reviewed april 2026|next review october 2026|88 physicians psi has verified|7 published studies
CagriSema
CagriSema is an investigational fixed-dose combination of cagrilintide (a long-acting amylin analog) and semaglutide (a GLP-1 receptor agonist) in the REDEFINE Phase III program for obesity, targeting two independent appetite suppression pathways to produce weight loss superior to either component alone.
Evidence landscape: 7 published studies
Published studies span obesity pharmacology, amylin biology, and GLP-1 therapeutics. Phase II human data published. Phase III ongoing.
- 3 Animal
- 4 Reviews
Not FDA-approved. Phase III REDEFINE registrational trials are ongoing. Phase II data showed approximately 15-17% body weight reduction, superior to either cagrilintide or semaglutide alone. No regulatory submission has been made.
Not available outside clinical trials. CagriSema is being developed by Novo Nordisk. Commercial availability depends on Phase III results and regulatory approval.
CagriSema combines two validated mechanisms: amylin receptor agonism (validated by FDA-approved pramlintide/Symlin) and GLP-1 receptor agonism (validated by FDA-approved semaglutide/Ozempic/Wegovy). The combination targets independent appetite suppression pathways for additive or synergistic weight loss.
PSI Assessment
After GLP-1 drugs changed obesity treatment, the question became: what comes next? CagriSema represents one answer. It combines semaglutide (the active ingredient in Ozempic and Wegovy) with cagrilintide, a long-acting amylin analog that targets a second, independent appetite suppression pathway. Phase II data showed approximately 15-17% weight loss, superior to either component alone. The REDEFINE Phase III program is the largest active registrational obesity trial program. Both individual mechanisms are already validated by FDA-approved drugs.
Dual amylin/GLP-1 mechanism. Phase II showed 15-17% weight loss, superior to either component alone. REDEFINE Phase III ongoing. Both individual pathways are validated by FDA-approved drugs.
The mechanism combines two pharmacologically distinct appetite suppression pathways. Cagrilintide is a long-acting acylated amylin analog that binds AMY1 and AMY3 receptors, promoting satiety, slowing gastric emptying, and suppressing glucagon secretion. Semaglutide is a GLP-1 receptor agonist that reduces appetite, improves glucose homeostasis, and enhances beta cell function. The combination targets independent signaling pathways for additive metabolic improvement.
What the evidence supports
Phase II data demonstrated that the combination of cagrilintide and semaglutide produces approximately 15-17% body weight reduction, superior to either component alone. The dual amylin/GLP-1 mechanism is pharmacologically validated. The REDEFINE Phase III program is the largest active registrational obesity trial program. Both individual component mechanisms (amylin agonism and GLP-1 agonism) are validated by FDA-approved drugs (pramlintide for amylin, semaglutide for GLP-1).
What is not yet established
Phase III efficacy and safety from the REDEFINE program (results pending). Whether CagriSema achieves meaningfully greater weight loss than high-dose semaglutide alone. Long-term cardiovascular outcomes. Head-to-head comparison with tirzepatide. FDA approval.
Research Evidence
The findings below cover the Phase II combination data, the rationale for dual-mechanism targeting, and the REDEFINE Phase III program.
Evidence by condition
Evidence dimensions across obesity, type 2 diabetes, and cardiovascular outcome research. Phase II has the deepest published evidence. Phase III results pending.
| Condition | Mechanism | Animal evidence | Human evidence | Replication |
|---|---|---|---|---|
| Obesity | ||||
| Type 2 Diabetes | ||||
| Heart Failure |
Phase II data demonstrated that CagriSema produces approximately 15-17% body weight reduction over 32 weeks, significantly greater than either cagrilintide or semaglutide monotherapy.
The superiority over individual components validates the dual-mechanism hypothesis. Whether this advantage is maintained in larger Phase III populations and over longer treatment periods is being tested in REDEFINE.
Cagrilintide monotherapy dose-ranging studies established the amylin analog component as an independent appetite suppressant, with weight loss effects that are additive when combined with GLP-1 agonism.
The amylin pathway is validated by pramlintide (Symlin), which is FDA-approved for diabetes. Cagrilintide is a next-generation long-acting amylin analog designed for weekly injection.
The REDEFINE Phase III program includes trials in obesity, type 2 diabetes with obesity, and cardiovascular outcome assessment, representing the most comprehensive registrational program for a next-generation obesity drug.
Phase III results will determine whether CagriSema achieves regulatory approval. The program is designed to support a broad obesity indication, not just a niche population.
0 Human|3 Animal|4 Reviews
View all 7 indexed studiesHow CagriSema Works
CagriSema combines cagrilintide (long-acting amylin analog, AMY1/AMY3 receptor agonist) with semaglutide (GLP-1 receptor agonist) in a fixed-dose combination targeting two independent appetite suppression and metabolic improvement pathways.
