Cagrisema: A Cagrilintide-Plus-Semaglutide Combination for Obesity

This content is provided by Superpower Health for educational and informational purposes only. Cagrisema is an investigational combination therapy that is not FDA-approved as of April 2026. It is not available through Superpower or by prescription; access outside of enrolled clinical trials is not currently authorized. This page is not a substitute for medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider.

Obesity prevalence among U.S. adults reached 40.3% between August 2021 and August 2023, according to a 2024 NCHS Data Brief by Emmerich and colleagues, defining the scale of the population for whom effective pharmacotherapy is now a clinical question rather than a theoretical one. The first generation of GLP-1 receptor agonists changed what was thought possible in obesity pharmacology. The second question (whether activating a complementary pathway could push weight loss further) is now being answered by Phase 3 data. The answer, from Novo Nordisk's REDEFINE program, is a qualified yes: combining cagrilintide, a long-acting amylin analog, with semaglutide 2.4 mg produces greater weight loss than semaglutide alone. Whether that advantage is large enough to matter clinically, and how it compares to what tirzepatide and retatrutide achieve, is the more interesting question.

This article covers how cagrisema works, what the REDEFINE Phase 3 trials found, how the efficacy and safety data compare to available alternatives, and which biomarkers are relevant to anyone evaluating their metabolic health in this therapeutic landscape.

Key Takeaways

• Regulatory Status: As of April 2026, cagrisema is not FDA-approved. Novo Nordisk submitted a regulatory filing in 2025; approval is anticipated in 2026 per company guidance. Cagrisema is not available outside of clinical trials in the United States.
• Research Stage: Phase 3 complete. REDEFINE-1 (obesity without T2D) and REDEFINE-2 (obesity with T2D) published in New England Journal of Medicine in 2025. REDEFINE-3 (cardiovascular outcomes) is ongoing; CV-endpoint data are not yet available.
• Availability: Not available through Superpower or by prescription in the United States as of April 2026. For clinical trial enrollment information, see clinicaltrials.gov.
• Prescribing information: PubChem CID 155142498 (cagrilintide component)
• How it works: Combines amylin receptor agonism (cagrilintide) and GLP-1 receptor agonism (semaglutide) to target two complementary satiety pathways simultaneously.
• What the research shows: In REDEFINE-1, coadministered cagrilintide 2.4 mg and semaglutide 2.4 mg produced a mean body weight reduction of 20.4% at 68 weeks versus 3.0% with placebo in adults with overweight or obesity without type 2 diabetes. REDEFINE-2 showed 13.7% weight loss at 68 weeks in a type 2 diabetes population.

Where Cagrisema Comes From and How It Works

Origin and development rationale

Cagrisema is not a single compound. It is the once-weekly subcutaneous co-administration of cagrilintide 2.4 mg (a long-acting amylin analog) and semaglutide 2.4 mg (a well-characterized GLP-1 receptor agonist) as a fixed-dose combination. Novo Nordisk developed this pairing based on a specific mechanistic hypothesis: that amylin and GLP-1 receptor agonism engage overlapping but distinct satiety circuits, and that stimulating both simultaneously would produce additive weight loss exceeding what either compound achieves alone. The development pathway moved from a Phase 1b tolerability study published in The Lancet in 2021 by Enebo and colleagues, which confirmed acceptable safety and pharmacokinetics when the two compounds were coadministered, through Phase 2, and into a Phase 3 program registered under the name REDEFINE.

