What is Cagrilintide?
Cagrilintide is a long-acting acylated amylin analogue designed for once-weekly dosing. It is being developed by Novo Nordisk both as a standalone treatment and in combination with semaglutide (CagriSema). In Phase 3 trials in people without diabetes, the combination produced average weight loss of about 20% to 23%, depending on whether people who stopped treatment are counted. In the head-to-head REDEFINE 4 trial, however, it failed to show non-inferiority to tirzepatide 15 mg (20.2% vs 23.6% at 84 weeks).
What Cagrilintide Is Investigated For
Cagrilintide is a long-acting amylin analogue investigated for weight management, developed by Novo Nordisk mainly as the combination partner for semaglutide in CagriSema, and since late 2025 also as a standalone therapy in Phase 3. The strongest evidence comes from the Phase 3 REDEFINE program. In REDEFINE 1 (obesity without diabetes), CagriSema produced 20.4% mean weight loss at 68 weeks counting everyone randomized (22.7% if taken as intended), versus 14.9% (16.1%) with semaglutide alone, 11.5% (11.8%) with cagrilintide alone and 3.0% (2.3%) with placebo. REDEFINE 2 (obesity with type 2 diabetes) showed 13.7% versus 3.4% with placebo. In the open-label REDEFINE 4 trial, CagriSema missed its non-inferiority goal against tirzepatide 15 mg. Alone, cagrilintide produced 6.0% to 10.8% weight loss across doses of 0.3 to 4.5 mg over 26 weeks in Phase 2 (placebo 3.0%), and 11.8% at 68 weeks in the cagrilintide-only arm of REDEFINE 1. Neither is FDA-approved as of October 2026. Novo Nordisk submitted CagriSema 2.4 mg/2.4 mg to the FDA in December 2025, and a decision is expected in Q4 2026. Cagrilintide alone entered a dedicated Phase 3 program (RENEW) in November 2025. The main honest caveats: its cardiovascular outcomes trial (REDEFINE 3) has not yet reported; GI side effects are very common (79.6% of CagriSema users in REDEFINE 1 vs 39.9% on placebo), though mostly mild to moderate and transient; and it fell short of tirzepatide in a direct comparison.
History & Discovery
Cagrilintide is Novo Nordisk's long-acting take on amylin, the pancreatic beta-cell co-secreted hormone that contributes to postprandial satiety and glucose regulation. Its starting point was pramlintide (Symlin), a short-acting amylin analog developed by Amylin Pharmaceuticals (not Novo Nordisk) and approved by the FDA in March 2005 as an adjunct to insulin for type 1 and type 2 diabetes. Pramlintide demonstrated the clinical viability of amylin agonism but has seen modest real-world uptake because of its requirement for multiple daily injections and its narrow labeled indication. Cagrilintide (internal designation AM833, clinical designation NN9838) was developed specifically to address the dosing-frequency limitation: it is an acylated amylin analog engineered to bind albumin and enable once-weekly subcutaneous administration. Early-phase work published in the late 2010s and early 2020s established its pharmacokinetics, safety, and monotherapy weight-loss signal, with a 2021 Phase 2 dose-finding trial showing 6.0% to 10.8% body weight reduction across weekly doses of 0.3 to 4.5 mg over 26 weeks (placebo 3.0%); the top 4.5 mg dose beat liraglutide 3.0 mg (10.8% vs 9.0%). The program's strategic pivot — and the source of most current attention — is the fixed-dose combination with semaglutide, known as CagriSema. The REDEFINE trial program, including REDEFINE 1 (obesity without diabetes) and REDEFINE 2 (obesity with type 2 diabetes), reported Phase 3 results in 2024–2025: 20.4% to 22.7% mean weight loss in REDEFINE 1 versus 14.9% to 16.1% with semaglutide alone (depending on estimand), and 13.7% to 15.7% in people with type 2 diabetes in REDEFINE 2, positioning the combination as a potential competitor to tirzepatide. Novo Nordisk submitted CagriSema to the FDA in December 2025. In February 2026 the open-label REDEFINE 4 trial showed CagriSema did not meet non-inferiority versus tirzepatide 15 mg (20.2% vs 23.6% at 84 weeks), and the published REIMAGINE trials in type 2 diabetes followed in mid-2026. The 2026 REDEFINE 5 readout in Japan and Taiwan reinforced the pattern in an East Asian population (−18.4% versus −11.9% with semaglutide alone at 68 weeks if taken as intended, with similar GI event rates of 53% vs 51%). Novo Nordisk has not filed cagrilintide as a monotherapy, but after the cagrilintide-only arm of REDEFINE 1 showed 11.8% weight loss, it launched a dedicated Phase 3 program (RENEW) in late 2025.
