AT7687vsPemvidutide

AT7687 is a long-acting GIP receptor antagonist designed to reduce fat storage rather than suppress appetite — a fundamentally different mechanism from every other obesity drug currently on the market or in late-stage development. The rationale is grounded in human genetics: loss-of-function variants in the GIP receptor are associated with lower body mass index and reduced cardiometabolic risk, suggesting that pharmacologically blocking GIP signalling should reproduce these protective effects.

GIP (glucose-dependent insulinotropic polypeptide) normally functions as a fat-storage signal — released from intestinal K-cells in response to food intake, it instructs adipose tissue to take up and store circulating fatty acids. By blocking the GIP receptor specifically on adipocytes, AT7687 prevents this fat-storage signal from being transmitted, leading to reduced lipid uptake into fat cells and a metabolic shift favouring fat oxidation in muscle and liver. Because the mechanism does not depend on suppressing hunger or slowing gastric emptying, the gastrointestinal side effects that limit GLP-1 drug tolerability are largely absent.

This mechanism is the conceptual mirror of MariTide (which combines GLP-1 agonism with GIP antagonism in a single molecule) — AT7687 isolates the GIP-antagonist component to test whether it can produce meaningful weight loss alone or in future combination with GLP-1 agonists. Antag Therapeutics' first-in-human Phase 1 results in 2026 showed acceptable tolerability with mild GI symptoms, plus reductions in LDL cholesterol and resting heart rate — early signals consistent with the predicted cardiometabolic benefit profile. Phase 2 trials are expected to define the magnitude of weight loss achievable in obese patients.

Pemvidutide (ALT-801) is a once-weekly subcutaneous dual GLP-1 and glucagon receptor agonist, mechanistically similar to mazdutide and survodutide but with a distinct molecular design and a primary development focus on metabolic dysfunction-associated steatohepatitis (MASH) alongside obesity. The dual mechanism combines appetite suppression with enhanced energy expenditure and direct hepatic fat mobilisation.

The GLP-1 receptor component drives the established central appetite suppression through hypothalamic and brainstem signalling, slows gastric emptying, and stimulates glucose-dependent insulin secretion. The glucagon receptor agonism component is what differentiates pemvidutide from pure GLP-1 drugs — glucagon binding in hepatocytes activates adenylyl cyclase and protein kinase A, driving up fatty acid beta-oxidation and ketogenesis while reducing de novo lipogenesis. This directly mobilises stored hepatic triglycerides for energy use rather than continued storage, addressing the core pathology of MASH. In adipose tissue and beyond, glucagon signalling also raises whole-body energy expenditure through thermogenic and futile-cycle mechanisms.

The receptor potency ratio is balanced so that glucagon-driven hepatic glucose output is offset by GLP-1-driven insulinotropic effects, yielding net glycemic improvement alongside enhanced fat oxidation. Phase 2b results in obesity demonstrated approximately 15.6% mean body weight loss at 48 weeks, and parallel MASH trials showed significant reductions in liver fat content alongside improvements in fibrosis markers. Phase 3 trials in both obesity and MASH are now underway, positioning pemvidutide as Altimmune's lead asset and a competitor to mazdutide and survodutide in the dual GLP-1/glucagon class.