Amylin receptor agonism: how cagrilintide works

Amylin is a 37-amino-acid peptide co-secreted alongside insulin from pancreatic beta cells in response to meals. Its primary physiological roles include inducing satiation, slowing gastric emptying, and suppressing glucagon. As a 2025 review by Walker, Aitken, and colleagues published in Nature Reviews Endocrinology established, amylin acts centrally through the area postrema and hypothalamus, reducing food intake through circuits that are anatomically and mechanistically distinct from those activated by GLP-1. A 2022 paper by Boyle, Zheng, and Lutz in Journal of Clinical Medicine clarified the mediators of amylin action in metabolic control, particularly its interaction with calcitonin receptor/receptor activity-modifying protein (CTR/RAMP) complexes in the brainstem and hypothalamus. A 2025 review by Lutz in Neuropharmacology further characterized amylin's role in inducing satiation and reducing meal-related food reward, including its specific effects on high-fat consumption. A foundational 2017 review by Boyle and colleagues in Molecular Metabolism set out amylin's role in both homeostatic and hedonic control of eating, providing the mechanistic rationale for pursuing amylin analogs in obesity. Amylin-based weight management therapy also has a longer clinical pedigree than cagrilintide alone suggests: a 12-month RCT by Smith and colleagues in Diabetes Care in 2008 demonstrated that pramlintide, the earlier generation amylin analog, produced sustained weight loss in non-diabetic obese adults, establishing the first durable human evidence that amylin agonism can produce meaningful weight loss. In people with obesity, endogenous amylin signaling is blunted; cagrilintide restores pharmacological activation of this pathway at a concentration and duration achievable with once-weekly dosing. The dose-finding Phase 2 work, a multicentre randomized trial of 706 adults without diabetes (BMI of at least 30, or at least 27 with hypertension or dyslipidaemia) published in The Lancet in 2021 by Lau and colleagues, established that once-weekly cagrilintide produced dose-dependent mean weight reductions ranging from approximately 6.0% at lower doses up to 10.8% at 4.5 mg at 26 weeks, versus 3.0% with placebo, confirming that amylin agonism alone drives meaningful weight loss and informing the selection of 2.4 mg for the combination program.

GLP-1 receptor agonism: the semaglutide component

The semaglutide component of cagrisema is semaglutide 2.4 mg, the same dose used in the approved weekly formulation for weight management. GLP-1 receptor agonists act through vagal afferents, the hypothalamus, and brainstem circuits to suppress appetite, slow gastric emptying, and reduce food intake. As a standalone agent at 2.4 mg weekly, semaglutide produced approximately 15.2% body weight loss at 104 weeks in the STEP 5 trial, reported by Garvey and colleagues in Nature Medicine in 2022, in a randomized controlled trial of 304 adults with overweight or obesity. The semaglutide 2.4 mg cardiovascular outcomes data come from the SELECT trial, reported by Lincoff and colleagues in the New England Journal of Medicine in 2023, a double-blind RCT of 17,604 adults aged 45 or older with preexisting cardiovascular disease and BMI of 27 or higher without diabetes, randomized to once-weekly subcutaneous semaglutide 2.4 mg or placebo over a mean follow-up of 39.8 months, which reported a 20% reduction in the primary composite MACE endpoint (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) in the semaglutide group versus placebo (HR 0.80, 95% CI 0.72 to 0.90; p < 0.001). That result applies to this specific at-risk CVD population and should not be extrapolated to cagrisema itself. Because REDEFINE-3 is still enrolling, those SELECT results establish the GLP-1 component's cardiovascular evidence base only and should not be interpreted as evidence that cagrisema itself reduces cardiovascular events.

Why combining both mechanisms may exceed either alone

The mechanistic rationale is complementarity rather than redundancy. GLP-1 acts primarily through vagal and hypothalamic circuits. Amylin acts through the area postrema, a circumventricular region outside the blood-brain barrier, engaging appetite circuits that GLP-1 does not directly target. Stimulating both pathways simultaneously may produce additive satiety signaling without proportionally increasing the dose-dependent side effects associated with either mechanism. The hypothesis was tested in a Phase 2 RCT by Frias and colleagues published in The Lancet in 2023, which enrolled 92 adults with type 2 diabetes and overweight or obesity and found that cagrisema produced 15.6% body weight loss at 32 weeks versus 5.1% with semaglutide alone and 8.1% with cagrilintide alone, confirming that co-administration exceeded either component in that population at that timepoint. The Phase 3 REDEFINE program was designed to test this advantage at scale.

