What’s next in obesity pharmacotherapy?

The next wave of obesity drugs could address several persistent gaps in treatment: insufficient weight loss, weekly injection burden, and obesity-related liver disease. From dual- and triple-hormone therapies approaching bariatric surgery–level weight loss to a once-monthly injection and an oral drug with early injectable-like efficacy, these five pipeline agents could expand how clinicians individualize obesity treatment.

CagriSema

Dual-pathway appetite targeting

CagriSema combines semaglutide with cagrilintide, an amylin analog, as a once-weekly subcutaneous injection. In the phase 3a REDEFINE 1 trial, which enrolled adults without diabetes who had obesity or overweight with at least one obesity-related complication, estimated mean weight loss at 68 weeks was 20.4% with CagriSema versus 14.9% with semaglutide alone. Overall, 34.7% of CagriSema recipients achieved at least 25% weight loss. In December 2025, Novo Nordisk submitted a new drug application to the FDA for CagriSema as a chronic weight-management treatment.

Why it matters: Some patients do not achieve sufficient weight loss with GLP-1 therapy alone to substantially improve obesity-related complications. By adding complementary amylin signaling, CagriSema could help more patients reach higher weight-loss thresholds while retaining once-weekly dosing.

Retatrutide

Triple-hormone therapy approaches surgical-level weight loss

Retatrutide is the first investigational therapy to activate GIP, GLP-1, and glucagon receptors. The glucagon component is intended to increase energy expenditure and fat oxidation in addition to reducing appetite. In the phase 3 TRIUMPH-1 trial, the 12 mg dose produced 28.3% mean weight loss at 80 weeks, increasing to 30.3% at 104 weeks among patients with severe obesity. Retatrutide has also produced substantial reductions in liver fat.

Why it matters: Retatrutide could narrow the efficacy gap between medication and bariatric surgery, potentially changing when clinicians discuss pharmacotherapy versus procedural treatment. Its effects on liver fat may make it particularly relevant for patients with obesity and coexisting metabolic dysfunction–associated steatohepatitis (MASH).

Survodutide

Obesity treatment with a liver-metabolic focus

Survodutide combines GLP-1 and glucagon receptor agonism without targeting GIP. In the phase 3 SYNCHRONIZE-1 trial, it produced up to 13% weight loss at 76 weeks. A substudy found a 63% reduction in liver fat and a 34% reduction in visceral fat. Weight loss had not plateaued by the end of the study.

Why it matters: Survodutide may not produce as much weight loss as some competing pipeline therapies, but its effects on liver and visceral fat could distinguish it for patients with obesity complicated by metabolic liver disease. It may shift treatment selection toward matching a drug’s metabolic effects to a patient’s predominant comorbidities rather than focusing on body weight alone.

MariTide

Once-monthly obesity treatment

Maridebart cafraglutide, or MariTide, combines GLP-1 receptor agonism with GIP receptor antagonism—taking a different approach to GIP signaling than tirzepatide. Its approximately 21-day half-life permits once-monthly or potentially less frequent dosing. In a phase 2 trial, MariTide produced up to 16.2% weight loss at 52 weeks, with much of the effect maintained for as long as 150 days after the final dose. Phase 3 trials are ongoing.

Why it matters: Less-frequent dosing could reduce treatment burden and make long-term therapy easier for patients who struggle with weekly injections. Its prolonged activity may also help preserve benefit when doses are delayed, although clinicians will need to consider how the long half-life affects titration and management of adverse effects.

Zenagamtide (formerly amycretin)

GLP-1 and amylin activity in one molecule

Where CagriSema combines two drugs, zenagamtide integrates GLP-1 and amylin receptor agonism into a single molecule being developed in both subcutaneous and oral formulations. Early trials found up to 24.3% weight loss at 36 weeks with subcutaneous zenagamtide, while the oral formulation produced approximately 13% weight loss after 12 weeks. These findings come from small, early-phase studies and require confirmation. The subcutaneous formulation has advanced into phase 3, while oral zenagamtide remains in phase 2 development.

Why it matters: The oral formulation is zenagamtide’s key potential differentiator. If ongoing clinical development confirms longer-term efficacy and tolerability, it could provide substantial weight loss without injections and expand treatment choices for patients who prefer an oral option.