Lilly's amylin-tirzepatide combo hits 23% weight loss in Phase 2 trial

Key points

• The combination regimen of eloralintide and tirzepatide achieved an average weight loss of 23.3% (54 pounds) at the highest dose over 48 weeks.
• This result exceeded the 14.8% weight loss seen with tirzepatide alone and the 12.3% seen with eloralintide alone in the same trial.
• The therapy also lowered blood sugar levels (A1C) by up to 2.9%, compared to 2.4% for tirzepatide alone.
• Discontinuation rates due to side effects were higher for the combination (10.8% to 27%) than for tirzepatide alone (2.9%), though most side effects were mild gastrointestinal issues.
• Lilly intends to begin Phase 3 trials for the combination, including a single-injection co-formulation, by the end of 2026.

Background

Eli Lilly has been aggressively expanding its obesity drug pipeline beyond its current blockbuster, tirzepatide (sold as Zepbound and Mounjaro). Recent archive coverage highlights the company's other next-generation candidate, retatrutide, which targets three hormones and has already shown record-breaking weight loss of up to 25% in Phase 3 trials. The current amylin-tirzepatide combination represents a different strategic approach, aiming to combine two existing or near-existing mechanisms to capture patients who do not respond adequately to single-drug therapies. This follows a broader industry trend of testing multi-hormone agonists to improve efficacy and tolerability.

How outlets are covering it

CNBC emphasized the potential of the combination to serve as a 'winning approach' for patients who do not achieve desired results with current GLP-1 products, highlighting the physiological benefit of engaging three hormone systems. STAT focused on the clinical efficacy but raised concerns about the high discontinuation rates, noting that patients with diabetes typically struggle to lose weight and that tolerability remains a key question. Yahoo's coverage was limited to the headline, confirming the significant results but noting the lack of FDA approval. Analysts cited by CNBC, such as David Risinger, viewed the amylin drug as having 'mega-blockbuster' potential, while others compared the strategy to Novo Nordisk's CagriSema.

Why it matters

The success of this combination could provide a critical alternative for the millions of patients who do not respond adequately to current GLP-1 therapies like tirzepatide or semaglutide. By targeting amylin in addition to GLP-1 and GIP, Lilly aims to enhance satiety and weight loss without necessarily increasing the intensity of a single hormone pathway. This could expand the market for obesity treatments and intensify competition with Novo Nordisk's next-generation drugs. However, the higher side effect rates must be managed in Phase 3 trials to ensure the drug is viable for long-term use.

What to watch

Eli Lilly plans to initiate Phase 3 trials for the eloralintide-tirzepatide combination by the end of 2026. These trials will likely include a co-formulation that allows patients to take a single injection containing both drugs. The company expects to adjust dosing regimens to improve the balance between efficacy and tolerability, addressing the higher discontinuation rates observed in the Phase 2 trial. Results from these late-stage studies will determine if the combination becomes a viable blockbuster treatment option.