How It Works
Cagrilintide mimics amylin, a natural hormone that makes you feel full after eating. Combined with semaglutide (which mimics GLP-1), the two hormones work through different brain pathways to provide stronger appetite suppression than either alone.
Cagrilintide is a non-selective agonist of amylin receptors (AMY1 and AMY3, composed of calcitonin receptor + RAMP1 or RAMP3) and of the calcitonin receptor itself, acting in the area postrema and nucleus tractus solitarius. Knockout mouse work shows its weight-lowering effect depends on AMY1 and AMY3. This promotes satiety, slows gastric emptying, and suppresses glucagon. Built on the pramlintide backbone, it carries a C20 fatty diacid attached through a γGlu linker at its N-terminus; albumin binding gives it a half-life of about 159 to 195 hours (roughly a week), allowing once-weekly dosing. When combined with semaglutide's GLP-1R agonism, the dual pathway activation produces complementary and potentially synergistic appetite suppression through distinct hypothalamic and brainstem circuits. A 2026 cross-species brainstem atlas found that long-term cagrilintide treatment works through Calcr/Prlh neurons in the nucleus of the solitary tract, which are conserved from rodents to humans; knocking down Prlh blocked cagrilintide's effects but not semaglutide's in rats.
Evidence Snapshot
Human Clinical Evidence
Substantial for CagriSema. Multiple Phase 3 RCTs (REDEFINE 1, 2 and 5; REIMAGINE 1, 2 and 3) are published, showing 20.4% weight loss at 68 weeks in REDEFINE 1 (22.7% if taken as intended) and HbA1c reductions of about 1.8 to 2.3 points in type 2 diabetes. Two head-to-head trials against tirzepatide (REDEFINE 4, REIMAGINE 4) have reported only by press release. Cagrilintide alone: Phase 2 data plus the REDEFINE 1 monotherapy arm (11.8%), with dedicated Phase 3 (RENEW) under way. No cardiovascular outcomes data yet.
Animal / Preclinical
Strong. Amylin biology and dual-pathway approach well-supported preclinically.
Mechanistic Rationale
Strong. Amylin and GLP-1 pathways are well-characterized individually, and complementary mechanisms are established.
Research Gaps & Open Questions
What the current literature has not yet settled about Cagrilintide:
- 01Cardiovascular outcomes — the REDEFINE 3 trial (7,101 people with established cardiovascular disease, CagriSema vs placebo, major cardiovascular events) has not reported; primary completion is estimated for September 2027. Semaglutide has SELECT data, and tirzepatide's SURPASS-CVOT showed non-inferiority to dulaglutide in type 2 diabetes.
- 02Long-term safety beyond 2 years — completed Phase 3 trials ran 40 to 84 weeks; a 104-week placebo-controlled trial and the REDEFINE 3 outcomes trial (up to about 4.5 years) are ongoing.
- 03Discontinuation trajectory — specific weight-regain and metabolic-regain data after stopping CagriSema, versus stopping semaglutide alone, would inform real-world maintenance strategy.
- 04Responder vs. non-responder biology — a substantial minority of participants in all GLP-1/amylin obesity trials do not achieve clinically meaningful weight loss; predictors of response remain poorly characterized.
- 05Monotherapy value of cagrilintide — Phase 3 RENEW 1 and RENEW 2 (64 weeks, versus placebo) are expected to complete in 2027, and a separate trial is testing whether people who quit GLP-1 drugs because of GI side effects can tolerate cagrilintide. Whether it suits GLP-1 non-responders remains open.
- 06Closing the tirzepatide gap — CagriSema 2.4 mg/2.4 mg missed non-inferiority to tirzepatide 15 mg in REDEFINE 4 (obesity), and in REIMAGINE 4 (type 2 diabetes) it matched tirzepatide on weight but not HbA1c. Whether the higher-dose combination (cagrilintide 2.4 mg with semaglutide 7.2 mg; readout expected first half of 2028) closes the gap is unknown.
