ADD2Dia: Real-World Clinical Effectiveness of Adding a Sodium-Glucose Cotransporter 2 Inhibitor to Gliclazide-Based Therapy in Type 2 Diabetes.

INTRODUCTION: This study investigated the real-world clinical effectiveness and tolerability of adding a sodium-glucose cotransporter 2 inhibitor (SGLT2i) to gliclazide modified release (MR)-based therapy in a sample of patients with type 2 diabetes (T2D) across five countries, and its value as an effective and well-tolerated strategy in T2D management in a diverse patient population, including those at high risk. METHODS: This non-interventional, retrospective chart review study included patients with T2D treated with gliclazide MR-based therapy and an SGLT2i for at least 60 days. The primary outcome was change in glycated hemoglobin (HbA1c) levels. Secondary outcomes included treatment patterns, proportion of patients achieving an HbA1c target < 7%, changes in lipid profile, blood pressure, weight, new-onset comorbidities, and adverse events of special interest (AESI). RESULTS: A total of 537 patients (47.7% female, mean age of 59.2 years, mean disease duration 10.0 years) were included, of whom 75.4% were obese/overweight and 15.1% had atherosclerotic cardiovascular disease (ASCVD). At baseline, HbA1c was uncontrolled (≥ 7%) in 87.2% of patients (mean HbA1c of 8.7% [SD 1.7]). Mean HbA1c reductions were - 1.1% (SD 1.8) at 6 months, - 0.7% (SD 1.9) at 2.4 years, and - 0.6% (SD 1.7) at 3 years. The proportion of patients with HbA1c < 7% increased from 12.8% at baseline to 29.3% at least once during follow-up. Mean body weight decreased by 1.7 kg (95% CI - 2.2, - 1.3). AESIs were reported in 40 patients (7.4%) with urinary tract infections being the most common (6.8%). CONCLUSION: The first real-world study of the long-term combination of gliclazide MR and SGLT2i demonstrated its value as an effective and well-tolerated strategy in T2D management, particularly in high-risk populations. This combination provided clinically meaningful and sustained HbA1c reductions and improved cardiometabolic parameters in a diverse T2D population, with very few adverse events. These results align with current guidelines emphasizing the importance of early combination treatment and multifactorial risk management in T2D and highlight the need to address late treatment intensification indicative of clinical inertia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT06708091.