Efficacy and safety of co-administered cagrilintide and semaglutide (CagriSema) once weekly versus placebo in participants with type 2 diabetes and painful diabetic peripheral neuropathy

A clinical trial is testing whether a weekly injection of two drugs combined—cagrilintide and semaglutide, called CagriSema—can relieve the burning, stabbing nerve pain that affects roughly one in five people with type 2 diabetes. Painful diabetic peripheral neuropathy (pDPN) has no approved treatments that target the underlying nerve damage. Current painkillers often provide only modest relief and can cause serious side effects. This proof-of-concept study randomly assigns 134 participants to receive either CagriSema or a placebo for several weeks, with neither patients nor doctors knowing who gets which. The trial measures changes in pain scores and tracks safety. If CagriSema proves effective, it would offer the first therapy that simultaneously addresses both the metabolic drivers of diabetes and the nerve pain itself—potentially replacing the current trial-and-error approach with a single, once-weekly injection. Because semaglutide is already widely used for diabetes and weight management, and cagrilintide is a related hormone analogue, the combination could be rapidly repurposed if results are positive. The study is funded by the National Institute for Health and Care Research.