Continuous Glucose Monitoring Profiles and Health Outcomes After Dapagliflozin Plus Saxagliptin vs Insulin Glargine

Abstract Context Glycemic variability and hypoglycemia during diabetes treatment may impact therapeutic effectiveness and safety, even when glycated hemoglobin (HbA1c) reduction is comparable between therapies. Objective We employed masked continuous glucose monitoring (CGM) during a randomized trial of dapagliflozin plus saxagliptin (DAPA + SAXA) vs insulin glargine (INS) to compare glucose variability and patient-reported outcomes (PROs). Design 24-week substudy of a randomized, open-label, 2-arm, parallel-group, phase 3b study. Setting Multicenter study (112 centers in 11 countries). Patients 283 adults with type 2 diabetes (T2D) inadequately controlled with metformin ± sulfonylurea. Interventions DAPA + SAXA vs INS. Main outcome measures Changes in CGM profiles, HbA1c, and PROs. Results Changes from baseline in HbA1c with DAPA + SAXA were similar to those observed with INS, with mean difference [95% confidence interval] between decreases of −0.12% [−0.37 to 0.12%], P = .33. CGM analytics were more favorable for DAPA + SAXA, including greater percent time in range (> 3.9 and ≤ 10 mmol/L; 34.3 ± 1.9 vs 28.5 ± 1.9%, P = .033), lower percent time with nocturnal hypoglycemia (area under the curve ≤ 3.9 mmol/L; 0.6 ± 0.5 vs 2.7 ± 0.5%, P = .007), and smaller mean amplitude of glycemic excursions (−0.7 ± 0.1 vs −0.3 ± 0.1 mmol/L, P = .017). Improvements in CGM were associated with greater satisfaction, better body weight image, less weight interference, and improved mental and emotional well-being. Conclusion DAPA + SAXA and INS were equally effective in reducing HbA1c at 24 weeks, but people with T2D treated with DAPA + SAXA achieved greater time in range, greater reductions in glycemic excursions and variability, less time with hypoglycemia, and improved patient-reported health outcomes.