A randomized clinical trial evaluating the effect of empagliflozin on triglycerides in obese adults: Role of visceral fat

Abstract

Background Empagliflozin, a sodium glucose cotransporter 2 inhibitor, is a medication to treat type 2 diabetes. The effect of empagliflozin in persons without diabetes has received less attention. Here we conducted a randomized, double-blind placebo-controlled clinical trial to examine the effect of empagliflozin on plasma triglycerides in obese non-diabetic adults. Methods Participants (n = 35; BMI ≥ 30 kg/m 2 ) underwent body composition assessments using MRI, and were randomly assigned to either placebo or empagliflozin (10 mg/d) for three months. At the baseline and post-treatment visit, after an overnight fast, blood was drawn for biochemical analysis. Participants received [U– 13 C 3 ]glycerol orally followed by multiple blood draws over 3 h to examine glycerol incorporation into triglycerides using NMR spectroscopy. Results The changes in blood triglyceride concentration with empagliflozin therapy related to the mass of baseline visceral adipose tissue (VAT; r = 0.53, p = 0.04). Empagliflozin slightly lowered triglycerides in obese subjects with low VAT, but increased triglycerides in the subjects with high VAT. Consistently, empagliflozin effectively suppressed triglyceride synthesis following [U– 13 C 3 ]glycerol administration in the subjects with low VAT (p < 0.05), but not in the subjects with high VAT. The subjects with high VAT lost body weight after three months of empagliflozin treatment. In all subjects, about 20% of the triglyceride backbone originated from mitochondrial metabolism of glycerol. Conclusions The effect of empagliflozin on triglycerides in obese adults differed depending on VAT. Empagliflozin suppressed triglyceride synthesis in the subjects with low VAT, but tended to increase triglycerides in those with high VAT.

The overall benefits of empagliflozin treatment in adult siblings with glycogen storage disease type Ib: one year experience

“…In our patients, the administration of empagliflozin was associated with marked hypertriglyceridemia, greater in the brother who lost weight during the study. Hypertriglyceridemia is observed in obese subjects with high visceral adipose fat [ 13 ] and may be related to lipolysis and release of glycerol and fatty acids to compensate for glycosuria induced by the SLGT2 inhibitor. This mechanism may be exacerbated in GSD Ib due to intracellular glucose deficiency caused by an absence of glucose-6-phosphate transporter.…”

Comparison of efficacy of anti-diabetics on non-diabetic NAFLD: A network meta-analysis

“…Measurement of the outcome was deemed to be a high risk of bias in three studies ( Cui et al, 2006 ; Yaghoubi et al, 2017 ; Khoo et al, 2019 ). Two studies was found to have a high risk of bias due to selection of the reported result ( Rana et al, 2016 ; Lee et al, 2022 ). Supplementary Figures S1 and Supplementary Figure S2 show the risk-of-bias assessment of the trials included in this study.…”

“…They were all published between 2004 and 2022. Empagliflozin (2 studies) ( Taheri et al, 2020 ; Lee et al, 2022 ), Liraglutide (1 studies) ( Khoo et al, 2019 ), Metformin (9 studies) ( Uygun et al, 2004 ; Garinis et al, 2010 ; Hajiaghamohammadi et al, 2012 ; Sanchez-Munoz et al, 2013 ; Soifer et al, 2015 ; Rana et al, 2016 ; Shahebrahimi et al, 2017 ; Anushiravani et al, 2019 ; Mohammadi et al, 2022 ), Pioglitazone (7 studies) ( Aithal et al, 2008 ; Jin et al, 2010 ; Hajiaghamohammadi et al, 2012 ; Rana et al, 2016 ; Shahebrahimi et al, 2017 ; Yaghoubi et al, 2017 ; Anushiravani et al, 2019 ), Rosiglitzone (1 study) ( Cui et al, 2006 ), Sitagliptin (1 study) ( Doustmohammadian et al, 2022 ), and Vildagliptin (1 study) ( Hussain et al, 2016 ) were interventions involved in our analysis. Eighteen research reported using ALT as an outcome indicator while fifteen studies used AST.…”

The effect of EMPAgliflozin on markers of inflammation in patients with concomitant type 2 diabetes mellitus and Coronary ARtery Disease: the EMPA-CARD randomized controlled trial

“…Empagliflozin modestly increases circulatory free fatty acids and blood ketones (probably by inducing lipolysis) both of which are substrates for formation of MDA and PCG [ 24 , 25 ]. Besides the formation of MDA through the degradation in polyunsaturated lipid triggered by ROS, MDA could also be a product of metabolized prostaglandin-H2 in the prostacyclin synthetase pathway [ 26 ].…”