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CagriSema

From PeptidePlaza, the free peptide reference · Entry #032 · Peptide Blends · Hand-curated entry · Editorial standards

Research warning. Research chemical — not for human consumption. Combining two potent satiety agents produces additive gastrointestinal toxicity and additive hypoglycaemia risk when insulin secretagogues are present. Class warnings from both components apply, including the rodent thyroid C-cell tumour signal for semaglutide.

CagriSema (also known as Cagrilintide-semaglutide, NN9838 + semaglutide, CagriSema 2.4/2.4) is a peptide blends research peptide. The first amylin + GLP-1 fixed-dose combination to reach phase 3. Two satiety systems in one weekly injection, and the closest any injectable has come to bariatric-surgery-range weight loss.

CagriSema is a co-formulation of cagrilintide (long-acting amylin analogue) and semaglutide (GLP-1 receptor agonist) at 2.4 mg each, given as a single weekly subcutaneous injection. The rationale is mechanistic: amylin and GLP-1 converge on satiation but through partly independent circuits — amylin acting on the area postrema and reward pathways, GLP-1 on hypothalamic and brainstem appetite regulation plus incretin effects — so the combination produces greater weight loss than either component. In REDEFINE 1 (N=3,417, 68 weeks, adults with overweight/obesity without diabetes), CagriSema produced a mean weight reduction of approximately 20.4% vs 3.0% for placebo, with 14.9% for semaglutide alone and 11.5% for cagrilintide alone. Under the trial-product estimand (i.e. full adherence), reduction reached 22.7%, with 40.4% of participants losing at least 25% of body weight. In REDEFINE 2 (N=1,206, type 2 diabetes) weight reduction was 13.7% vs 3.4% for placebo, and 74% of participants achieved HbA1c ≤6.5%. Gastrointestinal adverse events were common (approximately 80% vs 40% placebo) but predominantly mild to moderate and transient.

1 Mechanism of action

Dual satiety-pathway activation: semaglutide agonises GLP-1 receptors (hypothalamus, brainstem, pancreatic β-cells, gut) while cagrilintide agonises amylin and calcitonin receptors in the area postrema. The result is additive suppression of energy intake plus incretin-mediated glycaemic improvement and slowed gastric emptying from both components.

Primary targets: GLP-1R · AMY1 · AMY2 · AMY3 · Calcitonin receptor (CTR)

2 Reported effects

Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.

2.1 Reported benefits

  • ~20.4% mean weight reduction at 68 weeks (22.7% under full adherence)
  • 40.4% of adherent participants lost ≥25% of body weight
  • 88% of participants with prediabetes returned to normoglycaemia
  • Improvements in systolic blood pressure, waist circumference and lipid profile
  • 74% of participants with type 2 diabetes achieved HbA1c ≤6.5% (REDEFINE 2)
  • Single weekly injection despite being a two-component regimen

2.2 Side effects

  • Gastrointestinal adverse events in ~80% of participants (nausea, vomiting, diarrhoea)
  • Higher discontinuation rate than either monotherapy
  • Appetite suppression severe enough to risk inadequate protein and micronutrient intake
  • Injection site reactions
  • Gallbladder-related events associated with rapid weight loss
  • Loss of lean body mass during rapid weight reduction

3 Chemical and physical properties

Purity (typical)>98% (each component)
Half-life~7 days (both components; single weekly injection)
Storage−20 °C, lyophilised powder, desiccated
SolubilitySterile water / bacteriostatic water
Receptors / targetsGLP-1R, AMY1, AMY2, AMY3, Calcitonin receptor (CTR)

4 Research dosages

Phase 3 protocol: co-titration to 2.4 mg cagrilintide + 2.4 mg semaglutide SC once weekly over a 16–20 week escalation.

Dosages are reported from published protocols for reference only. Research chemicals are not for human consumption.

5 Research studies (8)

  1. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)
    New England Journal of Medicine (2025) · RCT · N=3,417
    68-week phase 3 RCT comparing CagriSema, each monotherapy, and placebo in adults with overweight or obesity without diabetes.
    Key finding: ~20.4% mean weight reduction vs 3.0% placebo (22.7% under the trial-product estimand); 40.4% of adherent participants lost ≥25% of body weight.
  2. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2)
    New England Journal of Medicine (2025) · RCT · N=1,206
    Phase 3 RCT in adults with type 2 diabetes and overweight/obesity over 68 weeks.
    Key finding: 13.7% weight reduction vs 3.4% with placebo; 74% reached HbA1c ≤6.5% vs 15.9% on placebo.
  3. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.
    The New England journal of medicine (2025) · RCT
    Cagrilintide-semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, as compared with placebo.
  4. The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines.
    Expert opinion on investigational drugs (2025) · Review
    GLP-1-based therapies have changed the treatment of overweight/obesity.
  5. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.
    The New England journal of medicine (2025) · RCT
    Once-weekly cagrilintide-semaglutide (at a dose of 2.4 mg each) resulted in a significantly lower body weight than placebo in adults with obesity and type 2 diabetes.
  6. What is the pipeline for future medications for obesity?.
    International journal of obesity (2005) (2025) · Review
    Obesity is a chronic disease associated with increased risk of obesity-related complications and mortality.
  7. Emerging pharmacotherapies for obesity: A systematic review.
    Pharmacological reviews (2025) · Systematic Review
    The history of antiobesity pharmacotherapies is marked by disappointments, often entangled with societal pressure promoting weight loss and the prevailing conviction that excess body weight signifies a lack of...
  8. Weight management treatment in obesity.
    Medicina clinica (2025) · Review
    Obesity is a chronic and relapsing disease associated with medical complications and mortality.