What the Phase 3 REDEFINE Trials Found

REDEFINE-1: obesity without type 2 diabetes

REDEFINE-1 is the primary Phase 3 efficacy trial for cagrisema in adults with overweight or obesity who do not have type 2 diabetes. Results were published by Garvey, Blüher, and the REDEFINE 1 Study Group in New England Journal of Medicine in 2025. The trial enrolled adults with a BMI of 30 or higher (or 27 or higher with at least one weight-related comorbidity) and randomized them to once-weekly subcutaneous coadministered cagrilintide 2.4 mg and semaglutide 2.4 mg or placebo for 68 weeks. The mean body weight change from baseline to week 68 was -20.4% with cagrisema versus -3.0% with placebo, a difference of 17.3 percentage points (95% CI: -18.1 to -16.6; P < 0.001). Participants receiving cagrisema were significantly more likely than placebo recipients to achieve weight-loss targets of 5% or more, 20% or more, 25% or more, and 30% or more. A secondary analysis of REDEFINE-1 cardiovascular data, published in Hypertension in 2026 by Verma and colleagues, found that cagrisema reduced mean systolic blood pressure by 10.9 mm Hg versus 2.8 mm Hg with placebo, with 63.0% of the cagrisema group versus 32.0% of the placebo group reaching blood pressure targets at week 68.

The initial topline result disclosed by Novo Nordisk via corporate communication on December 20, 2024 cited a 22.7% weight loss figure. Market commentary described this as "below expectation" relative to Novo's prior guidance of approximately 25%. The peer-reviewed publication in New England Journal of Medicine by Garvey and colleagues is the authoritative source; the published primary endpoint is -20.4% mean body weight change. Individual results varied, and the published peer-reviewed figure should be used for clinical context. A 20.4% mean weight reduction remains a clinically substantial result.

REDEFINE-2: obesity with type 2 diabetes

REDEFINE-2 is the companion Phase 3 trial in adults with overweight or obesity and type 2 diabetes. Results were published simultaneously by Davies, Bajaj, and the REDEFINE 2 Study Group in New England Journal of Medicine in 2025. The trial enrolled 1,206 adults with T2D across 12 countries and randomized participants to cagrisema or placebo for 68 weeks. Mean body weight decreased by 13.7% in the cagrisema group versus 3.4% with placebo. For glycemic control, 73.5% of cagrisema-treated participants achieved HbA1c targets of 6.5% or lower, compared to 15.9% with placebo. Gastrointestinal adverse events occurred in 72.5% of cagrisema-treated participants and were described as transient and predominantly mild or moderate in severity. These dual benefits (meaningful weight reduction alongside glycemic improvement) are consistent with what the Phase 2 Frias 2023 data had suggested.

REDEFINE-3: cardiovascular outcomes (ongoing)

REDEFINE-3 is the dedicated cardiovascular outcomes trial for cagrisema and is still ongoing as of April 2026. No peer-reviewed cardiovascular endpoint data for cagrisema itself have been published. Articles and commentary attributing cardiovascular benefits to cagrisema directly are extrapolating from the GLP-1 component's SELECT-trial evidence base, not from cagrisema-specific CV data. The REDEFINE-3 results will be required before cagrisema's effect on major adverse cardiovascular events can be stated with confidence.

Regulatory and Legal Status

FDA submission and anticipated timeline

As of April 2026, cagrisema is not FDA-approved for any indication. Novo Nordisk submitted a regulatory filing to the FDA in 2025; the company has indicated that approval is anticipated in 2026 per public guidance. Because the regulatory process is ongoing, no approval date can be confirmed. Cagrisema is not available as a prescription medication in the United States and is not available through compounding pharmacies. There is currently no legal pathway to obtain cagrisema outside of an enrolled, registered clinical trial. Cagrisema is listed for ongoing study at clinicaltrials.gov.

What would need to change for availability

For cagrisema to become available by prescription in the United States, the FDA would need to complete its review of Novo Nordisk's NDA and issue an approval. If approved, it would become available as a prescription obesity medication dispensed through a licensed prescriber. Unlike compounds that face Category 2 compounding restrictions, cagrisema's path to availability is straightforwardly tied to the outcome of the NDA review. If the FDA approves the filing, a licensed provider could prescribe it; if additional data are requested via a Complete Response Letter, availability would be delayed pending that supplemental submission. The timeline remains under active regulatory review as of April 2026.

What this means practically

Products sold online under the name cagrisema, cagrilintide-semaglutide, or related terms through research compound vendors are not FDA-regulated, have no verified manufacturing standards, and carry unknown contamination, dosing, and safety risks. The cagrilintide component of cagrisema is a distinct proprietary peptide; products sold under its name without pharmaceutical oversight are not verified to contain the compound in any meaningful or safe form. The only reliable access pathway as of April 2026 is enrollment in an active clinical trial or, if and when FDA approval occurs, evaluation by a licensed prescriber.

