Cagrilintide

Cagrilintide is a long-acting, injectable amylin analogue designed for once-weekly subcutaneous administration. It was developed to overcome the short duration of earlier amylin therapies such as pramlintide Development of Cagrilintide, a Long-Acting Amylin Analogue+1. The compound acts as a dual amylin and calcitonin receptor agonist, a property that distinguishes it from pure amylin agonists Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors+1.

In human research, cagrilintide has been studied both as monotherapy and in combination with semaglutide (the fixed-dose combination is known as CagriSema). Phase 2 and 3 trials have demonstrated clinically meaningful reductions in body weight and improvements in appetite control, with gastrointestinal side effects being the main tolerability consideration 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+3. The investigational emphasis is on chronic weight management, appetite suppression, and adjunct glycemic control in type 2 diabetes 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+1.

What the research says

• Clinical trials show dose-dependent weight loss with once-weekly dosing 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.
• Combination with semaglutide produces greater weight loss than either agent alone 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+1.
• The mechanism involves central satiety pathways distinct from GLP-1 receptor agonists, which explains the additive effects seen in combination studies A cross-species atlas of the dorsal vagal complex reveals neural mediators of the effects of cagrilintide on energy balance+1.
• Long-term safety and hard outcome data are still emerging, but dedicated studies have found no clinically relevant QT prolongation or need for dose adjustment in renal or hepatic impairment Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide+1.

Cagrilintide reduces food intake and body weight primarily by activating satiety circuits in the brainstem. It is a dual agonist at amylin and calcitonin receptors, which are found in areas like the dorsal vagal complex that control appetite and energy balance Development of Cagrilintide, a Long-Acting Amylin Analogue+2.

Key mechanisms

• Central appetite suppression. In animal studies, cagrilintide activates calcitonin receptor-expressing neurons in the nucleus of the solitary tract. Long-term effects require a specific subset of neurons (PRLH-expressing), and blocking these cells eliminates cagrilintide’s ability to lower weight A cross-species atlas of the dorsal vagal complex reveals neural mediators of the effects of cagrilintide on energy balance.
• Brain amylin receptors 1 and 3. Pharmacological studies point to these receptor subtypes as critical mediators of weight loss Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3.
• Energy intake, not expenditure. Human studies show that cagrilintide-semaglutide combination therapy reduces ad libitum energy intake by more than 60% without measurably slowing gastric emptying at steady state, supporting appetite suppression as the dominant mode of action 1969-LB: Effect of Combined Therapy with Once-Weekly Subcutaneous Cagrilintide 2.4 mg and Semaglutide 2.4 mg (CagriSema) on Energy Intake, Gastric Emptying, and Appetite in Adults with Overweight or Obesity.
• Distinct from GLP-1 pathways. Unlike semaglutide, cagrilintide’s effects are blocked by disrupting Prlh neurons, whereas semaglutide’s effects are not, indicating that their central mechanisms are pharmacologically separate. This explains why combining the two drugs yields additive or synergistic weight loss A cross-species atlas of the dorsal vagal complex reveals neural mediators of the effects of cagrilintide on energy balance.

In practical terms, cagrilintide helps users feel full sooner and stay satisfied longer, reducing overall calorie intake without the stimulant-like effects seen with some older weight-loss drugs.

Clinical trials document several effects of cagrilintide, with the strongest evidence for weight reduction and appetite control.

Weight loss

• Monotherapy. In a phase 2 dose-finding trial, once-weekly cagrilintide produced dose-dependent weight loss in adults with overweight or obesity, with a meaningful reduction observed at 26 weeks 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.
• Combination (CagriSema). Adding cagrilintide to semaglutide consistently led to larger weight losses than semaglutide alone across phase 2 and 3 studies. For example, the REDEFINE 1 trial showed that the combination reduced body weight by 20.4–22.7% on average over 68 weeks .

Appetite and food intake

• Steady-state assessments show large reductions in hunger, prospective food consumption, and ad libitum energy intake. In one study, participants taking CagriSema ate 63% fewer calories compared to placebo 1969-LB: Effect of Combined Therapy with Once-Weekly Subcutaneous Cagrilintide 2.4 mg and Semaglutide 2.4 mg (CagriSema) on Energy Intake, Gastric Emptying, and Appetite in Adults with Overweight or Obesity.

Glycemic control

• In people with type 2 diabetes, cagrilintide-semaglutide improved HbA1c substantially more than semaglutide alone. The REIMAGINE 1 trial (diet and exercise) showed a reduction of 1.8 percentage points, while REIMAGINE 3 (basal insulin) exceeded 2 percentage points Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study+2.

Blood pressure

• The combination also lowered systolic and diastolic blood pressure. In REDEFINE 1, CagriSema reduced blood pressure by about 11/5 mmHg compared to 3/2 mmHg with placebo CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1.

