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

Abstract

Background: Dual 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.

Methods: PRECIDENTD 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.

Results: This 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.

Conclusions: Despite 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 registration: ClinicalTrials.gov, NCT05390892, https://clinicaltrials.gov/study/NCT05390892.