Recall(New to the series?)
The drugs in this post don't all fit the GLP-1/GIP/glucagon receptor framework — some use amylin co-agonism, some invert the GIP approach, some push dosing to monthly or quarterly. For the foundational receptor context, see The Receptor Game.
The single → dual → triple agonist progression is the main trunk. This family is the branches: drugs that add mechanistically distinct pathways, invert the expected GIP effect, push dosing intervals far past weekly, or offer an entirely separate mechanism for patients who can't tolerate GLP-1 drugs.
Three different bets
Combination pathways — CagriSema adds amylin to semaglutide, activating a separate brainstem satiety circuit alongside GLP-1's hypothalamic one. Petrelintide offers pure amylin-pathway agonism with no GLP-1R involvement, for patients who can't tolerate GLP-1 at all.
Dosing interval — MariTide (monthly antibody conjugate) and ASC30 (monthly→quarterly injectable) are tackling the maintenance adherence problem. Same or similar efficacy, dramatically longer dosing intervals. A quarterly injection changes the real-world treatment experience significantly.
Receptor inversion — MariTide antagonizes GIPR rather than agonizing it, the opposite of tirzepatide. It's a bet that the old theory about GIP opposing weight loss was right in a different context, or that GIPR blockade plus GLP-1R agonism produces a useful distinct profile.
Drugs in this family
- CagriSema — Novo Nordisk, Phase 3, ~22.7% weight loss (REDEFINE 1)
- MariTide — Amgen, Phase 3, monthly injection, GIP antagonist
- ASC30 — Ascletis, Phase 2, monthly→quarterly dosing
- Petrelintide — Zealand/Roche, Phase 2, amylin-only pathway
Summary(The emerging modalities picture)
CagriSema is the nearest to approval with Phase 3 data at ~22.7%. MariTide's monthly dosing is the most commercially differentiated format if efficacy holds. Petrelintide serves a distinct patient population with no other pharmacological option. ASC30 is the longest duration bet. All are Phase 2–3; the field is watching to see which of these structural experiments survive into approval.