- 07Unpublished data — REDEFINE 4, REIMAGINE 4 and 5 and REDEFINE 9 have been reported only by press release, and a warfarin/atorvastatin interaction study completed in 2024 has no posted results.
Forms & Administration
Weekly SC injection. CagriSema: cagrilintide 2.4 mg + semaglutide 2.4 mg given together from a single-use, dual-chamber prefilled pen. Doses increase every 4 weeks over about 16 weeks. Lower combinations (1.0 mg/1.0 mg and 1.7 mg/1.7 mg) have also been tested in Phase 3. All injectable peptides should only be administered under the guidance of a qualified healthcare provider. Never self-administer without clinician oversight.
Dosing & Protocols
The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.
Typical Range
Cagrilintide monotherapy in the Phase 2 dose-finding trial used 0.3, 0.6, 1.2, 2.4, and 4.5 mg weekly (0.16 mg was used only in the Phase 1b combination study), with 2.4 mg selected as the combination dose. CagriSema is formulated as a fixed 2.4 mg cagrilintide plus 2.4 mg semaglutide per weekly injection. Both are administered via weekly subcutaneous injection with gradual dose titration over 16+ weeks to manage GI tolerability.
Frequency
Once weekly subcutaneous injection, identical cadence to semaglutide. Dose escalation in trials stepped up every 4 weeks over the first 16 weeks to limit nausea and vomiting. Phase 3 protocols were flexible: only 57.3% of CagriSema users in REDEFINE 1 were on the top 2.4 mg/2.4 mg dose at 68 weeks (61.9% in REDEFINE 2).
Timing Considerations
No specific timing requirements: can be administered at any time of day, with or without food, and is not tied to exercise timing. Consistency matters more than the specific clock — dose at roughly the same time each day (or same day each week, for weekly protocols) to keep exposure steady.
Cycle Length
Not cycled. Completed efficacy trials ran 40 to 84 weeks; a 104-week trial and the REDEFINE 3 outcomes trial (up to about 4.5 years) are ongoing. Like semaglutide, the expectation is chronic administration for weight maintenance, with weight regain likely upon discontinuation — a class-level feature of GLP-1 and amylin analog obesity therapy.
Protocol Notes
Cagrilintide is investigational as of October 2026; it is not FDA-approved as monotherapy or as part of CagriSema. The FDA is reviewing a CagriSema 2.4 mg/2.4 mg application submitted in December 2025, with a decision expected in Q4 2026. Dosing details here reflect trial protocols, not labeled directions. The US application covers the 2.4 mg/2.4 mg fixed combination, delivered from a dual-chamber pen. Lower combinations (1.0 mg/1.0 mg, 1.7 mg/1.7 mg) and a higher-dose version (cagrilintide 2.4 mg with semaglutide 7.2 mg; readout expected in the first half of 2028) are in Phase 3. The practical dosing story is dominated by GI tolerability. Nausea, vomiting, and constipation are common, especially during titration, and overlap substantially with the semaglutide side effect profile; in REDEFINE 5, GI event rates were similar to semaglutide alone (53% vs 51%). A 2026 BMJ network meta-analysis placed CagriSema among the obesity drugs most often stopped because of adverse events, compared with lifestyle treatment alone. Subcutaneous injection site rotation (abdomen, thigh, upper arm) is standard. There is no indication for intramuscular or intravenous administration.
Cagrilintide and CagriSema are investigational and not FDA-approved as of this writing. Any clinical use outside a registered trial is through compounding, research-chemical channels, or regulatory pathways that sit well outside the standard of care — and compounded amylin analogs lack the quality assurance of the approved sponsor's product. This profile describes trial-program data, not a prescribing recommendation.
Timeline of Effects
Onset
Appetite suppression and reduced caloric intake are expected early, as with other incretin and amylin drugs, but trials report weight change at set visits rather than first onset. Measurable weight loss typically emerges over the first weeks of the 16-week titration.
