India Pharma Outlook Team | Tuesday, 22 September 2026
Novo Nordisk announced on September 21, 2026, that its investigational drug CagriSema outperformed Eli Lilly's tirzepatide in a head-to-head Phase 3 trial.
In the 68-week REIMAGINE 5 study, adults with type 2 diabetes on CagriSema 1.0 mg/1.0 mg lost 12.4 percent of their body weight, compared with 9.1 percent for those on tirzepatide 5 mg (branded as Mounjaro/Zepbound).
CagriSema combines two distinct hormonal pathways - semaglutide’s GLP-1 activity and cagrilintide’s amylin activity.
That reflects a broader shift in obesity drug development, as pharmaceutical companies increasingly move from single-pathway medicines toward combinations and multi-receptor therapies, designed to address the biology of weight regulation more comprehensively.
CagriSema is not a single molecule - it's a fixed-dose combination of two.
Combining the two allows Novo to attack appetite regulation from two directions at once rather than relying on GLP-1 alone.
Also Read: GLP-1 Side Effects: Tips for Gastrointestinal Comfort 2026 Update
Obesity drug development has moved in clear generational waves. Early options - orlistat, phentermine, and other appetite suppressants - delivered modest, single-digit weight loss.
GLP-1 monotherapies like Wegovy pushed that into the mid-teens. Tirzepatide then combined GLP-1 with a second gut hormone receptor, GIP, and posted even larger results in SURMOUNT-1.
CagriSema represents the next branch: instead of pairing GLP-1 with GIP, Novo paired it with amylin. It’s a structurally different combination chasing the same goal by a different biological route.
Earlier studies have also shown greater weight loss with the combination than with either component used alone, supporting the biological rationale for combining them.
Amylin acts largely in the brainstem, at appetite-regulating centers distinct from where GLP-1 predominantly signals, and it appears to preserve lean mass better in some early comparative data. A longstanding concern with GLP-1-class drugs, where a meaningful share of weight lost is muscle.
That's a large part of why multiple companies, not just Novo, are pursuing amylin analogues independently: Zealand Pharma and others have their own candidates in development.
Amylin is being explored both as a standalone therapy and in combination, because its mechanism may complement GLP-1 rather than duplicate it.
Also Read: 10 GLP-1 Drugs Revolutionizing Diabetes & Obesity Treatment
Tirzepatide already combines GIP and GLP-1 activity, while CagriSema combines GLP-1 and amylin. Eli Lilly is also developing retatrutide, a multi-receptor candidate targeting GIP, GLP-1 and glucagon pathways.
Other companies are pursuing amylin analogues, multi-hormone therapies and different molecular approaches.
Highlighting a broader R&D transition: the next generation of obesity medicines may increasingly be designed around multiple biological pathways rather than a single target.
.jpg)
