Cagrilintide is a long-acting synthetic amylin analog given by once-weekly injection, developed primarily for weight loss and glycemic control — most notably in combination with semaglutide as the dual agent CagriSema.
What it does
Amylin is a 37-amino acid hormone co-released with insulin from the pancreas after meals. Cagrilintide mimics amylin by binding amylin receptors — protein complexes formed by the calcitonin receptor (CALCR) pairing with accessory proteins called RAMPs — concentrated in the area postrema and hypothalamus, brain regions that regulate hunger and satiety Yi-Min 2026. This central signaling reduces appetite through a pathway that is anatomically and biochemically distinct from GLP-1 (glucagon-like peptide-1), the target of drugs like semaglutide Mokhtar 2026.
Beyond appetite suppression, cagrilintide slows gastric emptying — the rate at which food leaves the stomach — which extends the feeling of fullness after meals and blunts the spike in blood glucose that follows eating Won 2026. It also suppresses post-meal glucagon secretion, a hormone that raises blood sugar when it should be falling A 2025.
The acylation (fatty acid chain attachment) engineered into cagrilintide extends its half-life to roughly 7–8 days, enabling once-weekly dosing Sanaz 2025. Because amylin and GLP-1 act on separate receptor systems, combining cagrilintide with semaglutide in a single injection — branded CagriSema — produces additive appetite reduction that neither agent achieves alone Mie 2025.
What the evidence shows
Weight loss (obesity) Multiple Phase 2 and Phase 3 human trials; robust data for CagriSema combination, moderate for cagrilintide monotherapy
In the REDEFINE 1 Phase 3 trial, CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg weekly) produced roughly 22–25% body weight loss over 68 weeks in adults with obesity PubMed 41259764. A systematic review and meta-analysis of randomized controlled trials confirmed that CagriSema outperforms semaglutide monotherapy on weight reduction, with GRADE assessment rating the evidence as moderate-to-high quality PubMed 41759565. A separate meta-analysis found consistent superiority of cagrilintide-containing regimens over semaglutide alone for both weight and metabolic outcomes PubMed 41834765.
Cagrilintide monotherapy also reduces body weight dose-dependently, though the effect size is smaller than the combination A 2025. In East Asian populations, the REDEFINE 5 trial showed CagriSema significantly outperformed semaglutide alone on weight loss, with a broadly similar safety profile PubMed 42009015. Phase 3 REDEFINE trials are still enrolling or reporting, so the full long-term picture — including durability after discontinuation — is not yet available NCT05567796.
Glycemic control (type 2 diabetes) Phase 2–3 human data; strong signal for HbA1c reduction, head-to-head with tirzepatide ongoing
CagriSema lowers HbA1c (a 3-month average of blood glucose levels) meaningfully in adults with type 2 diabetes treated on metformin, though direct comparison to tirzepatide is still in progress NCT06221969. Glucagon suppression and slower gastric emptying both contribute to the glycemic effect, on top of the weight-loss-mediated improvements in insulin sensitivity Won 2026. Predictive modeling suggests amylin-pathway therapies may offer distinct glycemic advantages in patients who do not respond fully to GLP-1 alone A 2025.
Blood pressure reduction Emerging human data from REDEFINE 1; mechanism not fully characterized
A secondary analysis of REDEFINE 1 found CagriSema reduced systolic blood pressure significantly compared to placebo in adults with overweight or obesity Subodh 2026. Whether this is driven primarily by weight loss or by a direct vascular effect of amylin receptor activation is unresolved. The amylin system has known interactions with the renin-angiotensin system (which regulates blood pressure), introducing both potential benefit and a theoretical safety consideration that warrants further study A 2026.
Preservation of energy expenditure during weight loss Strong rodent evidence; human metabolic data limited
In rat studies, CagriSema drove weight loss almost entirely through reduced food intake rather than a drop in metabolic rate — a meaningful distinction because most caloric restriction causes the body to compensate by burning fewer calories Mie 2025. Whether this energy expenditure preservation translates reliably to humans has not been confirmed in dedicated metabolic ward studies, but it is a plausible mechanism worth watching as longer-term human data accumulate.
How it's used
In Phase 2 and 3 clinical trials, cagrilintide is dosed subcutaneously (injected under the skin) once weekly. Doses have ranged from 0.3 mg/week at the low end of dose-escalation protocols up to 4.5 mg/week at the high end; the 2.4 mg/week dose is used in the CagriSema combination studied in REDEFINE trials PubMed 41259764. Injection is typically on the same day each week, into the abdomen, thigh, or upper arm. In combination protocols, cagrilintide and semaglutide are co-formulated in a single injection. Dose escalation over several weeks is standard to reduce gastrointestinal side effects. Cagrilintide is not approved for clinical use as of mid-2025; all dosing information comes from trial protocols and self-reported use, not approved labeling.
Side effects and safety
The most common adverse effects reported across trials are gastrointestinal: nausea, diarrhea, constipation, vomiting, and abdominal discomfort PubMed 41834765. These are typically dose-dependent and most pronounced during dose escalation, similar to the GLP-1 drug class. Injection site reactions occur but are generally mild PubMed 41759565. More serious events — pancreatitis and gallbladder disease — have been reported at low rates consistent with the GLP-1 class; causality specific to the amylin component has not been established Won 2026. The amylin system interacts with the renin-angiotensin system, raising theoretical cardiovascular questions that have not been resolved A 2026. Hypoglycemia risk increases when cagrilintide is combined with insulin. Long-term safety data beyond two years, effects in pregnancy, and safety in severe kidney disease are not yet established PubMed 41375628. Cagrilintide has also been flagged in preventive doping research as a detectable compound in anti-doping contexts PubMed 41702251.
Bottom line
Cagrilintide, especially as CagriSema, represents the most substantial weight-loss signal seen in a pharmacological agent to date — Phase 3 data showing ~22–25% body weight reduction in people with obesity is a meaningful clinical result PubMed 41259764. The evidence base is growing rapidly but still maturing; it is not approved, long-term safety data are incomplete, and most access outside trials is off-label. People with gastroparesis, those on insulin, or anyone pregnant should avoid it.