Clinical Benefit of Switching from Low-Dose to High-Dose Empagliflozin in Patients with Type 2 Diabetes

Takeshi Matsumura; Tomoko Makabe; Seiko Ueda; Yuki Fujimoto; Kayo Sadahiro; Shiori Tsuruyama; Yuma Ookubo; Tatsuya Kondo; Eiichi Araki

doi:10.1007/s13300-022-01296-y

Clinical Benefit of Switching from Low-Dose to High-Dose Empagliflozin in Patients with Type 2 Diabetes

Diabetes Ther. 2022 Sep;13(9):1621-1634. doi: 10.1007/s13300-022-01296-y. Epub 2022 Jul 15.

Authors

Takeshi Matsumura¹, Tomoko Makabe², Seiko Ueda², Yuki Fujimoto³, Kayo Sadahiro², Shiori Tsuruyama², Yuma Ookubo⁴, Tatsuya Kondo⁴, Eiichi Araki⁴

Affiliations

¹ Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. takeshim@gpo.kumamoto-u.ac.jp.
² Department of Pharmacy, Nishinihon Hospital, Kumamoto, Japan.
³ Department of Nursing, Nishinihon Hospital, Kumamoto, Japan.
⁴ Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.

Abstract

Introduction: Sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors ameliorate blood glucose levels in patients with type 2 diabetes mellitus (T2DM) by inhibiting the reabsorption of glucose from the kidneys, thus increasing urinary glucose excretion. Most SGLT2 inhibitors have been reported to exert dose-dependent effects. However, little is known about the benefits of increasing the dose of SGLT2 inhibitors in clinical use. The aim of the present study was to investigate the effect of increasing the dose of the SGLT2 inhibitor empagliflozin in T2DM.

Methods: We collected 52 subjects with T2DM with inadequate glycemic control. The dose of empagliflozin was increased from 10 to 25 mg, taken once daily, and the alterations in glycemic control and several other clinical parameters were evaluated.

Results: The increased dose of empagliflozin significantly ameliorated glycemic control. In addition, body weight (BW), body mass index (BMI), triglyceride (TG), and γ-glutamyltranspeptidase (GGT) were significantly decreased and hematocrit (Hct) was increased. Multivariate logistic regression analyses revealed that baseline diastolic blood pressure (DBP) (odds ratio 1.093, 95% CI 1.019-1.156, P = 0.012) and baseline TG (odds ratio 1.012, 95% CI 1.001-1.023, P = 0.026) were retained as independent predictors for the improvement of hemoglobin A1c (HbA1c) levels. Moreover, multivariate stepwise regression analyses revealed that changes in high-density lipoprotein cholesterol (β - 0.264, 95% CI - 1.217 to 0.000, P = 0.049) and HbA1c (β 0.302, 95% CI 0.077-1.096, P = 0.025) were retained as independent predictors for changes in BMI.

Conclusion: Increasing the dose of empagliflozin significantly ameliorated BW, BMI, GGT, TG, fasting plasma glucose and HbA1c and increased Hct in patients with T2DM. Moreover, baseline DBP and TG were independent predictors for the improvement of HbA1c. These findings may provide useful information when considering increasing the dosage of SGLT2 inhibitors in patients with T2DM who have inadequate glycemic control.

Trial registration: UMIN Clinical Trials Registry (UMIN000041543).

Keywords: Body mass index; Dose-increasing; HbA1c; Sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors; Type 2 diabetes mellitus.