Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are widely prescribed for type 2 diabetes, yet their long-term effectiveness in routine practice remains uncertain. A large real-world analysis, published in Diabetes, Obesity and Metabolism, used Komodo’s Healthcare Map to evaluate treatment failure among 237,295 U.S. adults initiating SGLT2i therapy between 2016 and 2024. Treatment failure was defined as discontinuation, therapy change, or persistent uncontrolled HbA1c without treatment action.

Overall, 77.3% of patients experienced treatment failure, with a median time of 9.1 months. Discontinuation accounted for 39% of failures, add-on or switching therapy for 32%, and uncontrolled HbA1c without intervention for 6%. Cardiorenal comorbidities and SGLT2i-related adverse events increased the risk of failure. Following failure, the use of glucagon-like peptide 1 receptor agonists nearly tripled.

Treatment failure was associated with higher rates of diabetes complications, greater healthcare utilization, and increased costs. These findings highlight the substantial clinical and economic burden of SGLT2i failure and support the need for early combination approaches and tailored treatment strategies.