Evidence strength
The weight-loss and glycemic benefits are supported by multiple randomized controlled trials (high evidence). Blood pressure and appetite effects are also from controlled human data. Longer-term cardiovascular outcome studies are ongoing. Most of the evidence comes from the sponsor's development program; independent replication is still limited.

All published human studies administer cagrilintide as a once-weekly subcutaneous injection. The doses are fixed, not adjusted by body weight, and titration is driven by gastrointestinal tolerability.

Representative dosing protocol

• Initiation. Research protocols commonly start at 0.3 mg once weekly for 2 weeks to assess nausea and early fullness.
• Escalation. The dose is increased in 0.3 mg increments every 2–4 weeks until reaching 1.8–2.4 mg weekly. Most trials target a maintenance dose of 2.4 mg 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+1.
• Combination with semaglutide. In CagriSema studies, both drugs are up‑titrated simultaneously to 2.4 mg each 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+1.

Timing and route
Injections can be given at any consistent time each week. No meal‑timing requirement exists because cagrilintide does not primarily delay gastric emptying at steady state 1969-LB: Effect of Combined Therapy with Once-Weekly Subcutaneous Cagrilintide 2.4 mg and Semaglutide 2.4 mg (CagriSema) on Energy Intake, Gastric Emptying, and Appetite in Adults with Overweight or Obesity. Subcutaneous injection is the standard route; no oral or intramuscular protocols are evidence‑based.

Duration
Obesity trials have run 26–68 weeks, reflecting a chronic‑therapy model rather than short cycles 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+1.

Cagrilintide is a lyophilized peptide that requires reconstitution before subcutaneous injection. The following guidance reflects common practices for research peptides; no published trial used end‑user reconstitution.

Diluent and handling

• Use bacteriostatic water for multi‑dose vials. Sterile water may be used if the entire vial will be used within a short period.
• Add the diluent gently, allowing it to run down the vial wall. Swirl slowly to dissolve; do not shake or vortex, as vigorous agitation can damage the peptide.
• Once reconstituted, store the solution at 2–8 °C (refrigerated) and protect from light. Do not freeze after reconstitution.

Stability

• In vitro metabolism studies show cagrilintide degrades via N‑ and C‑terminal cleavage, so cold storage is important In vitro metabolic profiling of weight-loss-inducing amylin receptor agonists in the context of preventive doping research.
• Typical shelf life for reconstituted peptides: 28 days at 2–8 °C when using bacteriostatic water; 7–14 days with sterile water. Discard if the solution becomes cloudy or contains particles.

Concentration and dosing
The interactive calculator on this page will help determine the exact volume to draw based on the desired dose and the concentration you prepare. As a general principle, higher concentrations keep injection volumes small and are often preferred.

Because cagrilintide is a peptide, it is not metabolized by CYP enzymes. Its primary interactions are pharmacodynamic, stemming from appetite suppression and weight loss.

Drug classes to watch

• Insulin and sulfonylureas. As food intake falls, glucose levels drop, raising the risk of mild hypoglycemia. Reduce doses proactively if meals become smaller 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.
• GLP‑1 receptor agonists. Combining cagrilintide with semaglutide is well‑studied and effective, but it amplifies gastrointestinal side effects. Avoid adding full‑dose GLP‑1 agonists without medical supervision 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+1.
• Antihypertensives and diuretics. Weight loss from cagrilintide‑containing regimens can lower blood pressure significantly; patients on multiple antihypertensives may need dose reductions CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1.
• Oral medications requiring food. Marked appetite suppression may cause reduced adherence to food‑dependent drugs. Monitor such drugs closely.
• QT‑prolonging drugs. A dedicated study found no clinically relevant QTc prolongation even at supratherapeutic doses (4.5 mg), so additional QT monitoring is not required solely because of cagrilintide Cagrilintide is not associated with clinically relevant <scp>QTc</scp> prolongation: A thorough <scp>QT</scp> study in healthy participants.

Supplements

• Berberine, chromium, etc. These may have additive glucose‑lowering effects when combined with diabetes medications.
• Fiber supplements. Can increase fullness and bloating; use with extra fluids.
• Alcohol. Can worsen nausea and dehydration, especially during dose escalation.

Renal or hepatic impairment
Single‑dose studies found no need for routine dose adjustment Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide. However, dehydration from GI side effects may transiently affect kidney function.

Cagrilintide is designed for chronic use. Human trials have administered it continuously for up to 68 weeks without evidence of tolerance or tachyphylaxis 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+1. The once‑weekly pharmacokinetic profile also argues against short “on/off” cycling, because drug levels remain elevated for weeks after a dose Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide.

