CagriSema is an investigational once-weekly injectable from Novo Nordisk that combines cagrilintide (an amylin analog) with semaglutide (a GLP-1 receptor agonist). Phase 3 REDEFINE trials showed roughly 20 to 22 percent weight loss in obesity and 13 to 15 percent with about 1.8 to 2.0 percent A1C reduction in type 2 diabetes. Regulatory submissions occurred in 2025 with possible approval in 2026.
What CagriSema Is
CagriSema is the working name for a fixed-dose combination of two drugs:
- Cagrilintide (2.4 mg) — a long-acting amylin analog. Amylin is a peptide co-secreted with insulin by pancreatic beta cells that slows gastric emptying, suppresses glucagon after meals, and reduces appetite.
- Semaglutide (2.4 mg) — the GLP-1 receptor agonist sold as Ozempic (T2D) and Wegovy (obesity).
The two are delivered in one once-weekly subcutaneous injection at matched doses. The development goal was to harness complementary appetite and glucose pathways for greater weight loss than either component alone.
How It Works
The two components target different but complementary pathways:
- GLP-1 (semaglutide): slows gastric emptying, glucose-dependent insulin release, glucagon suppression, central appetite reduction via hypothalamic circuits
- Amylin (cagrilintide): brainstem-mediated satiety signaling, additional gastric emptying delay, postmeal glucagon suppression
Stacking the two yields appetite suppression that exceeds either drug alone in early studies, with potentially smaller doses of each component contributing to tolerability.
REDEFINE Phase 3 Results
Novo Nordisk’s Phase 3 program has multiple trials. Headline data:
| Trial | Population | Duration | Weight loss | A1C reduction |
|---|---|---|---|---|
| REDEFINE-1 | Obesity without T2D | 68 weeks | ~20.4% | n/a |
| REDEFINE-2 | Obesity with T2D | 68 weeks | ~13-15% | ~1.8-2.0% |
| REDEFINE-3 | Obesity with established CV disease | Outcomes-based | Pending | Pending |
Earlier Phase 2 data had suggested weight loss of up to 17 percent in 32 weeks, leading some analysts to project Phase 3 numbers in the 25 percent range. The actual REDEFINE-1 result around 20 percent was strong in absolute terms but disappointed market expectations and contributed to revised commercial forecasts for the drug.
How CagriSema Compares
| Drug | Mechanism | Weight loss (obesity) | A1C (T2D) | Status (2026) |
|---|---|---|---|---|
| Semaglutide (Wegovy) | GLP-1 | ~15% | ~1.5% | FDA approved |
| Tirzepatide (Zepbound) | GLP-1 + GIP | ~21% | ~2.0% | FDA approved |
| CagriSema | GLP-1 + amylin | ~20-22% | ~1.8-2.0% | Filed for approval |
| Retatrutide | GLP-1 + GIP + glucagon | ~24% (Phase 2) | ~2.0%+ (Phase 2) | Investigational |
Side Effects
The Phase 3 safety profile is dominated by gastrointestinal effects similar to other incretin drugs, with possible amylin-related additions:
- Nausea — common, often during dose escalation
- Vomiting
- Diarrhea
- Constipation
- Abdominal pain or discomfort
- Decreased appetite
- Injection site reactions
- Mild fatigue
- Theoretical class concerns: pancreatitis, gallbladder events, medullary thyroid (rodent-based warning)
Discontinuation for adverse events in REDEFINE was approximately 5 to 8 percent at the full dose — comparable to semaglutide and tirzepatide in their pivotal obesity trials.
Dosing and Administration
- Once-weekly subcutaneous injection
- Single combination pen delivering both components at matched doses
- Dose escalation over 16 to 20 weeks to reach the target maintenance dose (2.4 mg / 2.4 mg)
- Injected in abdomen, thigh, or upper arm with rotation
Cardiovascular and Other Benefits
CagriSema is being studied in REDEFINE-3, a cardiovascular outcomes trial in adults with obesity and established cardiovascular disease — similar to the SELECT trial that supported a cardiovascular indication for semaglutide. Other studies are looking at metabolic dysfunction-associated steatohepatitis (MASH), heart failure with preserved ejection fraction, and kidney outcomes. Definitive results are pending.
Cost and Access Outlook
No US price is published as of mid-2026. By analogy to Wegovy and Zepbound, the list price is expected to be in the $1,300 to $1,500 monthly range before insurance and rebates. Insurance coverage in 2026 has expanded for obesity but remains inconsistent — many commercial plans cover it for type 2 diabetes; fewer cover it for obesity alone. Medicare coverage for obesity drugs is still limited. Compounded CagriSema is not legally available.
Who Might Be a Candidate If Approved
- Adults with obesity (BMI ≥30)
- Adults with overweight (BMI ≥27) plus a weight-related condition
- Adults with type 2 diabetes pursuing weight loss alongside glycemic control
- Patients with cardiovascular disease, pending REDEFINE-3 outcomes
Where It Fits Among Emerging Therapies
CagriSema is one of several next-generation injectable options being developed in parallel with retatrutide, orforglipron, and survodutide. For background on dietary and lifestyle complements, see diet and nutrition and the broader treatment overview. For glycemic targets, see A1C levels.
Open Questions
- Whether amylin component adds meaningful long-term durability versus GLP-1 alone
- Whether REDEFINE-3 confirms cardiovascular benefit comparable to or beyond semaglutide
- Whether the fixed-dose ratio is optimal for all populations
- How payer coverage compares with tirzepatide once both are on the market
- Pediatric data (not yet available)
What to Discuss with a Clinician
- Whether existing approved drugs (semaglutide, tirzepatide) have been tried
- Personal history of pancreatitis, gallbladder disease, or thyroid cancer
- Cardiovascular and kidney status
- Realistic weight-loss goals and willingness to maintain treatment long term
- Interest in clinical trial participation if commercial supply is delayed
The Bottom Line
CagriSema is an investigational once-weekly injectable combining the amylin analog cagrilintide with the GLP-1 receptor agonist semaglutide. In Phase 3 REDEFINE trials it produced about 20 to 22 percent weight loss in obesity and 13 to 15 percent with strong glycemic effects in type 2 diabetes — competitive with tirzepatide but somewhat below earlier expectations. Side effects are class-typical and mostly gastrointestinal. Novo Nordisk has filed for approval, with a potential FDA decision in 2026. Talk to your clinician about whether existing options fit your needs or whether clinical trials are appropriate while CagriSema completes regulatory review.
