Long-term efficacy and safety of tirzepatide in participants with type 2 diabetes with inadequate glycaemic control on metformin and/or sulfonylurea: Post-hoc analysis of SURPASS-4.

AIM: To evaluate the long-term efficacy and safety data at 104 weeks in tirzepatide-treated participants with type 2 diabetes who had inadequate glycaemic control on metformin and/or sulfonylurea. MATERIALS AND METHODS: This post-hoc analysis was based on the SURPASS-4 data (NCT03730662), a multicenter, Phase III trial. Participants were randomised to receive tirzepatide (5, 10, or 15 mg) or insulin glargine. The primary efficacy endpoint was change in HbA1c levels from baseline to 104 weeks. Key secondary endpoints were changes in body weight and the proportion of participants achieving HbA1c <7.0%. Safety endpoints included the incidence of treatment-emergent adverse events (AEs) and hypoglycaemia. RESULTS: This post-hoc analysis included 1,500 participants. At Week 104, participants in the tirzepatide groups had significantly greater mean reduction in HbA1c (5 mg: -2.3%, 10 mg: -2.5%, 15 mg: -2.6%) compared with the insulin glargine group (-1.0%) (p < 0.001). Participants in the tirzepatide groups had significantly greater reduction in body weight (5 mg: -7.6 kg, 10 mg: -10.0 kg, 15 mg: -11.4 kg) compared with the insulin glargine group (2.1 kg) (p < 0.001). Significantly more participants in the tirzepatide group achieved HbA1c <7.0% compared with the insulin glargine group (p < 0.001). The incidence of hypoglycaemia was lower in the tirzepatide groups, and gastrointestinal AEs were mild or moderate in severity. CONCLUSIONS: Tirzepatide significantly improved glycaemic control and body weight reduction compared to insulin glargine over 104 weeks in participants with type 2 diabetes inadequately controlled on metformin and/or sulfonylurea. The safety profile of tirzepatide was acceptable, with a lower incidence of hypoglycaemia than insulin glargine.