Treatment Selection Patterns and Associated Outcomes for Biguanides and SGLT2 Inhibitors in Type 2 Diabetes: A...

Type 2 diabetes mellitus has multiple treatment options and high healthcare costs. In Japan, DPP-4 inhibitors have been widely used, but since 2022 the pharmacotherapy algorithm has shifted: DPP-4 inhibitors and biguanides for BMI < 25 kg/m $_{}^2$ , and biguanides and SGLT2 inhibitors for BMI $\ge$ 25 kg/m $_{}^2$ . However, real-world factors influencing prescribing decisions between biguanides and SGLT2 inhibitors remain unclear.

This study investigates factors influencing the choice between biguanides and SGLT2 inhibitors in clinical practice. We also compare glycemic efficacy and medication persistence while accounting for baseline characteristics.

This retrospective cohort study used the Millennium Medical Record Database, primarily capturing care from large hospitals. Adults aged $\ge$ 18 years who received a first prescription of a biguanide or a SGLT2 inhibitor between July 2019 and April 2023 were included. Patients were categorized as 1st-line or 2nd-line therapy. Confounding was addressed using coarsened exact matching with classification tree modeling. HbA1c changes were analyzed using mixed models for repeated measures, and persistence using Kaplan-Meier methods.

A total of 1925 patients were included. In the 1st-line cohort (n = 1440), key selection factors were diuretic use, lipid-modifying agents, and baseline HbA1c. At 24 weeks, HbA1c decreased in both groups (biguanide: -1.37 percentage points, 95% CI -1.48 to -1.26; SGLT2 inhibitor: -1.16 percentage points, 95% CI -1.29 to -1.02); the between-group difference was -0.21 percentage points (95% CI -0.38 to -0.04). Persistence at 48 weeks was 47.0% (95% CI 42.7-51.2) for biguanides and 56.2% (95% CI 51.2-61.2) for SGLT2 inhibitors. In the 2nd-line cohort (n = 485), selection factors were baseline HbA1c, BMI, and diuretic use. HbA1c decreased at 24 weeks (biguanide: -2.26 percentage points, 95% CI -2.47 to -2.05; SGLT2 inhibitor: -1.79 percentage points, 95% CI -2.04 to -1.54); the between-group difference was -0.47 percentage points (95% CI -0.80 to -0.15). Persistence at 48 weeks was 51.8% (95% CI 45.2-58.4) for biguanides and 49.4% (95% CI 40.3-58.6) for SGLT2 inhibitors.

In Japanese patients with type 2 diabetes, treatment selection was mainly associated with concomitant cardiovascular medication use. BMI influenced choice, particularly in the 2nd-line setting, but was not the predominant determinant. Biguanides were associated with greater HbA1c reductions. In intention-to-treat analyses, persistence over 48 weeks was higher with SGLT2 inhibitors in the 1st-line cohort, while persistence was comparable in the 2nd-line cohort.