Dual versus monotherapy with SGLT2 inhibitor and GLP-1 receptor agonist: PRECIDENTD pragmatic randomized trial.

Abstract

BackgroundDual therapy with sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) is frequently recommended. We compared rates of medication initiation and discontinuation between participants assigned to treatment with a single medication class or dual therapy in the feasibility phase of the PREvention of CardIovascular and DiabEtic kidNey disease in Type 2 Diabetes (PRECIDENTD) pragmatic trial.MethodsPRECIDENTD randomly assigned participants with type 2 diabetes (T2D) and ASCVD or high ASCVD risk to fill prescriptions for SGLT2i, GLP-1RA, or dual therapy (1:1:1) using their own insurance. Analyses compared medication fill and discontinuation rates of assigned medication(s), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical and Mental Health Scores, and Modified Kansas City Cardiomyopathy Questionnaire (mKCCQ)-12 between the combined monotherapy (SGLT2i or GLP-1RA) and dual therapy (SGLT2i and GLP-1RA) groups.ResultsThis report includes 173 insured participants [median age 67 years (IQR 62, 72), 46% female, 35% non-White, 67% with ASCVD]; 113 assigned to monotherapy and 60 to dual therapy. Monotherapy vs dual therapy fill rates were 84% vs 53% (P < .001) 4 months after randomization and 87% vs 68% overall (P = .004) during 10-month median follow-up. Of those who filled medication, 22% in monotherapy and 49% in dual therapy discontinued a study medication (P = .002), mostly due to side effects. PROMIS and mKCCQ-12 scores showed no change.ConclusionsDespite efforts to facilitate medication uptake in the feasibility phase of the PRECIDENTD pragmatic trial, barriers to initiation and ongoing use challenge the use of combination SGLT2i and GLP-1RA in T2D.Trial registrationClinicalTrials.gov, NCT05390892, https://clinicaltrials.gov/study/NCT05390892.