Weight-Loss Drug Race Moves Beyond GLP-1s

AbbVie's specific candidate is ABBV-295, a long-acting amylin analog acquired through a partnership with Danish firm Gubra. The deal, initiated in March 2025, involved a $350 million upfront payment with potential for up to $2.3 billion in milestones, signaling a significant investment in non-incretin pathways. The Phase 1 trial showed that weekly doses led to a mean body-weight loss of up to 9.79% at 12 weeks, compared to a 0.26% loss in the placebo group. Amylin is a hormone co-secreted with insulin by the pancreas that contributes to satiety, slows gastric emptying, and suppresses the post-meal release of glucagon. This mechanism is distinct from GLP-1 agonists which primarily mimic an incretin gut hormone to regulate appetite and insulin. The strategic appeal of amylin analogs lies in potentially offering weight loss with a different and possibly more favorable side-effect profile, particularly concerning gastrointestinal issues. The pursuit of amylin-based therapies places AbbVie in direct competition with market leaders Novo Nordisk and Eli Lilly. Novo Nordisk is developing CagriSema, a combination of a GLP-1 and an amylin analog, as well as a standalone oral co-agonist called amycretin which showed a 13.1% weight loss in just 12 weeks in its own Phase 1 trial. Eli Lilly's amylin candidate, eloralintide, has already entered Phase 3 trials after demonstrating up to 20.1% weight loss at 48 weeks in a Phase 2 study. Beyond amylin, the industry is aggressively pursuing multi-agonist drugs. Eli Lilly's retatrutide, a "Triple G" agonist, targets GLP-1, GIP, and glucagon receptors. This triple-action mechanism is designed to also increase energy expenditure, and it produced a mean weight reduction of 24.2% after 48 weeks in a Phase 2 trial, setting a high benchmark for next-generation efficacy. Another key strategic vector is improving the quality of weight loss by preserving muscle mass, a known drawback of rapid weight loss from GLP-1s. Eli Lilly acquired Versanis to gain bimagrumab, a monoclonal antibody that blocks activin type II receptors to inhibit myostatin, thereby promoting lean mass while reducing fat. Amgen is also exploring novel approaches with MariTide, which combines a GLP-1 agonist with a GIP receptor *antagonist* to potentially improve tolerability. The intense R&D investment is driven by enormous market potential, with the global incretin market, which includes GLP