The news: The latest study for Eli Lilly’s “triple-G” obesity drug retratrutide (which targets GLP-1, GIP, and glucagon) showed significant weight loss in patients with diabetes—who are typically more resistant to weight loss on GLP-1s.

• Patients with type 2 diabetes lost up to 15.3% of their body weight after 40 weeks, with no plateau—suggesting further weight loss is possible.
• Patients’ blood sugar levels also decreased by 1.9 percentage points. These results are similar to Lilly’s already approved Mounjaro, which resulted in an average 1.8 percentage point decline in blood sugar levels.
• Lilly is expected to submit retratrutide to the FDA for obesity approval by the end of the year, followed by a filing for type 2 diabetes in 2027.

Why it matters: Lilly’s next-generation drug is leading in clinical results among emerging GLP-1 treatments. It’s expected to extend Lilly’s lead in diabetes treatments with Mounjaro and in obesity with Zepbound. Lilly is also studying the drug for conditions including knee osteoarthritis, sleep apnea, and cardiovascular and liver diseases. Early data are promising. In knee osteoarthritis, for example, retratrutide reduced pain by up to 75.8% per the December study.

But retratrutide is also raising concerns about adverse side effects and excessive weight loss.

• A December study of only obese patients showed even more weight loss, an average 28.7% of their body weight. That’s well above the average weight loss of up to 20.9% for Zepbound and 20.7% for Novo Nordisk’s newly approved high-dose Wegovy HD, raising concerns about inadequate food intake and disordered eating.
• In the new study, 5.1% of patients discontinued use because of adverse side effects—on par with Zepbound’s 5 % to 7% drop outs.
• But in an earlier obesity study, up to 18% of retratrutide patients stopped taking the drug because of adverse events, which included “perceived excessive weight loss,” per Lilly.

Implications for pharma GLP-1 drugmakers: Lilly’s latest data raises the bar for what’s possible for people with diabetes who are also overweight—which is about 60% of US adults (those with type 2 diabetes). The results also mean drugmakers in this space will need to take more responsibility for defining appropriate weight loss limits.

Pharma companies must give clear BMI guidelines, add guardrails for non-obese patients, and closely monitor when treatment should be paused. They’ll also need to invest in education beyond weight loss metrics, such as guidance for healthcare providers on dosing adjustments and consumer marketing that emphasizes realistic, health-based outcomes.

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