CagriSema: research
An unapproved cagrilintide–semaglutide combination with phase 3 weight-loss and diabetes results.
Also called: Cagrilintide/semaglutide, Cagrilintide-semaglutide, CagriSema 2.4 mg/2.4 mg.
Amylin analogues · Combination of an amylin analogue and a GLP-1 receptor agonist.
33 unique registered combination studies plus one simulated-use pen study. Includes ongoing/unreported records; reviews and secondary analyses are not new trials.
Studies
- Phase 1b: six combination doses. rct, n=96, Otherwise healthy adults aged 18–55 with BMI 27–39.9. Early combination testing supported weekly dosing and further trials. (source)
- Combined versus separate injections. rct, n=40, Age 18 Years to 55 Years; Obesity & Overweight. Status: completed. No clinical benefit is established by registration. (source)
- Phase 2: combination versus each drug. rct, n=92, Adults with type 2 diabetes and BMI ≥27 on metformin, with or without an SGLT2 inhibitor. The combination added weight loss; its HbA1c advantage over semaglutide was not significant. (source)
- MASH trial: exploratory CagriSema arm. rct, n=698, Adults with biopsy-confirmed MASH and F2–F4 compensated fibrosis. This exploratory combination arm did not establish a liver-fibrosis benefit. (source)
- REDEFINE 2: obesity with diabetes. rct, n=1206, Adults with type 2 diabetes, BMI ≥27 and HbA1c 7–10%. The combination reduced weight and HbA1c in people with type 2 diabetes. (source)
- REDEFINE 1: obesity without diabetes. rct, n=3417, Adults without diabetes: BMI ≥30, or ≥27 with a weight-related condition. The combination reduced weight more than placebo; its components also had separate arms. (source)
- REDEFINE 3: cardiovascular outcomes. rct, n=7076, Age 55 Years; Adults with established cardiovascular disease and BMI ≥25, with or without diabetes. A design paper is available; cardiovascular outcome results are not yet reported. (source)
- REDEFINE 5: Japan and Taiwan. rct, n=331, Adults with high BMI and weight-related complications; 24% had type 2 diabetes. The combination reduced weight more than semaglutide in this East Asian population. (source)
- REDEFINE 6: China. rct, n=300, Age 18 Years; Obesity or Overweight. Status: completed. No clinical benefit is established by registration. (source)
- REIMAGINE 2: seven randomized arms. rct, n=2713, Adults with type 2 diabetes on metformin with or without an SGLT2 inhibitor. The higher combination dose added a small HbA1c reduction versus semaglutide. (source)
- Kidney disease and albumin leakage. rct, n=626, Age 18 Years; Chronic Kidney Disease; Type 2 Diabetes; Obesity. Status: completed. No clinical benefit is established by registration. (source)
- REDEFINE 4: versus tirzepatide. open-label, n=809, Age 18 Years; Obesity. Sponsor reported less mean weight loss with CagriSema than tirzepatide. (source)
- Food intake and stomach emptying. rct, n=62, Age 18 Years to 65 Years; Obesity. Status: completed. No clinical benefit is established by registration. (source)
- REIMAGINE 4: versus tirzepatide. open-label, n=1024, Age 18 Years; Type 2 Diabetes. Sponsor reported weight noninferiority, but not HbA1c noninferiority. (source)
- Appetite and brain imaging. rct, n=164, Age 18 Years to 65 Years; Overweight; Obesity. Conference findings on appetite and brain responses were reported; full results were not extracted. (source)
- Warfarin and atorvastatin interaction. rct, n=34, Age 18 Years to 65 Years; Obesity. Status: completed. No clinical benefit is established by registration. (source)
- REIMAGINE 3: added to basal insulin. rct, n=274, Adults with type 2 diabetes on daily basal insulin, with or without metformin. Both doses improved HbA1c when added to basal insulin. (source)
- REIMAGINE 1: early diabetes. rct, n=189, Adults with type 2 diabetes inadequately controlled by diet and exercise. Both combination doses lowered HbA1c and weight versus placebo. (source)
- REDEFINE 9: lower doses. rct, n=300, Age 18 Years; Obesity. Sponsor announced benefit at 1 mg each; full results are not published here. (source)
- Insulin sensitivity study. rct, n=158, Age 18 Years to 75 Years; Diabetes Mellitus, Type 2. Status: completed. No clinical benefit is established by registration. (source)
- Alcohol-related liver disease. rct, n=270, Age 18 Years; Alcohol-related Liver Disease. Status: completed. No clinical benefit is established by registration. (source)
- REIMAGINE 5: lower-dose comparison. rct, n=1023, Age 18 Years; Diabetes Mellitus, Type 2. Sponsor reported more weight loss with low-dose CagriSema than tirzepatide 5 mg. (source)
- Two CagriSema formulations: PK. crossover-rct, n=18, Age 18 Years to 64 Years; Obesity. Status: completed. No clinical benefit is established by registration. (source)
- REDEFINE 8: maintenance and tapering. rct, n=400, Age 18 Years; Obesity. Status: active not recruiting. No clinical benefit is established by registration. (source)