Peak Effect
Weight loss was still accruing at the end of the main trials. Novo reported no plateau at week 68 in REIMAGINE 2, and the 84-week REDEFINE 4 trial reported 23.0% loss if taken as intended, versus 22.7% at 68 weeks in REDEFINE 1 (different trials, so not a direct comparison). When weight loss levels off with longer use is not yet established.
After Discontinuation
Class-level data from GLP-1 analog discontinuation trials (STEP 4 with semaglutide; similar signals for tirzepatide) suggest substantial weight regain within 12–18 months of stopping, often recovering a majority of the lost weight. The same pattern is expected for CagriSema though long-term discontinuation trials specific to cagrilintide are still accumulating.
Common Questions
What is CagriSema?
CagriSema is a fixed-dose combination of cagrilintide (amylin analogue) and semaglutide (GLP-1 agonist) in a single weekly injection. By targeting two different appetite pathways, it produces greater weight loss than either drug alone.
How does CagriSema compare to tirzepatide?
Both are dual-mechanism weekly injections positioned at the top of the obesity efficacy curve. CagriSema combines GLP-1 (semaglutide) plus amylin (cagrilintide); tirzepatide combines GLP-1 plus GIP. Two head-to-head trials have now reported. In REDEFINE 4 (obesity, open-label, 84 weeks), CagriSema 2.4 mg/2.4 mg produced 20.2% weight loss versus 23.6% with tirzepatide 15 mg counting everyone randomized (23.0% vs 25.5% if taken as intended), and did not meet its non-inferiority goal. In REIMAGINE 4 (type 2 diabetes), CagriSema was non-inferior to tirzepatide 15 mg on weight loss (15.2% vs 15.8%) but not on HbA1c (1.9 vs 2.2 points). At lower doses, CagriSema 1.0 mg/1.0 mg beat tirzepatide 5 mg on weight loss in REIMAGINE 5 (12.4% vs 9.1%). CagriSema is still investigational (FDA decision expected Q4 2026); tirzepatide is FDA-approved as Zepbound for weight management.
Is cagrilintide available as a standalone weight loss drug?
Not yet, but it is now in Phase 3 on its own. In REDEFINE 1, cagrilintide 2.4 mg alone produced 11.8% weight loss at 68 weeks (if taken as intended), versus 16.1% with semaglutide 2.4 mg and 22.7% with CagriSema. Novo Nordisk started the Phase 3 RENEW program in November 2025: RENEW 1 (obesity) and RENEW 2 (obesity with type 2 diabetes), each 64 weeks versus placebo, with completion estimated for May 2027. A separate trial is testing cagrilintide in people who stopped GLP-1 drugs because of GI side effects. Whether monotherapy cagrilintide would be a distinctive option for specific subgroups — such as GLP-1 non-responders or people who cannot tolerate GLP-1 side effects — remains a research gap.
Why does combining cagrilintide with semaglutide work better than either alone?
Cagrilintide and semaglutide engage different appetite circuits. Cagrilintide activates amylin receptors (AMY1, AMY3) and the calcitonin receptor itself. It acts mainly in the brainstem (area postrema and nucleus tractus solitarius), slowing gastric emptying and promoting satiety; in rats, its long-term effect depended on a set of brainstem neurons that semaglutide does not need. Semaglutide activates GLP-1 receptors across hypothalamic and brainstem sites with partially overlapping but distinct downstream signaling. The parallel pathway engagement produces complementary appetite suppression that exceeds what either receptor system delivers on its own — though it also stacks the GI tolerability cost of both mechanisms.
What are the main side effects of CagriSema?
GI side effects dominate the safety profile, similar to other obesity-class injectables: nausea, vomiting, diarrhea, and constipation, especially during the 16-week titration phase. In REDEFINE 1, 79.6% of CagriSema users reported GI events versus 39.9% on placebo. Against semaglutide alone the gap is small: 53% versus 51% in REDEFINE 5. A 2026 meta-analysis found overall and serious adverse events comparable to semaglutide, but more nausea and injection-site reactions, and a 2026 BMJ network meta-analysis linked CagriSema to fatigue (about 92 more cases per 1,000 people over a year than lifestyle treatment alone). Injection site reactions also occur. Class-level cautions around pancreatitis, gallbladder events, and the rodent thyroid C-cell signal are inherited from the GLP-1 component. Long-term safety beyond 2 years has not yet been characterized; the REDEFINE 3 outcomes trial (7,101 participants, up to about 4.5 years) is expected to complete in 2027.
