Eloralintide is a new peptide that mainly hits the AMY1R receptor, causing less nausea than older drugs like cagrilintide. In obese rats it cut food intake and dropped body weight (mostly fat) in a dose‑dependent way. In a small human safety study, a single weekly dose of 4 mg cut weight by about 2.5% after four weeks and 12 mg cut it by about 4%, with only mild stomach side effects, suggesting it could be taken once a week for weight control.

Eloralintide (LY3841136), a novel amylin analog, was evaluated in translational studies to characterize its therapeutic potential for treating obesity. In vitro assays were performed in cell lines selectively expressing rat or human amylin 1 receptor (AMY1R), amylin 3 receptor (AMY3R), or calcitonin receptor (CTR). In vivo studies were conducted in rats and monkeys. A phase 1, randomized, placebo-controlled, participant/investigator-blinded trial evaluated the safety and tolerability of single-ascending eloralintide doses (0.04-12 mg) in healthy participants (NCT05295940). In vitro, eloralintide preferentially activated human AMY1R (12-fold > CTR, 11-fold > AMY3R), while in rats, both AMY1R and AMY3R were activated more potently than CTR. Eloralintide induced significantly less conditioned taste avoidance in lean rats than cagrilintide, a non-selective amylin receptor agonist (p < 0.05). Eloralintide dose dependently reduced food intake and lowered body weight, primarily through fat mass loss, in diet-induced obese rats. Eloralintide demonstrated favorable pharmacokinetics in both rats and monkeys. In the phase 1 trial, 48 healthy participants had a mean body mass index of 27.5 kg/m². Nine participants in the eloralintide cohorts reported 16 adverse events, with most being mild (n = 15/16). Two participants reported 4 gastrointestinal events, including one moderate vomiting event. The pharmacokinetic profile of eloralintide supports once-weekly dosing. In eloralintide cohorts receiving single doses of 4 or 12 mg, week-4 mean percent change from baseline in body weight was -2.5% (p < 0.01) and -4.4% (p < 0.001), respectively, vs placebo (+0.6%). Once-weekly dosing with eloralintide, an AMY1R-selective agonist, may offer a promising new therapeutic with favorable gastrointestinal tolerability for the treatment of obesity.