Cagrisema in Context: Comparisons and Competitive Landscape

Placing cagrisema's efficacy data in clinical context requires attention to the specific trials being compared. Cross-trial comparisons are unreliable due to differences in study design, patient populations, treatment duration, and endpoints. The following comparisons are for scientific context only. These compounds have fundamentally different regulatory statuses, evidence bases, and risk profiles. A 2025 systematic review of emerging obesity pharmacotherapies by Kokkorakis and colleagues in Pharmacological Reviews situates cagrisema alongside retatrutide and the broader set of next-generation agents currently under development, providing single-source context for how these compounds map onto the existing regulatory and clinical landscape.

Versus tirzepatide (dual GIP/GLP-1 agonist)

Tirzepatide is the most directly relevant approved comparator for cagrisema. SURMOUNT-1, published in New England Journal of Medicine in 2022 by Jastreboff and colleagues, enrolled 2,539 adults with obesity without T2D and found that tirzepatide 15 mg produced a mean weight loss of 20.9% at 72 weeks. By this cross-trial comparison, cagrisema's REDEFINE-1 result of 20.4% at 68 weeks falls within a similar range, though the trials used different populations, durations, and dose-escalation designs that make direct numerical comparison uninformative. SURMOUNT-5, published in New England Journal of Medicine in 2025 by Aronne and colleagues, was a head-to-head randomized trial comparing tirzepatide to semaglutide 2.4 mg in 751 adults with obesity, finding that tirzepatide produced -20.2% weight loss versus -13.7% for semaglutide 2.4 mg at 72 weeks. The SURMOUNT-5 result confirms tirzepatide's advantage over semaglutide alone, providing context for why adding the cagrilintide amylin component to semaglutide was pursued. No head-to-head trial between cagrisema and tirzepatide has been published.

Versus retatrutide (triple GIP/GLP-1/glucagon agonist)

Retatrutide is a triple GIP, GLP-1, and glucagon receptor agonist in Phase 3 development. Phase 2 data published in New England Journal of Medicine in 2023 by Jastreboff, Kaplan, Frías, and colleagues showed that retatrutide 12 mg produced a mean weight loss of 24.2% at 48 weeks in 338 adults with obesity, without the benefit of a full 68-week trial duration. A separate Phase 2 trial in type 2 diabetes by Rosenstock and colleagues in The Lancet in 2023 reported up to a 2.02 percentage-point HbA1c reduction and approximately 16.9% weight loss at 36 weeks, providing glycemic comparator context. Retatrutide's Phase 2 ceiling appears higher than cagrisema's REDEFINE-1 Phase 3 result; whether that advantage persists in Phase 3, and whether it is accompanied by a different safety profile, will not be known until Phase 3 data are published. These compounds are not equivalent and should not be treated as interchangeable. Both are investigational as of April 2026.

Versus semaglutide monotherapy

The incremental value of adding cagrilintide to semaglutide is the central question for cagrisema's clinical positioning. Semaglutide 2.4 mg monotherapy produced approximately 15.2% weight loss at 104 weeks in STEP 5. The cagrisema REDEFINE-1 result of 20.4% at 68 weeks represents a meaningful absolute difference above semaglutide alone. The Phase 2 Frias data showed cagrisema produced 15.6% at 32 weeks in a T2D population versus 5.1% for semaglutide alone at 32 weeks, again suggesting an additive effect. The magnitude of clinical benefit from adding the amylin component is real but moderate relative to what was anticipated from pre-trial expectations. A 2024 systematic review and meta-analysis by Dutta, Nagendra, and colleagues published in Indian Journal of Endocrinology and Metabolism synthesized available RCT data and confirmed that cagrisema outperforms semaglutide monotherapy on weight loss outcomes across available studies.

Clinical guideline context

Current obesity pharmacotherapy guidelines pre-date the published REDEFINE data but establish how combination GLP-1-based therapies will likely be evaluated once approved. The 2022 American Gastroenterological Association clinical practice guideline by Grunvald and colleagues in Gastroenterology issued a strong conditional recommendation for GLP-1 receptor agonist pharmacotherapy in combination with lifestyle intervention for adults with obesity. A 2023 JAMA clinical review by Elmaleh-Sachs and colleagues positioned GLP-1 receptor agonists within the broader obesity treatment algorithm alongside lifestyle, pharmacologic, and surgical options. More recently, a 2025 Canadian clinical practice guideline update by Pedersen and colleagues in CMAJ incorporated semaglutide, tirzepatide, and emerging combination agents into its recommended framework for adult obesity management. These guidelines are the context into which cagrisema, if approved, would be introduced.