When will CagriSema be approved?
Novo Nordisk submitted CagriSema 2.4 mg/2.4 mg for chronic weight management to the US FDA in December 2025, based on the REDEFINE 1 and REDEFINE 2 trials, and expects an FDA decision in Q4 2026. Approval is not guaranteed, and no other major regulator has approved it as of October 2026.
Does CagriSema work for type 2 diabetes?
In trials, yes. In REIMAGINE 2, CagriSema 2.4 mg/2.4 mg lowered HbA1c by 1.91 points versus 1.75 with semaglutide 2.4 mg at 68 weeks, with 14.2% versus 10.2% weight loss. In REIMAGINE 1 (diet and exercise only), HbA1c fell 1.8 points with 13.8% weight loss at 40 weeks. In REIMAGINE 3 (added to basal insulin), HbA1c fell 2.33 points with no severe hypoglycaemia. Weight loss is smaller in people with diabetes (13.7% in REDEFINE 2). Novo has said it will discuss a diabetes regulatory pathway with authorities.
How long does cagrilintide last in the body?
Its half-life is about 159 to 195 hours (roughly 7 to 8 days), similar to semaglutide's 145 to 165 hours, which is why both are injected once a week. A thorough QT study found no clinically relevant effect on heart rhythm at doses up to 4.5 mg.
Who Cagrilintide Is NOT For
- •Personal or family history of medullary thyroid carcinoma or MEN2 — a class-level caution carried over from GLP-1 agonist labeling because of rodent thyroid C-cell tumor findings; the relevance to amylin analogs specifically is less established but the combination with semaglutide in CagriSema inherits this concern.
- •Pregnancy and breastfeeding — no adequate safety data; standard guidance to avoid.
- •Active severe gastroparesis or gastrointestinal motility disorder — both amylin and GLP-1 agonism slow gastric emptying, and combining them may worsen symptoms; a dedicated gastric-emptying study has finished but not reported results.
- •Personal history of pancreatitis — not a strict contraindication but a caution based on GLP-1 class pharmacovigilance.
- •Known hypersensitivity to cagrilintide, semaglutide, or formulation excipients.
- •Pediatric use — not indicated; a trial of cagrilintide and CagriSema in children and adolescents aged 8 to 18 began in 2026 and has not reported.
Drug & Supplement Interactions
Cagrilintide slows gastric emptying, which may delay absorption of orally administered drugs — particularly those with narrow absorption windows or time-sensitive pharmacokinetics (oral contraceptives, certain antibiotics, thyroid hormone). The clinical magnitude is generally manageable but worth considering for individual medications. Insulin and sulfonylureas: in type 2 diabetes, adding a weight-loss drug to insulin or insulin secretagogues can raise hypoglycemia risk, and dose reduction of the diabetes regimen may be needed as CagriSema titrates up. In REIMAGINE 3, where CagriSema was added to basal insulin for 40 weeks, no severe hypoglycaemia was reported and the authors found no additional hypoglycaemia risk. Other GLP-1 agonists: concurrent use with semaglutide, liraglutide, tirzepatide, or other incretin-class agents alongside CagriSema is not studied and would be redundant or hazardous given overlapping mechanisms. Anti-emetics: routine co-administration is not required but may be used in the titration phase for individuals struggling with nausea. Beyond these class-level considerations, cagrilintide's pharmacokinetic interactions are not extensively characterized in the published literature; albumin binding makes protein-binding drug interactions a theoretical consideration rather than a documented clinical problem. A dedicated 2026 special-population study (Clinical Pharmacokinetics; single doses in 33 people grouped by kidney function and 32 by liver function) reported that renal or hepatic impairment did not produce clinically relevant differences in cagrilintide pharmacokinetics, safety, or tolerability — useful evidence that dose adjustment is unlikely to be required in patients with comorbid kidney or liver disease, a meaningful population in obesity practice. A study of CagriSema's effect on warfarin and atorvastatin levels (NCT06289504) was completed in 2024 but has not posted or published results.
