often seen with GLP-1 drugs.
But retatrutide also showed some extra perks beyond its jaw-dropping weight-loss results. The experimental drug also appeared to ease knee pain, with both doses showing about a 75% drop in pain scores, compared with a 40% decline in the placebo group.
“People with obesity and knee osteoarthritis often live with pain and restricted mobility, and may eventually require total joint replacement,” Dr. Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health, said in a statement last year announcing the trial results.
“With seven additional Phase 3 readouts expected in 2026, we believe retatrutide could become an important option for patients with significant weight-loss needs and certain complications, including knee osteoarthritis.”
Start Your Weight Loss Journey
Hers makes getting a GLP-1 prescription for weight loss straightforward and approachable. Licensed providers create personalized treatment plans with ongoing medical support, offering options like custom compounds, injections, and pills.
BrightMeds makes accessing GLP-1 weight loss medications affordable and convenient with a straightforward subscription model. Patients receive personalized care and ongoing medical support, with treatment options designed for long-term weight management.
Ro offers simple and secure access to GLP-1 weight loss medications through its digital health platform. With personalized treatment plans, licensed provider support, and convenient home delivery, Ro makes clinically proven weight management more accessible.