- Painful diabetic neuropathy. rct, n=142, Age 18 Years; Diabetes Mellitus, Type 2; Diabetic Peripheral Neuropathy. Status: completed. No clinical benefit is established by registration. (source)
- RAMBO: bone metabolism. rct, n=144, Age 50 Years to 70 Years; Obesity. Status: recruiting. No clinical benefit is established by registration. (source)
- REDEFINE 11: longer weight follow-up. rct, n=609, Age 18 Years; Obesity. Status: active not recruiting. No clinical benefit is established by registration. (source)
- Weight loss and metabolism. rct, n=80, Age 18 Years to 65 Years; Obesity. Status: active not recruiting. No clinical benefit is established by registration. (source)
- Youth obesity study. rct, n=460, Age 8 Years to 18 Years; Overweight; Obesity. Status: recruiting. No clinical benefit is established by registration. (source)
- REIMAGINEYOUNG: youth diabetes. rct, n=80, Age 10 Years to 18 Years; Diabetes Mellitus, Type 2. Status: recruiting. No clinical benefit is established by registration. (source)
- RASMUS: muscle health. rct, n=100, Age 50 Years to 70 Years; Obesity. Status: recruiting. No clinical benefit is established by registration. (source)
- Higher-dose CagriSema comparison. rct, n=2500, Age 18 Years; Obesity; Type 2 Diabetes. Higher semaglutide exposure is being studied; no outcome results are available. (source)
- Switching semaglutide to CagriSema. rct, n=210, Age 18 Years; Diabetes Mellitus, Type 2. Status: recruiting. No clinical benefit is established by registration. (source)
- Dual-chamber pen usability. single-arm, n=150, 85 adults with overweight/obesity and 65 with type 2 diabetes. The trial pen was usable after training; this does not validate home-mixed vials. (source)
- Meta-analysis: versus semaglutide. meta-analysis, n=3545, Three randomized trials in adults with obesity. Combination weight loss was greater; monotherapy safety needs further study. (source)
- Meta-analysis: eight trials. meta-analysis, n=6898, Eight trials in adults with excess weight or type 2 diabetes. The combination added weight loss across comparators. (source)
- Meta-analysis: five unique trials. meta-analysis, n=4746, Five trials; 4,746 unique adults, with or without diabetes. Extra weight loss was supported; pooled estimates of stomach-event risk differed. (source)
- Combination mechanism in rats. animal, Rats. The combination reduced food intake while preserving energy expenditure in rats. (source)
- Phase 2 diabetes: posted results. rct, n=92, Same phase 2 diabetes participants; counts use observed/evaluable data. Observed registry results are shown separately from the paper’s estimated treatment effects. (source)
- REIMAGINE 2: full primary sponsor table. rct, n=2713, Same REIMAGINE 2 participants; not an additional trial. The primary sponsor table reports all active and pooled placebo results. (source)
CagriSema dosage
Typical reported dose: 0.25 mg of each drug weekly to start, up to 2.4 mg of each
- Phase 2: 2.4 mg of each: 0.25 mg of each drug once weekly, then 0.5 mg of each drug once weekly, then 1 mg of each drug once weekly, then 1.7 mg of each drug once weekly once weekly, under the skin. Studied in a trial. Studied in: Adults with type 2 diabetes and BMI ≥27 on metformin, with or without an SGLT2 inhibitor. (source)
- REDEFINE 1: 2.4 mg of each: 0.25 mg of each drug once weekly, then 0.5 mg of each drug once weekly, then 1 mg of each drug once weekly, then 1.7 mg of each drug once weekly once weekly, under the skin. Studied in a trial. Studied in: Adults without diabetes: BMI ≥30, or ≥27 with a weight-related condition. (source)
- REDEFINE 2: 2.4 mg of each: 0.25 mg of each drug once weekly, then 0.5 mg of each drug once weekly, then 1 mg of each drug once weekly, then 1.7 mg of each drug once weekly once weekly, under the skin. Studied in a trial. Studied in: Adults with type 2 diabetes, BMI ≥27 and HbA1c 7–10%. (source)
- REDEFINE 5: 2.4 mg of each: 0.25 mg of each drug once weekly, then 0.5 mg of each drug once weekly, then 1 mg of each drug once weekly, then 1.7 mg of each drug once weekly once weekly, under the skin. Studied in a trial. Studied in: Adults with high BMI and weight-related complications; 24% had type 2 diabetes. (source)
- REIMAGINE 1: 2.4 mg of each: 0.25 mg of each drug once weekly, then 0.5 mg of each drug once weekly, then 1 mg of each drug once weekly, then 1.7 mg of each drug once weekly once weekly, under the skin. Studied in a trial. Studied in: Adults with type 2 diabetes inadequately controlled by diet and exercise. (source)
- REIMAGINE 3: 2.4 mg of each: 0.25 mg of each drug once weekly, then 0.5 mg of each drug once weekly, then 1 mg of each drug once weekly, then 1.7 mg of each drug once weekly once weekly, under the skin. Studied in a trial. Studied in: Adults with type 2 diabetes on daily basal insulin, with or without metformin. (source)
These are doses reported in labels, trials or user reports, not a personal plan. Check the source behind each one.