CagriSema combines two appetite suppression pathways: amylin receptor agonism (cagrilintide) and GLP-1 receptor agonism (semaglutide). Amylin normally signals fullness after eating. GLP-1 regulates blood sugar and appetite. Targeting both simultaneously produces complementary appetite suppression and metabolic improvement.
For a more detailed view of the biology, here is what researchers have observed at the molecular level.
CagriSema combines cagrilintide (a long-acting amylin analog binding AMY1/AMY3 receptors) with semaglutide (a GLP-1 receptor agonist). Amylin receptor activation promotes satiety, slows gastric emptying, and suppresses glucagon. Combined with GLP-1 effects on appetite, glucose homeostasis, and beta cell function, the dual mechanism provides synergistic metabolic improvement.
What is CagriSema being studied for?
Researchers are studying CagriSema across several health conditions. Each condition below is labeled with the strength of evidence that exists for that specific use, not for CagriSema overall. This means a compound can have human studies for one condition but only animal data for another.
Obesity
·Human TrialsPhase II data showed 15-17% body weight reduction, superior to either component alone. REDEFINE Phase III registrational program is ongoing with the largest active enrollment in the obesity drug development landscape.
Limitations: Phase III results are pending. Whether the Phase II advantage over semaglutide monotherapy is maintained in larger populations and longer treatment periods is the key open question. Head-to-head comparison with tirzepatide has not been conducted.
Type 2 Diabetes
·Animal StudiesREDEFINE Phase III includes type 2 diabetes arms. The dual amylin/GLP-1 mechanism is expected to provide glycemic control in addition to weight loss.
Limitations: Dedicated type 2 diabetes Phase III data has not been published. The glycemic benefit is inferred from the individual component mechanisms.
Heart Failure
·PreclinicalCardiovascular outcome assessment is planned within the REDEFINE program. Weight loss magnitude suggests potential cardiovascular risk reduction.
Limitations: No cardiovascular outcome data exists. Cardiovascular benefit is theoretical based on weight loss magnitude and the semaglutide cardiovascular evidence base.
Safety and Regulatory Status
FDA Status: Not FDA-approved. Phase III REDEFINE registrational trials are ongoing. No regulatory submission has been made.
Availability: Available only through clinical trials. CagriSema is being developed by Novo Nordisk. Commercial timeline depends on Phase III results.
Class context: Phase II data showed gastrointestinal side effects (nausea, vomiting, diarrhea) consistent with incretin-based therapies. Both component mechanisms have established safety profiles from FDA-approved drugs (pramlintide for amylin, semaglutide for GLP-1). Long-term combination safety data is pending.
Side effects in Phase II were consistent with the GLP-1 and amylin drug classes: gastrointestinal symptoms (nausea, vomiting, diarrhea) that typically decrease over time. Long-term safety data from Phase III is pending.
Peptide Structure
Technical molecular data for researchers and clinicians.
Questions and Comparisons
Questions the evidence raises for a CagriSema discussion.
Comparison and Related Research
CagriSema is compared with other obesity drugs and next-generation weight loss therapies.
Related compounds
Frequently Asked Questions
References
Each citation links to the original study on PubMed, the U.S. National Library of Medicine database.
- 1.Pivotal Phase III trial of tesamorelin in 412 HIV-positive patients with excess abdominal fat. Over 26 weeks, tesamorelin significantly reduced visceral adipose tissue (VAT) by approximately 18% compared to placebo, with parallel improvements in trunk fat and patient-reported body image. This was the primary efficacy data supporting FDA approval for HIV-associated lipodystrophy.Falutz J et al., 2007 in N Engl J Med. View on PubMed
- 2.Pooled analysis of two Phase III trials including 816 HIV-infected patients with lipodystrophy. Tesamorelin reduced visceral fat by a mean of 15.2% versus a 5.0% increase with placebo. The treatment also improved triglyceride levels and reduced trunk fat-to-limb fat ratio without adversely affecting glucose homeostasis.Falutz J et al., 2010 in J Acquir Immune Defic Syndr. View on PubMed
- 3.Randomized trial examining tesamorelin's effects on both visceral fat and hepatic fat in HIV-infected patients. Tesamorelin reduced visceral adipose tissue by 14% and liver fat by approximately 37%, suggesting benefits beyond simple fat reduction, particularly for the elevated nonalcoholic fatty liver disease risk seen in this population.Stanley TL et al., 2014 in J Clin Endocrinol Metab. View on PubMed
- 4.Phase III trial with a 26-week safety extension in 273 patients. Visceral fat reductions achieved during the treatment phase were maintained during continued dosing but reversed upon discontinuation, demonstrating that ongoing treatment is needed to sustain the metabolic benefits.Falutz J et al., 2008 in J Clin Endocrinol Metab. View on PubMed
Medical Disclaimer
This content is for educational and informational purposes only and does not constitute medical advice. The information presented reflects published research as indexed by PSI and should not be used to make treatment decisions. Always consult a qualified healthcare provider before starting, stopping, or modifying any treatment.