When a break may be considered

• Persistent gastrointestinal intolerance. If nausea or vomiting persist despite slow escalation, a pause of 1–2 weeks can reset tolerability. Most users restart at a lower dose 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+1.
• Plateauing weight loss. If appetite suppression wanes after months at a stable dose, a planned reassessment (e.g., 2–4 week break) is sometimes used in practice, though it is not supported by formal studies.
• Post‑goal transition. After achieving target weight, tapering the dose over 4–8 weeks may help prevent rapid appetite rebound. This is based on practitioner consensus rather than direct trial evidence.

What the research does not support

• Mandatory “receptor resensitization” cycles. There is no signal that amylin/calcitonin receptors downregulate in a way that requires cycling.
• Brief (1‑week off) cycles. Due to the long half‑life, such short breaks are unlikely to meaningfully reset the system.

In short, continuous therapy is the evidence‑based approach. Cycling is reserved for managing side effects or transitions, not for preserving efficacy.

Cagrilintide has been studied most extensively in combination with semaglutide, where it consistently enhances weight loss. Other combinations are largely experimental.

Cagrilintide + semaglutide (CagriSema)

• This is the best‑documented stack. Phase 3 trials show it reduces body weight and HbA1c more than semaglutide alone. The mechanisms are complementary: semaglutide works through GLP‑1 receptors, while cagrilintide targets amylin/calcitonin pathways Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity+3.
• Side effects, mainly nausea and vomiting, are more frequent than with either drug alone, so slower titration is often used.

Cagrilintide + tirzepatide

• Animal studies suggest additive effects, but no human trial has been published 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. In practice, using two potent appetite‑suppressing agents would likely increase gastrointestinal distress and is considered experimental.

Cagrilintide + other incretin‑based agents

• Adding cagrilintide to GLP‑1 agonists other than semaglutide (e.g., liraglutide, dulaglutide) has not been formally studied. Given the overlapping gastrointestinal side‑effect profiles, caution is warranted.

Cagrilintide + growth hormone secretagogues

• Anecdotal reports describe stacking with peptides like CJC‑1295/Ipamorelin to offset lean‑mass loss during aggressive dieting. However, there is no published evidence, and the injection burden can be high.

When stacking, introduce one compound at a time and titrate slowly to identify the source of any side effects.

United States
Cagrilintide is not FDA‑approved as a standalone product. It is in late‑stage clinical development, with phase 3 data available for the fixed‑dose combination with semaglutide (CagriSema) in obesity and type 2 diabetes Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide+2. The development program follows a typical biologic prescription‑drug pathway. No DEA scheduling or controlled‑substance status is described in the corpus.

International
Multinational phase 3 programs (REIMAGINE, REDEFINE) have been conducted, including a dedicated study in Japan and Taiwan 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. However, no marketing authorization by the EMA, MHRA, TGA, or other regulators is documented in the provided sources. The compound is therefore considered investigational globally.

Anti‑doping
Cagrilintide has not been formally listed as prohibited by WADA, but it is firmly on the radar of anti‑doping scientists. A 2026 analytical paper characterized its metabolites and argued that amylin receptor agonists warrant inclusion in sports drug testing In vitro metabolic profiling of weight-loss-inducing amylin receptor agonists in the context of preventive doping research. Predicted metabolites were confirmed in animal plasma, meaning targeted testing is feasible. Athletes should assume that use could be detected if monitoring programs advance.

Gastrointestinal effects
Nausea is the most common side effect, reported in a majority of users during dose escalation. Vomiting, early satiety, and constipation also occur, especially when combined with semaglutide. Events are typically mild‑to‑moderate and decrease over time 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+1. In phase 3 CagriSema trials, adverse events were reported in over 80% of participants, with GI disorders predominating Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study.

Cardiac safety
A dedicated QT study found no clinically relevant QTc prolongation at doses up to 4.5 mg weekly, arguing against a direct arrhythmia risk Cagrilintide is not associated with clinically relevant <scp>QTc</scp> prolongation: A thorough <scp>QT</scp> study in healthy participants.

Kidney and liver
Single‑dose studies in renal and hepatic impairment showed no significant changes in exposure, suggesting no mandatory dose adjustment Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide. Dehydration from nausea, however, can secondarily affect kidney function.

Metabolic
Cagrilintide alone is unlikely to cause hypoglycemia, but risk increases when combined with insulin or sulfonylureas. Blood pressure reductions are expected; patients on antihypertensives may need dose reductions CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1.

Contraindications

• Absolute: prior serious hypersensitivity; inability to maintain hydration due to vomiting; pregnancy (no safety data).
• Relative: severe gastroparesis, eating disorders, frailty/sarcopenia risk, concurrent insulin/secretagogues without glucose monitoring.

Monitoring
Before starting: weight, blood pressure, renal/liver function, fasting glucose. During titration: weekly GI symptom checks, fluid intake, and blood pressure. If diabetic, monitor glucose closely during dose changes.