Eli Lilly (LLY) : retatrutide

Eli Lilly's next-generation obesity drug, retatrutide (a triple agonist targeting GIP, GLP-1, and glucagon receptors), has shown record-breaking weight loss results in Phase 3 trials.

Key Results from Recent Trials

• TRIUMPH-4 (obesity + knee osteoarthritis, Dec 2025): In a 68-week study, the highest dose (12 mg) led to an average 28.7% body weight loss (about 71.2 lbs / 32 kg from a baseline of ~248 lbs) among those who stayed on treatment. Including dropouts, it was around 23.7%. It also significantly reduced knee pain (up to 75.8% improvement on WOMAC scores).
• TRIUMPH-1 (general obesity/overweight with comorbidities, May 2026): Highest dose achieved ~28.3% weight loss over 80 weeks. Over 45% of participants lost 30%+ of body weight, and many reached a BMI under 30. This puts it in bariatric surgery territory for many patients.
• Diabetes trial (TRANSCEND-T2D-1, Mar 2026): Strong A1C reductions (1.7–2.0%) plus up to ~16.8% weight loss (36.6 lbs) at 40 weeks, with weight loss still ongoing.

These results outperform current blockbusters like Zepbound (tirzepatide, dual GIP/GLP-1, typically ~15–22% weight loss) and Wegovy (semaglutide, ~15–20%). Retatrutide's addition of glucagon receptor agonism appears to boost fat burning and energy expenditure.Side Effects and TolerabilityGastrointestinal issues (nausea, etc.) are common, similar to other incretins, with rates up to ~42%. Discontinuation rates were notably higher than in earlier trials—some participants stopped due to perceived excessive weight loss or skin-related side effects. This is a key watchpoint for real-world use.Context and OutlookRetatrutide is part of Lilly's deep obesity pipeline (alongside the oral GLP-1 orforglipron and others like eloralintide). Regulatory filings are expected later in 2026, with potential approval/launch in 2027.These "eye-popping" results highlight rapid progress in multi-agonist drugs, but questions remain around long-term safety, muscle preservation, maintenance after stopping, and broad accessibility/cost.