K4 Elite
K4 Elite
Cagrilintide is a long-acting amylin analogue developed by Novo Nordisk for once-weekly subcutaneous administration. As monotherapy it has been studied in a Phase 1b multiple-ascending-dose trial and a 26-week Phase 2 dose-finding RCT (Lau et al., Lancet 2021); most subsequent evidence concerns its fixed-dose co-administration with semaglutide 2.4 mg (CagriSema) in Phase 2 and Phase 3 trials (REDEFINE and REIMAGINE programmes), several of which included a cagrilintide-alone arm. Cagrilintide is investigational and not approved by any regulator.
Each row records what a published study did: who it enrolled, the regimen it administered to those subjects, and what it reported. These are historical study descriptions, not protocols to follow.
| Study | Population | Regimen as reported | Primary findings |
|---|---|---|---|
| Lau et al., Lancet 2021 (Phase 2 dose-finding, cagrilintide monotherapy) Registry: NCT03856047
|
Adults without diabetes with BMI >=30, or >=27 with hypertension or dyslipidaemia (n=706 randomised; 57 sites, ten countries) | Participants were randomly assigned to once-weekly subcutaneous cagrilintide 0.3, 0.6, 1.2, 2.4 or 4.5 mg, once-daily liraglutide 3.0 mg, or volume-matched placebo for 26 weeks, including a dose-escalation period of up to 6 weeks, followed by 6 weeks off treatment. | Mean percentage weight reductions from baseline to week 26 were 6.0%-10.8% with cagrilintide 0.3-4.5 mg versus 3.0% with placebo; cagrilintide 4.5 mg produced 10.8% versus 9.0% with liraglutide 3.0 mg. |
| Enebo et al., Lancet 2021 (Phase 1b, cagrilintide with semaglutide 2.4 mg) Registry: NCT03600480
|
Otherwise healthy adults aged 18-55 with BMI 27.0-39.9 kg/m2 (n=96 randomised; single US centre) | In six sequential cohorts, participants were randomly assigned 3:1 to once-weekly subcutaneous cagrilintide (0.16, 0.30, 0.60, 1.2, 2.4 or 4.5 mg) or placebo, each combined with once-weekly semaglutide 2.4 mg; doses were co-escalated at 4-week intervals over 16 weeks, held at target for 4 weeks, then followed up for 5 weeks. | Of 566 adverse events in 92 participants, 37% were gastrointestinal; most were mild to moderate and the proportion with at least one event was similar across groups. Cagrilintide exposure was dose-proportional and did not affect semaglutide exposure or elimination. |
| Frias et al., Lancet 2023 (Phase 2, CagriSema in type 2 diabetes) Registry: NCT04982575
|
Adults with type 2 diabetes and BMI >=27 kg/m2 on metformin with or without an SGLT2 inhibitor (n=92; 17 US sites) | Participants were randomly assigned 1:1:1 to once-weekly subcutaneous CagriSema, semaglutide, or cagrilintide, all escalated to 2.4 mg, for 32 weeks. | Mean change in HbA1c at week 32 was -2.2 percentage points with CagriSema, -1.8 with semaglutide and -0.9 with cagrilintide; body weight changed by -15.6%, -5.1% and -8.1% respectively. |
| REDEFINE 1 — Garvey et al., NEJM 2025 (Phase 3a, CagriSema vs components vs placebo) Registry: NCT05567796
|
Adults without diabetes with BMI >=30, or >=27 with at least one obesity-related complication (n=3,417 randomised) | Participants were randomly assigned 21:3:3:7 to once-weekly cagrilintide 2.4 mg plus semaglutide 2.4 mg, semaglutide 2.4 mg alone, cagrilintide 2.4 mg alone, or placebo, plus lifestyle intervention, for 68 weeks. | Estimated mean percent change in body weight from baseline to week 68 was -20.4% with cagrilintide-semaglutide versus -3.0% with placebo (treatment-policy estimand). |
| REDEFINE 2 — Davies et al., NEJM 2025 (Phase 3a, CagriSema in type 2 diabetes) Registry: NCT05394519
|
Adults with BMI >=27, HbA1c 7-10% and type 2 diabetes (n=1,206 randomised; 12 countries) | Participants were assigned 3:1 to once-weekly cagrilintide-semaglutide (2.4 mg each) or placebo, with lifestyle intervention, for 68 weeks. | Estimated mean change in body weight from baseline to week 68 was -13.7% with cagrilintide-semaglutide versus -3.4% with placebo; gastrointestinal adverse events were reported by 72.5% versus 34.4%. |
| Thorough QT study, Diabetes Obes Metab 2024 (healthy volunteers) Registry: NCT05804162
|
Healthy participants (n=105; 53 cagrilintide, 52 placebo) | Participants were randomised to once-weekly subcutaneous cagrilintide dose-escalated to 4.5 mg, or placebo; placebo participants also received a single 400 mg oral moxifloxacin dose as positive control. | No clinically relevant QTcF prolongation occurred after the last cagrilintide 4.5 mg dose; upper limits of the two-sided 90% CIs for placebo-adjusted change were below 10 ms at all time points. |
Effects recorded in the cited reports. Frequencies are those the source reported, in the population that source studied.
