Long-Term Effectiveness of Quadruple Combination Therapy with Empagliflozin Versus Basal Long-Acting Insulin Therapy in Patients with Type 2 Diabetes: 3-Year Retrospective Observational Study

Abstract

Introduction: Effective blood glucose control remains a constant problem in patients with type 2 diabetes (T2D), even if they are being properly treated with one or more currently available drugs. The present study was designed as a 3-year retrospective observational study to determine whether the use of either empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, or insulin would provide any improvement in the control of the blood glucose levels in patients with T2D who were already being treated with a cocktail of three different oral antidiabetic drugs.

Methods: Adult patients with T2D were enrolled in this study if they exhibited suboptimal glycemic control (HbA1c 7.5-12.0%) despite being continuously treated for at least 3 months with metformin, dipeptidyl-peptidase 4 inhibitor, and glimepiride. Empagliflozin (25 mg/day, n = 154) or basal long-acting insulin (n = 147) was added as a fourth medication to the existing drug regimen. The major outcomes that were monitored in this study included the measurement of HbA1c, fasting plasma glucose (FPG), and general cardiometabolic and blood markers.

Results: After the addition of empagliflozin or basal insulin to the existing oral anti-diabetic agent (OAD) regimen, the baseline levels of HbA1c were reduced after month 36 in both the empagliflozin (8.9 ± 1.0% to 7.4 ± 0.8%, P < 0.01) and insulin (9.0 ± 1.4% to 8.0 ± .1.4%, P < 0.05) groups. The HbA1c reduction was higher in the empagliflozin group to the end of the 36-month study period (7.4 ± 0.8% vs. 8.0 ± 1.4%, empagliflozin vs. insulin, P < 0.05). FPG showed a similar trend in the early period but it was not maintained at the end of study. Body weight decreased (P < 0.01) from baseline (70.4 ± 12.3 kg) to month 36 (65.6 ± 11.4 kg) in the empagliflozin group but not the insulin group. At 36 months, the body weight in the empagliflozin group (65.6 ± 11.4 kg) was significantly lower (P < 0.01) than that in the insulin treatment group (70.0 ± 10.9 kg).

Conclusion: Empagliflozin was shown to perform as well as better than insulin when used as part of a quadruple drug regimen for regulating blood glucose levels in suboptimally controlled patients with T2D.

Clinical trial number: NCT05103306 (ClinicalTrials.gov).

Keywords: Durability; Empagliflozin; Quadruple combination therapy; SGLT2 inhibitor; Type 2 diabetes mellitus.