Phase 3 TTT1 trial designed to assess Semaglutide and Dapagliflozin triple therapy in overweight/obese Type 1 Diabetes adults

Achieving optimal glycemic control in Type 1 Diabetes (T1D) is often complicated by insulin-induced weight gain, a significant challenge for many patients. While modern glucose-lowering agents developed for Type 2 Diabetes (T2D), such as GLP-1 receptor agonists and SGLT2 inhibitors, show promise as adjunct therapies, their use in T1D carries risks of hypoglycemia and ketosis. There's a critical need for robust data on combination adjunct therapies that can improve HbA1c without exacerbating these risks, particularly in overweight and obese T1D populations.

This paper describes the design of the Triple Therapy for Type 1 Diabetes (TTT1) trial, an international Phase 3 clinical trial (NCT03899402). Overweight and obese adults with T1D and HbA1c between 7.5% and 11.0% are enrolled. In Period 1 (26 weeks, open-label), participants are randomized 2:1 to receive semaglutide (uptitrated to 1.0 mg weekly) plus insulin, or standard insulin therapy. In Period 2 (26 weeks, double-blind), those on semaglutide and insulin are further randomized to receive dapagliflozin (10 mg daily) or placebo, in addition to semaglutide. Safety outcomes include hypoglycaemia and ketosis.

The TTT1 trial design focuses on assessing the efficacy and safety of combination adjunct therapy. The primary objective is to compare the change in HbA1c on 'triple therapy' (dapagliflozin, semaglutide, and insulin) with 'dual therapy' (placebo, semaglutide, and insulin). Secondary objectives include comparing triple therapy with standard insulin therapy, and dual therapy (semaglutide and insulin) with standard insulin therapy. The trial targets adults with HbA1c between 7.5% and 11.0%. A sample size recalculation, based on masked data analysis, revised the recruitment target from 114 to 82 participants. Safety outcomes, including rates of hypoglycaemia and ketosis, are key endpoints. The study aims to provide clinically useful information on these combination therapies.

The primary objective is to compare change in HbA1c on 'triple therapy' (dapagliflozin, semaglutide and insulin) with 'dual therapy' (placebo, semaglutide and insulin).