A prospective randomized study comparing effects of empagliflozin to sitagliptin on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes: the ASSET study

Abstract

Background While the cardioprotective benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been established in patients with cardiovascular disease (CVD), their advantages over other anti-diabetic drugs at earlier stages remain unclear. We compared the cardioprotective effects of empagliflozin, an SGLT2 inhibitor, with those of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, focusing on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes mellitus (T2DM) without CVD complications. Methods This was a prospective, randomized, open-label, blinded-endpoint, parallel-group trial that enrolled 44 Japanese patients with T2DM. The patients were randomized for 12-week administration of empagliflozin or sitagliptin. Pericardial fat accumulation and myocardial triglyceride content were evaluated by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Echocardiography, 123I-β-methyl-iodophenyl pentadecanoic acid myocardial scintigraphy, and laboratory tests were performed at baseline and after the 12-week treatment period. Results The patients were middle-aged (50.3 ± 10.7 years, mean ± standard deviation) and overweight (body mass index 29.3 ± 4.9 kg/m2). They had a short diabetes duration (3.5 ± 3.2 years), HbA1c levels of 7.1 ± 0.8%, and preserved cardiac function (ejection fraction 73.8 ± 5.0%) with no vascular complications, except for one baseline case each of diabetic nephropathy and peripheral arterial disease. After the 12-week treatment, no differences from baseline were observed between the two groups regarding changes in pericardial, epicardial, and paracardial fat content; myocardial triglyceride content; cardiac function and mass; and cardiac fatty acid metabolism. However, considering cardiometabolic biomarkers, high-density lipoprotein cholesterol and ketone bodies, including β-hydroxybutyric acid, were significantly increased, whereas uric acid, plasma glucose, plasma insulin, and homeostasis model assessment of insulin resistance were significantly lower in the empagliflozin group than in the sitagliptin group (p < 0.05). Conclusions Although the effects on cardiac fat and function were not statistically different between the two groups, empagliflozin exhibited superior effects on cardiometabolic biomarkers, such as uric acid, high-density lipoprotein cholesterol, ketone bodies, and insulin sensitivity. Therefore, when considering the primary preventive strategies for CVD, early supplementation with SGLT2 inhibitors may be more beneficial than DPP-4 inhibitors, even in patients with early-stage T2DM without current CVD complications. Clinical Trial Registration: UMIN000026340; registered on February 28, 2017. https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000030257

Compounds targeting OSBPL7 increase ABCA1-dependent cholesterol efflux preserving kidney function in two models of kidney disease

“…In a randomized trial of 4300 patients, SGLT2i were unexpectedly found to be efficacious regardless of the presence of diabetes 41 , suggesting that mechanisms of renoprotection other than glucose lowering are involved. In fact, a recent study demonstrated that SGLT2i can increase plasma HDL and may reduce cardiac fat accumulation 42 . This recent emergence of SGLT2i underscores the benefit of targeting multiple CKD driving mechanisms to develop more effective therapies.…”

Effects of sodium‐glucose cotransporter 2 inhibitors on serum uric acid in patients with type 2 diabetes mellitus: A systematic review and network meta‐analysis

“…After further screening, 19 RCTs with 39 arms fulfilled the inclusion criteria and were eventually included in the present study (Figure 1). These RCTs incorporated 4218 adult participants with T2DM, and six SGLT-2 inhibitors were included: empagliflozin, [25][26][27][28] dapagliflozin, [29][30][31][32][33] canagliflozin, 34 ipragliflozin, [35][36][37][38] luseogliflozin [39][40][41] and tofogliflozin. 42,43 In addition, the following baseline characteristics were extracted: registration number, study design, sample size, age, sex, treatment, control, study duration and baseline SUA levels (Table 1).…”

Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

“…The participants in these trials were aged between 18 to 70 years old. Among all included studies, ten trials reported changes in BMI and weight [28,29,[35][36][37][38][39][40][41][42], two studies only reported BMI [43,44], and six studies only reported body weight [45][46][47][48][49][50].…”