CagriSema side effects and risks
Reported side effects
- Stomach and bowel symptoms: 79.6% versus 39.9% placebo in REDEFINE 1; 72.5% versus 34.4% in REDEFINE 2., moderate (source)
- Nausea: REIMAGINE 3: 31.1% at 2.4 mg each, 26.9% at 1 mg each, 3.3% placebo., moderate (source)
- Diarrhea: REIMAGINE 3: 15.6%, 10.8% and 3.3%, respectively., moderate (source)
- Vomiting: REIMAGINE 3: 14.4%, 9.7% and 1.1%, respectively., moderate (source)
- Constipation: REIMAGINE 3: 11.1%, 11.8% and 5.5%, respectively., moderate (source)
- Injection-site reactions: 12.2% versus 3.0% placebo in REDEFINE 1., mild (source)
- Gallbladder disorders: 4.1% versus 1.0% placebo in REDEFINE 1., serious (source)
- Pancreatitis: 0.2% versus 0% placebo in REDEFINE 1; 0.3% versus 0% in REDEFINE 2., serious (source)
- Clinically significant low blood sugar: REDEFINE 2: level 2 events 6.0% versus 3.3% placebo., serious (source)
- Severe low blood sugar: REDEFINE 2: 0.2% versus 0%; both affected patients used sulfonylureas., serious (source)
- Dehydration-related kidney injury: Semaglutide component warning; no reliable combination specific rate., serious (source)
- Severe allergic reaction: Semaglutide component postmarketing reports; combination specific rate unknown., serious (source)
Stop and get help if
- Severe persistent belly pain, with or without vomiting: Stop and get urgent assessment for pancreatitis or gallbladder disease.
- Swelling of face or throat, breathing trouble or collapse: Stop and call emergency services.
- Confusion, seizure, unconsciousness or persistent low sugar: Call emergency services; do not give food or drink if unconscious.
- Repeated vomiting, very little urine or severe dizziness: Get urgent assessment for dehydration and kidney injury.
- Sudden vision loss or a new major vision change: Get emergency care for sudden loss of sight; urgent assessment for other new changes.
- Persistent squeezing chest pain, or chest pain with breathlessness: Get emergency assessment.
Who should avoid it
- pregnant: Weight-loss use is unsuitable in pregnancy; semaglutide may harm the fetus.
- breastfeeding: The combination lacks infant safety data; breastfeeding was excluded from trials.
- tryingToConceive: Semaglutide labeling calls for stopping at least 2 months before planned pregnancy.
- under18: Combination dosing in youth is still under study; adult results do not establish safety.
- mtcOrMen2: Semaglutide's label blocks use with personal/family MTC or MEN2. Its boxed warning reports thyroid C-cell tumors in rodents; human relevance is unknown, and CagriSema has no approved label.
- eatingDisorderHistory: Precaution: strong appetite suppression can worsen restrictive eating or poor nutrition.
- gastroparesis: Semaglutide is not recommended with severe gastroparesis.
- pancreatitisHistory: Review prior pancreatitis; cases occurred in combination trials.
- gallbladderDisease: Gallbladder events were more frequent than placebo in REDEFINE trials.
- diabeticRetinopathy: Rapid glucose improvement may worsen existing retinopathy; arrange eye monitoring.
- diabetes: Insulin or sulfonylureas may need clinician adjustment to avoid low blood sugar.
