Discrepancies in Dapagliflozin Response in Terms of Glycemic Control and Body Weight Reduction

Abstract

Backgruound: Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduces hyperglycemia and obesity by inhibiting renal glucose reabsorption. This post hoc study evaluated clinical factors influencing patient response to dapagliflozin.

Methods: The analysis focused on patients treated with dapagliflozin (10 mg/day for 52 weeks) within the randomized, double-blind, parallel-group BEYOND trial. Adequate glycemic control (GC) was defined as a reduction in glycated hemoglobin (HbA1c) of ≥ 1.0% or the achievement of an HbA1c level <7.0% at week 52. Significant weight loss (WL) referred to a reduction in body weight of ≥3.0% at week 52. Participants were classified into four groups based on their GC and WL responses: GC+/WL+, GC+/WL-, GC-/WL+, and GC-/WL-.

Results: Among dapagliflozin recipients (n=56), at 52 weeks, HbA1c had decreased by 1.0%±0.8% from baseline, while body weight had declined by 2.4±3.1 kg. Overall, 69.6% of participants achieved GC+, and 57.1% achieved WL+. Male sex and shorter diabetes duration were significantly associated with achieving GC+. Conversely, higher estimated glomerular filtration rate was significantly linked to WL+. The only factor significantly associated with both GC+ and WL+ was shorter diabetes duration (odds ratio, 0.81; 95% confidence interval, 0.68 to 0.97; P=0.023). The GC+ and WL+ groups exhibited favorable responses beginning soon after dapagliflozin therapy was initiated. Furthermore, HbA1c decline was more strongly associated with reduction in visceral fat than with WL.

Conclusion: A short duration of diabetes and early response to treatment appear to represent key factors in maximizing the benefits of dapagliflozin for blood glucose and weight management.

Keywords: Dapagliflozin; Diabetes mellitus, type 2; Effectiveness; Sodium-glucose transporter 2 inhibitors.

Fig. 1.

Scatter plot illustrating the correlation between absolute percentage change in glycated hemoglobin (HbA1c) level and percentage change in body weight (BW). Blue dots indicate patients who achieved both adequate glycemic control (GC) and significant weight loss (WL). Green dots denote patients who achieved adequate GC without significant WL. Red dots represent patients who have achieved adequate WL without GC. Black dots indicate patients who did not achieved adequate GC or WL.