Safety: What Is and Is Not Known

Gastrointestinal adverse events

The predominant adverse effect profile of cagrisema is gastrointestinal. In REDEFINE-1, approximately 80% of cagrisema-treated participants experienced GI adverse events, described as mainly transient and mild to moderate in severity, including nausea, vomiting, and diarrhea. In REDEFINE-2, GI events occurred in 72.5% of the cagrisema group. These rates are consistent with the known pharmacology of GLP-1 receptor agonists and are comparable to what has been reported with tirzepatide in SURMOUNT-1. A 2025 network meta-analysis by Ismaiel and colleagues in the International Journal of Obesity quantified nausea, vomiting, diarrhea, and constipation rates across GLP-1 receptor agonists in non-diabetic overweight or obese adults, providing class-level benchmarks against which cagrisema's GI tolerability profile can be situated. A 2026 state-of-the-art review by Kunutsor and Seidu in Drugs documented that GLP-1 receptor agonist class adverse events include cholelithiasis, gastroparesis, and rare pancreatitis signals in addition to the predominant GI effects; these class signals are relevant to the GLP-1 component of cagrisema. The specific safety profile of the amylin component in combination was assessed in the thorough QT study of cagrilintide published in Diabetes, Obesity and Metabolism in 2024 by Gabe and colleagues, which found no clinically relevant QTc prolongation at doses up to 4.5 mg in 105 healthy participants.

Lean mass considerations

A relevant safety question for any compound producing 20% total body weight loss is the proportion of that loss attributable to lean mass rather than fat. A 2024 review by Neeland, Linge, and Birkenfeld in Diabetes, Obesity and Metabolism documented that lean mass reductions with GLP-1-based therapies range from approximately 15% to 60% of total weight lost, depending on population, drug-specific effects, and comorbidities. The authors characterized many of these changes as adaptive rather than pathological, noting that reductions in muscle volume appear commensurate with what would be expected given the degree of weight loss. At 20.4% total weight loss, lean mass preservation is a meaningful clinical consideration. Monitoring body composition, protein intake, and resistance exercise capacity are strategies discussed in the literature for mitigating lean mass loss during weight-loss pharmacotherapy.

Weight regain after discontinuation

The STEP 1 extension study, published in Diabetes, Obesity and Metabolism in 2022 by Wilding, Batterham, and colleagues, followed 327 participants from the parent STEP 1 trial for one year after treatment discontinuation and found that participants regained two-thirds of their prior weight loss — mean weight change from randomization went from -17.3% at week 68 to -5.6% at week 120 in the semaglutide group versus -2.0% to +0.1% in the placebo group, with cardiometabolic improvements in waist circumference, systolic blood pressure, HbA1c, and lipids largely reverting toward baseline. Because the GLP-1 component of cagrisema is the same molecule and dose, similar weight regain dynamics should be expected after discontinuation. No cagrisema-specific discontinuation data have been published, but the class behavior is well characterized for the semaglutide component. This context matters for any long-term evaluation of the drug's clinical benefit.

Who Should Not Use Cagrisema

Cagrisema is investigational and not yet FDA-approved. The following populations face elevated theoretical or mechanistic risk based on available data from the REDEFINE trials and the known safety profiles of its components. A licensed provider will conduct a full clinical evaluation before determining eligibility if and when cagrisema becomes available by prescription.

• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2): GLP-1 receptor agonists carry a class boxed warning for this population; the semaglutide component makes this contraindication directly applicable.
• History of pancreatitis: GLP-1 receptor agonism has been associated with elevated pancreatitis risk in post-marketing surveillance; the semaglutide component carries this class signal.
• Diabetic or severe gastroparesis: GLP-1 receptor agonism further slows gastric emptying; this interaction may worsen gastroparesis in susceptible individuals.
• Severe renal impairment: Pharmacokinetic data for the amylin and GLP-1 components in severe renal disease require individual assessment.
• Pregnancy and breastfeeding: No safety data exist for either component in pregnancy; semaglutide carries a recommendation to discontinue prior to conception based on animal reproductive toxicity data.
• Active or prior cholelithiasis: GLP-1 receptor agonists are associated with increased gallstone formation; the semaglutide component makes this clinically relevant.
• Severe hepatic impairment: Pharmacokinetics have not been fully characterized at extreme hepatic impairment levels for the combination.
• Known hypersensitivity to semaglutide, cagrilintide, or any excipient.

