Comparative Clinical Analysis of DPP-4 inhibitors and SGLT2 Inhibitors: A Real-World Switch Study

Dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose co-transporter 2 (SGLT2) inhibitors are contemporary oral antidiabetic medications, each offering distinct advantages and challenges. Understanding their comparative effectiveness in real-world settings is crucial for optimizing treatment strategies.

We retrospectively analyzed adults with type 2 diabetes mellitus who switched between DPP-4 inhibitors and SGLT2 inhibitors from December 1, 2014, to November 26, 2023, using a clinical data warehouse. All participants had baseline glycosylated hemoglobin (HbA1c) levels between 6.5% and 10.0% and were receiving metformin. To reduce baseline imbalance in HbA1c and fasting plasma glucose (FPG), we excluded patients with an estimated glomerular filtration rate <45 mL/min/1.73 m² and performed 1:1 propensity-score matching on baseline levels of HbA1c and FPG. The matched cohort included 168 patients (84 per group). The primary outcome was the between-group difference in change in HbA1c over 3 months. Secondary outcomes were changes in FPG, body mass index (BMI), liver enzymes, and renal function.

Switching to DPP-4 inhibitors was associated with a greater reduction in HbA1c (β, -0.26; 95% confidence interval [CI], -0.51 to -0.01; P<0.001). In contrast, switching to SGLT2 inhibitors led to significant improvements in FPG (β, 10.50; 95% CI, 0.22 to 20.78; P<0.001) and liver enzyme levels. Older patients and those with a lower BMI, higher baseline HbA1c, or chronic kidney disease derived greater benefit from switching to DPP-4 inhibitors.

Transitioning to DPP-4 inhibitors reduced HbA1c levels significantly, whereas switching to SGLT2 inhibitors improved FPG and liver-related metabolic parameters.