Safety Profile
Common Side Effects
Cautions
- • Not yet FDA-approved
- • GI side effects similar to GLP-1 class
- • Long-term safety data still accumulating
What We Don't Know
Most Phase 3 efficacy trials have reported, but long-term safety and cardiovascular outcomes are not established. The REDEFINE 3 cardiovascular outcomes trial (7,101 people with established cardiovascular disease, up to about 4.5 years) has an estimated primary completion of September 2027.
Legal Status
United States
Cagrilintide and CagriSema are investigational; neither is FDA-approved as of October 2026. Novo Nordisk submitted a New Drug Application for CagriSema 2.4 mg/2.4 mg for adults with overweight or obesity in December 2025, based on REDEFINE 1 and 2, and expects an FDA decision in Q4 2026. Cagrilintide alone is in Phase 3 (RENEW), with no filing yet. Cagrilintide sold by research-chemical vendors is outside any FDA-authorized use and involves the same compounding-pharmacy quality and legal questions that apply to other unapproved peptides. It is not a controlled substance.
International
No major jurisdiction (EMA, MHRA, TGA, Health Canada, PMDA) has approved cagrilintide or CagriSema as of October 2026. Novo Nordisk's mid-2026 report lists only a US decision for CagriSema among its 2026 regulatory milestones. For type 2 diabetes, Novo has said it will discuss the regulatory pathway with authorities.
Sports & Competition
Amylin analogs are not specifically named on the WADA Prohibited List. But because cagrilintide has no current approval from any government health authority, it falls under WADA's S0 'Non-approved substances' category, which prohibits such drugs (including those in clinical development) at all times. That would change for CagriSema only if and when it is approved. Cross-contamination of compounded peptides with prohibited substances is a separate concern.
Regulatory status changes over time. Verify current local rules with a qualified professional.
Myths & Misconceptions
Myth
Cagrilintide is FDA-approved for weight loss.
Reality
It is not. Cagrilintide is investigational as of October 2026, both as monotherapy and as part of CagriSema. The FDA is reviewing CagriSema for weight management, with a decision expected in Q4 2026. Any use outside a registered clinical trial is off-label or extra-regulatory.
Myth
CagriSema is the same as semaglutide with an extra amylin kicker.
Reality
It is a fixed-dose combination of two distinct agonists acting on different receptors (GLP-1R and amylin/calcitonin receptors) with complementary pharmacology. The efficacy gain comes from parallel pathway engagement. Compared directly with semaglutide, overall adverse event rates are broadly similar, but nausea and injection-site reactions are more frequent with the combination.
Myth
Cagrilintide is just a rebranded pramlintide.
Reality
Both are amylin analogs, but cagrilintide is structurally engineered for once-weekly albumin-mediated dosing, while pramlintide requires multiple daily injections. The pharmacokinetic and clinical use profiles are substantially different. Pramlintide is an adjunct to insulin for diabetes; cagrilintide is being developed primarily as an obesity therapeutic.
Myth
Compounded cagrilintide from a wellness clinic is equivalent to the sponsor product.
Reality
Compounded peptide supply chains do not match sponsor-manufactured product on purity, potency consistency, or sterility. For an investigational molecule with no FDA-approved reference standard, the variability is higher, not lower. Compounded cagrilintide also sits outside any approved indication.
Myth
Weight lost on CagriSema is permanent once you stop.
Reality
Class data for GLP-1-containing obesity regimens consistently show substantial weight regain within 12–18 months of discontinuation. CagriSema is expected to behave similarly. Long-term maintenance typically requires ongoing dosing or a structured transition plan, not a one-time course.
Myth
CagriSema beats tirzepatide.
Reality
Not at full doses so far. In the open-label REDEFINE 4 trial, CagriSema 2.4 mg/2.4 mg produced 20.2% weight loss versus 23.6% with tirzepatide 15 mg at 84 weeks and missed its non-inferiority goal. In type 2 diabetes (REIMAGINE 4) it matched tirzepatide 15 mg on weight but not HbA1c. The lower-dose CagriSema 1.0 mg/1.0 mg did beat tirzepatide 5 mg on weight loss in REIMAGINE 5 (12.4% vs 9.1%).
Published Research
36 studiesCagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats.
Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1.
Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis.
Ease of Use, Ease of Learning, and Convenience of the CagriSema Dual-Chamber Pen: Results From a Usability Study in Adults With Overweight, Obesity, or Type 2 Diabetes.