Which Biomarkers Are Relevant if You Are Exploring Weight Management?

The metabolic systems that cagrisema acts on are the same systems that objective biomarker testing characterizes. Understanding your current values provides a baseline for evaluating any pharmacological or lifestyle intervention, independent of which specific compound eventually becomes accessible.

• HbA1c: The three-month average of blood glucose and the primary glycemic endpoint in REDEFINE-2. Hemoglobin A1c places current glycemic status in the context of pre-diabetes, type 2 diabetes, or normal glucose regulation, all of which affect pharmacotherapy candidacy for this drug class.
• Fasting glucose and fasting insulin: Together, these characterize insulin sensitivity before overt HbA1c elevation occurs. Fasting insulin alongside glucose identifies insulin resistance, the metabolic substrate for most obesity-related cardiovascular risk, and reflects the physiological systems that GLP-1 and amylin signaling modulate.
• High-sensitivity C-reactive protein (hs-CRP): Obesity is characterized by low-grade systemic inflammation, and GLP-1 receptor agonists have demonstrated anti-inflammatory effects in clinical trials beyond weight reduction. Measuring hs-CRP provides a baseline for assessing inflammatory burden and tracking metabolic improvements.
• Lipid panel (triglycerides, HDL, LDL, ApoB): Weight-loss pharmacotherapy consistently produces improvements in triglycerides and HDL. A baseline lipid panel establishes the cardiometabolic context and provides a reference point for tracking change. The REDEFINE-1 cardiovascular analysis confirmed improvements in cardiovascular parameters beyond weight, making baseline lipid context especially relevant.
• Body composition: BMI and waist circumference are the standard entry criteria in REDEFINE trials. For individuals evaluating the lean mass question, body composition biomarkers including DEXA-derived fat and lean mass measurements provide clinical detail that weight alone does not capture, particularly given the 15-60% lean mass loss range documented for GLP-1-based therapies.
• Blood pressure: The REDEFINE-1 cardiovascular analysis documented clinically meaningful systolic blood pressure reductions with cagrisema. Establishing a blood pressure baseline contextualizes any cardiometabolic benefits observed if this compound becomes available.
• Kidney function (creatinine, eGFR) and liver enzymes: GLP-1 receptor agonists require organ function monitoring at baseline and during therapy. Creatinine and estimated GFR establish renal safety context; liver enzyme assessment through a comprehensive metabolic panel is standard pre-treatment safety evaluation for this drug class.

The Bottom Line

Cagrisema's REDEFINE Phase 3 results position it as a meaningful advance in weight management research pending regulatory review. A 20.4% mean weight reduction at 68 weeks in REDEFINE-1 exceeds what semaglutide monotherapy achieves and sits within the same range as tirzepatide's Phase 3 data. The press-release narrative framing the result as "disappointing" relative to a 25% pre-trial expectation obscures the clinical reality: 20.4% mean weight reduction is substantially above the semaglutide-alone ceiling and above what any pharmacotherapy achieved prior to the GLP-1 era. The question of whether the incremental benefit over tirzepatide, which acts through a different mechanism, justifies a place in the treatment algorithm will be answered by how providers and payers evaluate the comparative data once the compound is approved.

Regardless of when approval arrives, the metabolic biomarkers that define candidacy and treatment response are measurable now. Understanding where your HbA1c, fasting insulin, lipid panel, and body composition stand is a necessary step before any provider can evaluate whether cagrisema, tirzepatide, semaglutide, or another approach is clinically appropriate for your situation. That principle, objective data before clinical decisions, is what Superpower is built around: the conviction, reflected in our approach to preventive health, that knowing your biology is the foundation for every decision that follows.

