Participants Drop Out of Eli Lilly's New Weight Loss Drug Trial Due to Excessive Weight Loss

The experimental 'Triple G' drug retatrutide led to an average 28.7% weight loss, but some participants left the study over concerns about becoming too slim.

Published on Feb. 21, 2026

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Participants taking the highest dose of Eli Lilly's new GLP-1 drug retatrutide lost an average of 28.7% of their body weight in a late-stage trial, putting it on track to be a major player in the weight-loss and diabetes treatment market. However, the trial saw higher dropout rates than previous studies, with some participants concerned about the extent of their weight loss.

Why it matters

Retatrutide's impressive weight-loss results could make it a breakthrough treatment, but the high dropout rate due to excessive weight loss raises questions about the drug's safety and tolerability, especially at the highest doses. This highlights the need to balance efficacy and side effects when developing new obesity medications.

The details

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, patients who completed the higher 12mg dose lost an average of 71.2 pounds, while those on the lower 9mg dose lost 64.2 pounds on average. However, a whopping 18.2% of participants on the 12mg dose dropped out due to adverse events, compared to just 4% in the placebo group. Lilly noted the dropouts were 'highly correlated with baseline BMI and included discontinuations for perceived excessive weight loss.' The company said participants with a higher BMI were less likely to drop out.

  • The Phase 3 'Triumph-4' trial lasted 68 weeks.
  • Lilly expects seven additional Phase 3 readouts for retatrutide in 2026.

The players

Eli Lilly

A pharmaceutical company that developed the experimental weight-loss drug retatrutide.

Retatrutide

Eli Lilly's new GLP-1 drug that targets three hormones to curb appetite, slow digestion, and lower blood sugar. It is nicknamed the 'Triple G' drug.

Dr. Jennah Siwak

An obesity medicine expert who commented on the trial results in a TikTok video.

Dr. Kenneth Custer

The executive vice president and president of Lilly Cardiometabolic Health, who commented on the potential benefits of retatrutide for patients with obesity and knee osteoarthritis.

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What they’re saying

“This is beyond what we see with any other medication on the market, and it is what we see with some bariatric surgeries. This is insane.”

— Dr. Jennah Siwak, Obesity medicine expert (TikTok)

“People with obesity and knee osteoarthritis often live with pain and restricted mobility, and may eventually require total joint replacement. 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.”

— Dr. Kenneth Custer, Executive Vice President and President of Lilly Cardiometabolic Health (Eli Lilly statement)

What’s next

The full data from the Triumph-4 trial has not been published yet, so more details on the reasons for the high dropout rates are still to come. Lilly expects to have seven additional Phase 3 readouts for retatrutide in 2026, which will provide more insight into the drug's safety and efficacy.

The takeaway

Retatrutide's impressive weight-loss results demonstrate the potential of new obesity medications, but the high dropout rate due to excessive weight loss highlights the need to carefully balance efficacy and side effects. As Lilly continues to develop retatrutide, they will need to address concerns about tolerability, especially at the highest doses, to ensure the drug can be a safe and effective option for patients struggling with obesity and related conditions.