| Effect | Frequency / context | Source |
|---|---|---|
| Gastrointestinal adverse events (nausea, constipation, diarrhoea) | 41%-63% with cagrilintide 0.3-4.5 mg vs 32% placebo over 26 weeks (Lau et al., Lancet 2021 Phase 2). | Once-weekly cagrilintide for weight management in people with overweight and obesity: ... dose-finding phase 2 trial ↗ |
| Nausea | 20%-47% with cagrilintide 0.3-4.5 mg vs 18% placebo (Lau et al., Lancet 2021 Phase 2). | Once-weekly cagrilintide for weight management in people with overweight and obesity: ... dose-finding phase 2 trial ↗ |
| Administration-site reactions | Listed among the most frequent adverse events in the Phase 2 monotherapy trial (Lau et al., Lancet 2021); percentages not given in the abstract. | Once-weekly cagrilintide for weight management in people with overweight and obesity: ... dose-finding phase 2 trial ↗ |
| Permanent treatment discontinuation | 10% overall across groups, mostly due to adverse events (4%), in the Phase 2 monotherapy trial (Lau et al., Lancet 2021). | Once-weekly cagrilintide for weight management in people with overweight and obesity: ... dose-finding phase 2 trial ↗ |
| Any adverse event (cagrilintide-alone arm) | 80% (24/30) in the cagrilintide 2.4 mg arm vs 68% CagriSema and 71% semaglutide in the 32-week Phase 2 type 2 diabetes trial; mild or moderate gastrointestinal events most common, no level 2 or 3 hypoglycaemia (Frias et al., Lancet 2023). | Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: ... phase 2 trial ↗ |
| Gastrointestinal adverse events with CagriSema (combination, not cagrilintide alone) | 79.6% with cagrilintide-semaglutide vs 39.9% placebo in REDEFINE 1 (NEJM 2025); 72.5% vs 34.4% in REDEFINE 2 (NEJM 2025); mainly transient and mild to moderate. | Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity ↗ |
| QTc prolongation | Not observed: no clinically relevant QTcF prolongation at cagrilintide 4.5 mg in a thorough QT study (n=105). | Cagrilintide is not associated with clinically relevant QTc prolongation: A thorough QT study in healthy participants ↗ |
Interactions documented in trial reports, prescribing information or pharmacology references.
| Agent | Type | Note | Source |
|---|---|---|---|
| Semaglutide 2.4 mg | pharmacokinetic (co-administration study) | In the Phase 1b trial, cagrilintide exposure was proportional to dose and did not affect semaglutide exposure or elimination; gastrointestinal events accounted for 37% of adverse events with the combination. | Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg ... phase 1b trial ↗ |
| Renal or hepatic impairment (special populations, not a drug interaction) | pharmacokinetic | Single-dose studies (cagrilintide 0.6 mg or 0.9 mg) found no clinically relevant differences in AUC or Cmax across normal, mild, moderate or severe renal or hepatic impairment; no serious adverse events were reported. | Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide ↗ |
Exclusions and label contraindications recorded in the cited sources.