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

In adults with type 2 diabetes already on basal insulin, adding once-weekly cagrilintide-semaglutide (CagriSema) reduced HbA1c significantly more than placebo and produced 10-12% bodyweight reduction, with no severe hypoglycaemia.

Late-phase clinical trial — Randomised, double-blind, placebo-controlled, phase 3 trial. Population: Adults with type 2 diabetes (HbA1c 7.0-10.5%) on stable once-daily basal insulin with or without metformin. Sample size: 274 adults. Follow-up: 40 weeks. Interventions: cagrilintide 2.4 mg plus semaglutide 2.4 mg once weekly; cagrilintide 1.0 mg plus semaglutide 1.0 mg once weekly. Cited by 3 other papers.

Mean HbA1c reductions at week 40 were -2.33% (SE 0.08) with cagrilintide-semaglutide 2.4 mg each and -2.10% (0.08) with 1.0 mg each versus -0.66% (0.11) with placebo. Estimated treatment differences versus placebo were -1.68 percentage points (95% CI -1.95 to -1.41) for 2.4 mg and -1.44 (95% CI -1.71 to -1.17) for 1.0 mg, both p<0.0001. Bodyweight reductions of 10-12% were reported. Adverse events were mostly mild or moderate gastrointestinal disorders, occurring in 80%, 71%, and 71% of the respective groups. No severe hypoglycaemia was reported; one death in the 1.0 mg group was not treatment related.

This phase 3 trial provides direct evidence that the cagrilintide-semaglutide combination improves glycaemic control and reduces bodyweight when added to basal insulin in type 2 diabetes. It does not establish cagrilintide's effect as monotherapy, nor does it provide data on long-term cardiovascular outcomes or mortality. Researchers studying cagrilintide will find this a key efficacy and safety reference for the combination.

Key findings

• Cagrilintide-semaglutide 2.4 mg each reduced HbA1c by 2.33% versus 0.66% with placebo (estimated difference -1.68 percentage points, 95% CI -1.95 to -1.41, p<0.0001).
• Cagrilintide-semaglutide 1.0 mg each reduced HbA1c by 2.10% versus 0.66% with placebo (estimated difference -1.44 percentage points, 95% CI -1.71 to -1.17, p<0.0001).
• Bodyweight reductions of 10-12% were reported with cagrilintide-semaglutide.
• Adverse events occurred in 80% (2.4 mg), 71% (1.0 mg), and 71% (placebo) of participants, mostly mild or moderate gastrointestinal disorders.
• No severe hypoglycaemia was reported; one death in the cagrilintide-semaglutide 1.0 mg group was not treatment related.

Limitations

• No active comparator such as semaglutide alone or cagrilintide alone, so the specific contribution of cagrilintide is not isolated.
• Forty weeks is a medium-term follow-up; longer-term efficacy and safety remain unknown.
• Findings are limited to adults with type 2 diabetes already on basal insulin and may not generalise to other populations.
• Authors did not report limitations in the abstract.

The record

• Journal: Lancet (London, England) 408(10549): 38-51
• Published: 2026-06-07
• PMID: 42251856 — DOI: 10.1016/s0140-6736(26)01022-6
• MeSH terms: Humans, Diabetes Mellitus, Type 2, Insulin, Blood Glucose, Hypoglycemic Agents, Drug Therapy, Combination, Double-Blind Method, Aged, Middle Aged, Female, Male, Islet Amyloid Polypeptide, Glycated Hemoglobin, Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide
• Funding: Novo Nordisk AS
• Author countries: Canada, Denmark, India, Italy, USA

Peptide profiles: Cagrilintide.

All indexed evidence: Cagrilintide trials & papers.

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