6 Safety and risk profile

6.1 Regulatory status

CagriSema is currently classified as Phase 3 clinical trials. It has no approved human indication in the United States; availability elsewhere does not imply demonstrated safety or efficacy.

Safety score: 70/100 — low concern. Derived from clinical data volume, known risks and regulatory status.

6.2 Contraindications

Conditions and populations in which use is contraindicated:

  • Personal or family history of medullary thyroid carcinoma or MEN2
  • History of pancreatitis
  • Severe gastroparesis or gastrointestinal motility disorder
  • Pregnancy or lactation
  • Type 1 diabetes mellitus
  • Known hypersensitivity to either component

6.3 Drug interactions

Drug or classInteractionRisk
Insulin / sulfonylureasSubstantial additive hypoglycaemia risk from both components — secretagogue doses generally need reduction.High
Oral medications (narrow therapeutic index)Two agents delaying gastric emptying compound absorption changes — levothyroxine, anticoagulants and anticonvulsants warrant monitoring.Moderate
Other appetite suppressantsAdditive anorexia and dehydration risk; no data supporting triple combinations.Moderate

6.4 Long-term risks

  • No data beyond the 68-week trial horizon for the combination
  • Sarcopenia risk from very rapid weight loss without resistance training and protein intake
  • Nutritional deficiency with sustained profound appetite suppression
  • Weight regain on discontinuation, consistent with the GLP-1 class
  • Gallstone formation associated with rapid weight reduction

6.5 Research best practices

  • Store both components at 2–8 °C once reconstituted; lyophilised material at −20 °C
  • Escalate over 16+ weeks — GI tolerability is driven by rate of escalation
  • Track lean mass, not just total weight, in any protocol
  • Maintain protein intake and resistance loading to blunt lean-mass loss
  • Monitor gallbladder and pancreatic markers during rapid weight reduction
Safety data disclaimer. Safety assessments are based on published literature and are for educational reference only. Clinical evidence varies significantly between peptides. Always consult primary research and current regulatory guidance.

7 Frequently asked questions

Is CagriSema better than tirzepatide?
No head-to-head trial has been published. REDEFINE 1 reported ~20.4% mean weight loss (22.7% with full adherence) at 68 weeks, and SURMOUNT-1 reported 22.5% for tirzepatide 15 mg at 72 weeks — the trials differ in design, population and duration, so cross-trial comparison is unreliable.
Why combine amylin with GLP-1 instead of raising the GLP-1 dose?
GLP-1 monotherapy plateaus: higher doses mostly buy more nausea rather than more weight loss. Adding a second, partly independent satiety mechanism raises the ceiling without simply escalating GLP-1 receptor occupancy.
What did the gastrointestinal side effect profile look like?
Roughly 80% of CagriSema participants reported GI adverse events vs 40% on placebo — nausea, vomiting and diarrhoea predominantly, mostly mild to moderate and concentrated in the escalation phase.

8 References

  1. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. PubMed (2025). Garvey WT, et al.. View source
  2. The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines. PubMed (2025). Madsbad S, et al.. View source
  3. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. PubMed (2025). Davies MJ, et al.. View source
  4. What is the pipeline for future medications for obesity?. PubMed (2025). Melson E, et al.. View source

Related compounds

Entries that share a target, a mechanism, or a research area with CagriSema.

Liraglutideapproved

Also targets GLP-1R

The GLP-1 that proved the class. A C16 palmitoyl chain gave native GLP-1 a 13-hour half-life instead of two minutes — and produced the first cardiovascular outcome data for the family.

Semaglutideapproved

Also targets GLP-1R

A long-acting GLP-1 analog distinguished by its C18 fatty diacid chain, enabling albumin binding and a half-life of ~7 days. One of the most clinically studied peptides in modern metabolic research.

Cagrilintidemetabolic

Also targets AMY1

A lipidated amylin analogue engineered to resist the amyloid fibrillation that plagues native human amylin. Works on satiety pathways entirely separate from GLP-1 — which is why it stacks so effectively with semaglutide.

Survodutidemetabolic

Also targets GLP-1R

A 29-amino-acid dual agonist that pairs GLP-1 appetite suppression with glucagon-driven energy expenditure and hepatic fat oxidation. Its liver-fat data is the standout: up to 63% reduction.

Mazdutidemetabolic

Also targets GLP-1R

An oxyntomodulin-based dual agonist and the first GLP-1/glucagon co-agonist approved anywhere in the world — cleared in China for weight management in 2025.

Retatrutidemetabolic

Also targets GLP-1R

A novel triple receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously — the first of its kind in human Phase 2 trials. Early data suggests it may surpass dual agonists.

9 See also

For research reference only. Not medical advice. Peptides may be regulated or restricted in your jurisdiction. Entry validated by the PeptidePlaza Biomedical Research Desk; see editorial standards.