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Insulin, Semaglutide and Dapagliflozin in Adults With Type 1 Diabetes: Design and Methods of Triple Therapy for Type 1 Diabetes (TTT1)-An International Phase 3 Clinical Trial.

Joseph G Timmons·Husam Ghanim·James G Boyle·Nicola Greenlaw·Ajay Chaudhuri·Manav A Batra·Robert S Lindsay·Lisa Jolly·Caroline Bonner·Alex McConnachie·John R Petrie·Paresh Dandona
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Abstract

AIMS: Attaining target glycaemia can be a challenge in Type 1 Diabetes (T1D) due to insulin-induced weight gain. Adjunct therapy with modern glucose-lowering agents developed for type 2 diabetes (T2D) has great potential but may be insufficiently efficacious and carries risks of hypoglycaemia and ketosis. We designed the first Phase 3 clinical trial to assess the efficacy and safety of adding a Glucagon-Like Peptide 1 receptor agonist (GLP-1RA) and a Sodium-Glucose Co-transporter (SGLT2) Inhibitor to insulin therapy in overweight and obese adults with T1D and glycaemia above target (HbA1c 7.5%-11.0% inclusive) (NCT03899402). MATERIALS AND METHODS: In Period 1, participants are randomized 2:1 (open label) for 26 weeks to semaglutide and insulin (uptitrated to 1.0 mg weekly) or standard insulin therapy. In Period 2, those randomized to semaglutide and insulin in Period 1 are further randomized (double-blind) for 26 weeks to dapagliflozin (10 mg daily) or placebo, in addition to semaglutide. The primary objective is to compare change in HbA1c on 'triple therapy' (dapagliflozin, semaglutide and insulin) with 'dual therapy' (placebo, semaglutide and insulin). Secondary objectives include comparisons of triple therapy with standard insulin therapy and dual therapy (semaglutide and insulin) with standard insulin therapy. Safety outcomes include hypoglycaemia and ketosis. A sample size recalculation during the trial based on analysis of masked data revised the original recruitment target from 114 to 82 participants. CONCLUSION: The TTT1 trial will provide clinically useful information on combination adjunct therapy in the treatment of T1D.

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HumansSemaglutideDiabetes Mellitus, Type 1Glucagon-Like PeptidesDrug Therapy, CombinationHypoglycemic AgentsGlucosidesInsulinBenzhydryl CompoundsAdultFemaleMaleDouble-Blind MethodGlycated HemoglobinMiddle AgedSodium-Glucose Transporter 2 InhibitorsBlood GlucoseTreatment OutcomeHypoglycemiaObesityadjunct therapyadjunctive therapycombination therapy dapagliflozinketosissemaglutidetype 1 diabetesJournal ArticleRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study

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Joseph G Timmons, Husam Ghanim, James G Boyle, Nicola Greenlaw, Ajay Chaudhuri, Manav A Batra, Robert S Lindsay, Lisa Jolly, Caroline Bonner, Alex McConnachie, John R Petrie, Paresh Dandona. 2026-07-19. Insulin, Semaglutide and Dapagliflozin in Adults With Type 1 Diabetes: Design and Methods of Triple Therapy for Type 1 Diabetes (TTT1)-An International Phase 3 Clinical Trial.. https://doi.org/10.1111/dom.71076

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Adult subjectBenzhydryl Compounds subjectBlood Glucose subjectClinical Trial, Phase III subjectDouble-Blind Method subjectDrug Therapy, Combination subjectFemale subjectGlucosides subjectHumans subjectJournal Article subjectMale subjectMiddle Aged subjectMulticenter Study subjectObesity subjectRandomized controlled trials study

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