Lilly’s Eloralintide Shows 20% Weight Loss in Phase 2 Obesity Trial

Original posted at obesity.news/ on Dec 06, 2025

Most people spend Saturday night doing something normal. I spend mine reading amylin data, which feels about right for the kind of nerd I have turned into covering this space.

Lilly and Novo have been betting for years that amylin could become a serious pillar in their obesity strategies. In fact, Novo will likely submit Cagrisema in late 2026 for approval which combines Semaglutide with their own amylin agonist, Cagrilintide. The phase 2 readout for Eloralintide, however, finally gives us reason to believe that Lilly sees a real future in this obesity treatment pathway as well. The once weekly selective amylin receptor agonist produced up to 20% weight loss over 48 weeks in adults with obesity and no type 2 diabetes. For a monotherapy outside the GLP-1 family, the effect size is hard to ignore. This greatly outperforms data from Cagrilintide as a stand alone therapy, which saw around 12% at the highest dose after 68 weeks.

This trial enrolled 263 participants across 46 US sites. Mean age was 49. Mean baseline weight was 109 kg with a BMI of 39. Per the usual, the majority were women, in fact an astounding 78% of trial participants were women. Participants were randomized to 6 active dose arms or placebo, including 1 mg, 3 mg, 6 mg, 9 mg and 2 escalation paths reaching the higher levels. Lilly funded the study under its shared master protocol used for multiple obesity programs.

The weight loss signal followed a clean dose response.

1 mg achieved 9%.

3 mg reached 12%.

6 mg hit 18%.

9 mg and the high range escalation arm delivered 20%.

Placebo declined 0.4%.

The weight curves were still trending downward at week 48, which suggests the ceiling may sit beyond the current study window.

Tolerability aligned with the mechanism. Nausea was the most common adverse event and increased with dose. Fatigue showed the same dose relationship. Most events were mild or moderate. The overall safety profile does not show an obvious hurdle for advancement, and the selectivity engineered into the molecule appears to be accomplishing its intended effect.

Mechanistically, Eloralintide binds the human AMY1 receptor with 12× greater potency than the calcitonin receptor. The molecule includes a C20 fatty diacid to support albumin binding and extend half life for weekly administration. Phase 1 work showed up to 11% loss at 12 weeks. This study provided the first clear look at long term durability.

The defining takeaway is that the monotherapy signal is much stronger than prior amylin agents. Historically, this class has been treated as a supporting player or a combination partner for GLP-1 therapies. While cagrilintide offered early validation that amylin could operate as a primary mechanism. Eloralintide pushes that validation further with tighter selectivity and higher potency.

Secondary markers moved in the expected direction. Lipids improved. High sensitivity CRP decreased. These findings will matter as the program broadens into populations with cardiometabolic risk.

The strategic question now is where Lilly intends to position Eloralintide inside an already full obesity pipeline. The company has oral incretins, fixed ratio combinations, long acting next generation GLP-1 assets and several early phase programs. A selective amylin agent with a 20% monotherapy profile gives Lilly a differentiated entry point that does not rely on incretin receptor engagement and may appeal to patients who cannot tolerate GLP-1 or GIP therapies.

Lilly has not disclosed phase 3 timelines, but the strength of the signal makes the next step predictable. Combination trials with GLP-1 agents will draw attention across the field. If these results hold in larger studies, Eloralintide could become a legitimate second pillar in obesity medicine and a competitive asset for Lilly in a market with growing pressure on incretin pricing and coverage.

This all begs the REAL question… Who else is reading about future obesity medicine on a Saturday? That’s why I love our substack community… You all are my people!

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