AT7687vsCagrilintide

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.

Cagrilintide is a long-acting analogue of amylin, a 37-amino-acid peptide hormone naturally co-secreted with insulin from pancreatic beta cells after meals. Native amylin plays a crucial but often overlooked role in metabolic regulation — it signals satiety, slows gastric emptying, and suppresses post-meal glucagon secretion through mechanisms entirely distinct from the GLP-1 pathway.

Cagrilintide activates amylin receptors, which are heterodimeric complexes formed by the calcitonin receptor (CTR) paired with receptor activity-modifying proteins (RAMP1, RAMP2, or RAMP3). These receptors are concentrated in the area postrema and the nucleus tractus solitarius in the brainstem — regions outside the blood-brain barrier that can directly sense circulating peptides. Activation of these neurons triggers ascending satiety signals to the hypothalamus, reducing meal size and food-seeking behavior through pathways that are neuroanatomically separate from GLP-1 signaling.

This distinct mechanism is why cagrilintide produces additive appetite suppression when combined with semaglutide (as CagriSema) — the two peptides target different populations of neurons within the brain's appetite control circuitry. Cagrilintide has been engineered with acylation modifications that enable albumin binding, extending its half-life from minutes (native amylin) to approximately one week, making it suitable for weekly subcutaneous dosing.