A cross-species atlas of the dorsal vagal complex reveals neural mediators of the effects of cagrilintide on energy balance.
Nature Metabolism 2026: long-term cagrilintide acts through Calcr/Prlh neurons in the brainstem nucleus of the solitary tract, conserved from rodents to humans; knocking down Prlh blocked cagrilintide but not semaglutide in rats.
Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a randomised, double-blind, placebo-controlled, phase 3a study.
Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study.
REIMAGINE 2 (Lancet Diabetes Endocrinol 2026): CagriSema 2.4 mg/2.4 mg lowered HbA1c by 1.91 points versus 1.75 with semaglutide 2.4 mg at 68 weeks in type 2 diabetes.
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.
Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide
2026 Clinical Pharmacokinetics special-population study: single subcutaneous doses of cagrilintide showed no clinically relevant PK, safety, or tolerability differences in participants with renal (n=33) or hepatic (n=32) impairment versus controls; the authors conclude dose adjustment is not warranted, within the limits of small single-dose studies.
Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial
REDEFINE 5 (Lancet Diabetes Endocrinol 2026): in East Asian adults, CagriSema produced 18.4% versus 11.9% weight loss with semaglutide alone at 68 weeks (trial-product estimand), with similar GI event rates (53% vs 51%).
Efficacy and Safety of Cagrilintide and Cagrisema Versus Semaglutide as Anti-Obesity Medications: A Systematic Review, Meta-Analysis and Meta-Regression
Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes
CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1
Structural and mechanistic insights into dual activation of cagrilintide in amylin and calcitonin receptors
Characterization of 0839 - A tool compound for pre-clinical mode-of-action studies of amylin analogues such as cagrilintide
Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity
REDEFINE 1 (NEJM 2025): 3,417 adults without diabetes; CagriSema produced 20.4% mean weight loss at 68 weeks versus 3.0% with placebo, with GI adverse events in 79.6% versus 39.9%, mostly transient and mild to moderate.
Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes
REDEFINE 2 (NEJM 2025): in 1,206 adults with type 2 diabetes, CagriSema produced 13.7% weight loss at 68 weeks versus 3.4% with placebo, and 73.5% reached an HbA1c of 6.5% or less.
Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors
Efficacy and Safety of Cagrilintide Alone and in Combination with Semaglutide (Cagrisema) as Anti-Obesity Medications: A Systematic Review and Meta-Analysis
Amylin analogs for the treatment of obesity without diabetes: present and future
Cagrilintide is not associated with clinically relevant QTc prolongation: A thorough QT study in healthy participants
Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis
Efficacy and safety of GLP-1RAs for people with obesity: A systematic review based on RCT and Bayesian network meta-analysis
Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial
Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity
Does receptor balance matter? - Comparing the efficacies of the dual amylin and calcitonin receptor agonists cagrilintide and KBP-336 on metabolic parameters in preclinical models
Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial
Phase 2 dose-finding trial (Lancet 2021) in 706 adults: weekly cagrilintide 0.3–4.5 mg produced 6.0%–10.8% weight loss at 26 weeks versus 3.0% with placebo and 9.0% with liraglutide 3.0 mg.
Development of Cagrilintide, a Long-Acting Amylin Analogue
Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial
Cagrilintide plus semaglutide for obesity management
AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective Agonists
Novo Nordisk: CagriSema REDEFINE 4 head-to-head results versus tirzepatide (Form 6-K, February 23, 2026)
Open-label 84-week trial: CagriSema 2.4 mg/2.4 mg 20.2% versus tirzepatide 15 mg 23.6% weight loss (23.0% vs 25.5% if taken as intended); non-inferiority not shown. Also confirms the December 2025 FDA submission.
Novo Nordisk: CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial (September 21, 2026)
ClinicalTrials.gov NCT07220642 — RENEW 1 (cagrilintide monotherapy, Phase 3)
ClinicalTrials.gov NCT05669755 — REDEFINE 3 (cardiovascular outcomes)
Popular Stacks Including Cagrilintide
Quick Facts
- Class
- Amylin Analogue
- Tier
- A
- Evidence
- Emerging
- Safety
- Moderate Data
- Updated
- Oct 2026
- Citations
- 36PubMed
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Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.