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

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.