- kidneyDisease: Vomiting or diarrhea can cause dehydration and kidney injury; check kidney function if symptoms persist.
- liverDisease: Component PK data do not establish long-term combination safety in severe liver disease.
- heartCondition: Monitor heart rate and symptoms; combination cardiovascular outcomes are still pending.
- surgeryPlanned: Tell the anesthesia team; delayed stomach emptying can increase aspiration risk.
- testedAthlete: Cagrilintide remains unapproved, so S0 applies; semaglutide monitoring is a separate issue.
- other: Prior serious allergy to semaglutide, cagrilintide or formulation ingredients should stop use.
Interactions
- Insulin and sulfonylureas: Low-sugar risk can rise. Both severe cases in REDEFINE 2 used sulfonylureas; clinician-led dose review matters.
- Extra GLP-1 or amylin drugs: CagriSema already contains semaglutide and cagrilintide. Added GLP-1 or amylin exposure has no established safe schedule.
- Warfarin and other monitored oral drugs: Review INR or drug response during changes. The dedicated warfarin/atorvastatin study is complete but results were not located.
- Oral contraception: Combination absorption data are incomplete. Vomiting or diarrhea can undermine pill use; review backup needs with a clinician.
Product quality risks
- A community “CagriSema” blend is not the controlled dual-chamber trial product.
- Online semaglutide samples had 7.7–14.37% purity, 28.56–38.69% excess content and detectable endotoxin. This was not a CagriSema test.
- Wrong component ratio, vial/unit confusion and contamination can cause harm.
- FDA warns of counterfeit semaglutide products and dosing errors with unapproved injections.
How CagriSema works
Cagrilintide signals fullness through amylin pathways. Semaglutide activates GLP-1 receptors, supporting fullness and glucose-dependent insulin release. The two drugs act through complementary pathways; their combination can reduce eating more than either drug alone.
- Amylin and calcitonin-family receptors: Cagrilintide adds fullness signals through brain pathways.
- GLP-1 receptor: Semaglutide supports fullness, insulin release when glucose is high, and slower stomach emptying.
Half-life: Cagrilintide 159–195 hours; semaglutide 145–165 hours in the phase 1b study.
Gaps: No approved combination label or independently verified clinician-published dosing protocol was found. REDEFINE 4/9 and REIMAGINE 5 results remain sponsor-reported here, with incomplete safety tables. Cardiovascular outcomes, long-term maintenance and rare harms remain unsettled. No verified human trials support adding tirzepatide, retatrutide or extra GLP-1 drugs. No validated home-blend reconstitution, pH adjustment, storage or shelf life was found. Combination dose numbers are per component; a total blend dose can hide two different exposures. No population-use prevalence or reliable adverse-event incidence can be inferred from forum posts. No cagrilintide-specific 503A category or PCAC decision could be confirmed. REIMAGINE 4 outcomes are available only in a sponsor filing here; full safety tables remain missing. The exact text of the REIMAGINE 2 correction was unavailable; the current peer-reviewed supplement was retrieved.
Related to CagriSema
- Cagrilintide: An unapproved weekly amylin analogue with weight-loss trials and common stomach symptoms.
- Pramlintide: A diabetes medicine that copies a hormone released with insulin; Symlin products are discontinued.
- Semaglutide: A GLP-1 medicine with strong weight, glucose, heart and kidney evidence; dose and formulation matter.
- Tirzepatide: A weekly GIP/GLP-1 injection with strong diabetes and weight-loss evidence and common stomach side effects.
Sources
- 503B Bulk Drug Substances List, FDA · FDA · 2026
- The Prohibited List, World Anti-Doping Agency · World Anti-Doping Agency · 2026
- Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society., Mozaffarian D et al. · The American journal of clinical nutrition · 2025
- Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act
- Chest pain, NHS
- European Medicines Agency decision P/0307/2023 of 4 August 2023 on the granting of a product specific waiver for cagrilintide / semaglutide (EMEA-003059-PIP02-23)
- FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight Loss, US Food and Drug Administration
- PIP Search Page, MHRA
- Therapeutic Goods (Poisons Standard—October 2026) Instrument 2026
- Understanding your responsibilities when importing, compounding and supplying unapproved peptide products
- Vision loss, NHS
- Wegovy PI, Novo Nordisk
- Cagrilintide-semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study., Rosenstock J et al. · Lancet (London, England) · 2026
- Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study., Buse JB et al. · The lancet. Diabetes & endocrinology · 2026
- CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1., Verma S et al. · Hypertension (Dallas, Tex. : 1979) · 2026
Sources checked: 2026-10-18.
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