Dapagliflozin, a feasible alternative to sulphonylureas as an add-on after metformin failure in type 2 diabetes patients

Findings from the BEYOND study revealed that dapagliflozin reduced total body fat (BF) mass, abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) areas and showed better glycemic control than glimepiride at eek 52 among the Korean population with type 2 diabetes (T2D). Dapagliflozin is an SGLT2 (sodium-glucose cotransporter-2) inhibitor that targets the pathophysiological increase in renal glucose reabsorption and shows promising glucose-lowering effects and more favourable pleiotropic effects on the risk of composite renal and cardiovascular outcomes.

In patients with type 2 diabetes, additional antidiabetic agent(s) are generally added for glycemic control after the failure of first-line metformin monotherapy. International treatment guidelines recommend stepwise therapy, and sulphonylureas (SUs) such as glipizide, gliclazide, and glimepiride can be added to metformin as second-line treatment. Sulphonylureas are frequently associated with adverse effects of hypoglycemia and weight gain, but many modern SUs, such as glimepiride, have better safety profiles.

Dapagliflozin is an SGLT2 (sodium-glucose cotransporter-2) inhibitor that targets the pathophysiological increase in renal glucose reabsorption and shows promising glucose-lowering effects and more favourable pleiotropic effects on the risk of composite renal and cardiovascular outcomes.

Against the above background, Hyeong Kyu Park, Soonchunhyang University College of Medicine, Seoul, Korea, and colleagues aimed to evaluate dapagliflozin's effect on body composition such as total body fat mass, abdominal VAT and SAT areas compared with glimepiride in Korean patients with T2D in a 52-week, multicentre, randomized, parallel-group, open-label, Phase IV study (BEYOND study).

The study included 121 patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day). They were randomized in a ratio of 1:1 to receive dapagliflozin 10 mg/day (n=60) or glimepiride 1-2 mg/day (n=61) for 12 months as an addition to metformin therapy. Out of 124 enrolled patients, 106 completed the study. Baseline and end-of-study body composition evaluations included abdominal computed tomography scans and dual-energy X-ray absorptiometry.

The study revealed the following findings:

• Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: −2.59 kg BF mass, −1.94% BF%, −17.55 cm2 VAT area, −18.39 cm2 SAT area, −0.46% glycated haemoglobin, −18.25 mg/dl fasting blood glucose, −3.7 kg weight, −2.21 cm waist circumference, −1.37 kg/m2 body mass index, −6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant.
• Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group.

"The BEYOND study confirms the statistically significant effects of dapagliflozin versus glimepiride as the add-on to metformin in reducing total BF mass and total BF% at week 52 among the Korean population with type 2 diabetes," the researchers wrote.

"Being well tolerated and safe, dapagliflozin is a potentially valuable alternative to sulphonylureas as an add-on after the failure of metformin monotherapy in Korean and other Asian people with T2D," they concluded.

Reference:

Park, Hyeong Kyu, et al. "Effects of Dapagliflozin Compared With Glimepiride On Body Composition in Asian Patients With Type 2 Diabetes Inadequately Controlled With Metformin: the BEYOND Study." Diabetes, Obesity & Metabolism, 2023.