IMPORTANT SAFETY INFORMATION

Cagrisema (coadministered cagrilintide 2.4 mg and semaglutide 2.4 mg) is an investigational combination therapy that is not FDA-approved for any indication as of April 2026. Novo Nordisk submitted a regulatory filing in 2025; no approval has been issued. Cagrisema is not a Category 2 bulk drug substance under FDA Section 503A and has not been reviewed for compounding eligibility; neither the cagrilintide nor the cagrisema combination is eligible for compounding under 503A or 503B pathways. The semaglutide component has been subject to ongoing FDA enforcement activity related to drug shortage status and compounded formulations, but that regulatory context does not authorize compounding of the cagrisema combination. Cagrisema is not available by prescription in the United States and is not available through any compounding pharmacy. Superpower is a technology platform; Superpower does not prescribe, sell, compound, or facilitate access to cagrisema.

Research stage: Phase 3 complete (REDEFINE-1 and REDEFINE-2 published in New England Journal of Medicine, 2025). REDEFINE-3 (cardiovascular outcomes) is ongoing; no CV endpoint data for cagrisema itself have been published as of April 2026. Long-term safety data beyond 68 weeks in large populations has not been published.

Boxed warning (semaglutide component, extrapolated from approved semaglutide labeling): In rodent studies, semaglutide caused dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. Cagrisema is contraindicated in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Patients should be counseled regarding the potential risk of MTC and symptoms of thyroid tumors.

Contraindications (based on semaglutide component labeling and REDEFINE trial exclusion criteria): personal or family history of medullary thyroid carcinoma or MEN2; history of pancreatitis; severe gastroparesis; severe renal impairment (pharmacokinetics not fully characterized); pregnancy and breastfeeding (no safety data); known hypersensitivity to semaglutide, cagrilintide, or any excipient.

Warnings: gastrointestinal adverse events (nausea, vomiting, diarrhea, constipation; occurring in approximately 72-80% of participants in REDEFINE trials, predominantly mild to moderate and transient); cholelithiasis and cholecystitis (class-level GLP-1 RA signal); lean mass reduction as a proportion of total weight lost (class-level, mitigated by resistance training and protein intake); weight regain following discontinuation (expected based on semaglutide class data); QTc prolongation: cagrilintide was not associated with clinically relevant QTc prolongation in a dedicated thorough QT study by Gabe and colleagues published in Diabetes, Obesity and Metabolism in 2024.

Products sold online under the name cagrisema or cagrilintide-semaglutide through research compound vendors are not FDA-regulated, have no verified manufacturing standards, and carry unknown contamination, dosing, and safety risks. There is no legal pathway to obtain pharmaceutical-grade cagrisema for human use outside of an enrolled, IRB-approved clinical trial as of April 2026.

For clinical trial enrollment information: clinicaltrials.gov. For information about Superpower's services: superpower.com/how-it-works.

Additional Questions

What are the main side effects of cagrisema?

In REDEFINE-1 and REDEFINE-2, gastrointestinal adverse events were the most common, occurring in approximately 72-80% of participants. These included nausea, vomiting, diarrhea, and constipation; most were described as transient and mild to moderate in severity, occurring primarily during dose escalation. Additional class-level concerns with the semaglutide component include cholelithiasis, rare pancreatitis, and (based on animal data) a class warning for medullary thyroid carcinoma in individuals with a relevant history. The amylin component (cagrilintide) was confirmed to have no clinically relevant QTc prolongation in a dedicated thorough QT study in 2024.

Does cagrisema cause lean mass loss?

No compound-specific DEXA-based lean mass data from REDEFINE have been published as of April 2026. Based on published data for GLP-1-based therapies generally, a 2024 review by Neeland, Linge, and Birkenfeld documented that lean mass reductions range from approximately 15% to 60% of total weight lost, depending on the population and compound. These changes were characterized as largely adaptive given the degree of weight loss rather than as pathological muscle wasting. Resistance training and adequate protein intake are commonly recommended strategies for lean mass preservation during weight-loss pharmacotherapy in this class.

What biomarkers should I check before starting any obesity pharmacotherapy?

The standard pre-treatment metabolic assessment includes fasting glucose, HbA1c, fasting insulin, a lipid panel (including triglycerides, HDL, LDL, and ApoB), hs-CRP, blood pressure, and a comprehensive metabolic panel for kidney and liver function. These are the same markers used as primary and secondary endpoints in the REDEFINE trials and in SURMOUNT. See the biomarkers for metabolic health and weight management for additional context on what these values indicate and how they are used to evaluate candidacy.