Effect of sitagliptin on epicardial fat thickness in subjects with type 2 diabetes and obesity: a pilot study

Abstract

The aim of the study was to assess the effect of sitagliptin addition on the epicardial adipose tissue (EAT) thickness in subjects with type 2 diabetes mellitus inadequately controlled on metformin monotherapy. This was a 24-week interventional pilot study in 26 consecutive type 2 diabetic patients, 14 females and 12 males average age of 43.8 ± 9.0 years, with Hemoglobin A1c (HbA1c) ≥ 7% on metformin monotherapy. Subjects who met the inclusion criteria were added on sitagliptin and started on sitagliptin/metformin combination at the dosage of 50 mg/1000 mg twice daily. EAT and visceral and total body fat were measured, respectively, with echocardiography and bioelectrical impedance analysis at baseline and after 24 weeks of sitagliptin/metformin treatment in each subject. HbA1c and plasma lipids were also measured. EAT decreased significantly from 9.98 ± 2.63 to 8.10 ± 2.11 mm, p = 0.001, accounting for a percentage of reduction (∆%) of -15% after 24 weeks of sitagliptin addition, whereas total body fat percentage, visceral fat, and body mass index (BMI), decreased by 8, 12, and 7%, respectively (p = 0.001 for all). After 6 month, EAT ∆% was significantly correlated with ∆% of visceral fat (r = 0.456; p = 0.01), whereas no correlation with either BMI ∆% (r = 0.292; p = 0.147) or HbA1c ∆% was found. The addition of Sitagliptin produced a significant and rapid reduction of EAT, marker of organ-specific visceral fat, in overweight/obese individuals with type 2 diabetes inadequately controlled on metformin monotherapy. EAT as measured with ultrasound can serve as no invasive and accurate marker of visceral fat changes during pharmaceutical interventions targeting the fat.

Sitagliptin in Patients with Non-Alcoholic Steatohepatitis: A Randomized, Placebo-Controlled Trial

“…Since high levels of VAT and low levels of SPAT correlate with insulin resistance, we examined adipose distribution as one of our secondary outcomes. Our results demonstrating no improvement in VAT or SPAT with sitagliptin are in contrast to those by Lima-Martínez et al [42] , who demonstrated decreases in VAT of 12% after 24 wk of sitagliptin therapy. However, the latter trial was open-label without a comparator arm, and utilized a less precise technique (bioimpedance analyzer) compared to MRI to document VAT.…”

Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study

“…Sack et al firstly showed that pioglitazone decreases a genetic expression of proinflammatory and anti-inflammatory cytokines in EF in patients with type 2 diabetes and coronary artery disease [40]. More recently, Lima-Martínez et al reported that the addition of sitagliptin produced a significant and rapid reduction of EFV in overweight/obese patients with type 2 diabetes who were inadequately controlled on metformin monotherapy [41]. Iacobellis et al also has demonstrated that liraglutide, glucagon-like peptide 1 receptor agonist, has a similar effect of reducing the cardiac fat independently of the loss of body weight [42].…”

Clinical importance of epicardial adipose tissue

“…In a longer (26 weeks) randomized controlled trial, exenatide twice daily (versus standard antidiabetic treatment) proved to be effective in reducing both epicardial and liver fat content in obese patients with type 2 diabetes; the effects were mainly weight loss dependent [92]. In another study, sitagliptin, a dipeptidyl-peptidase-4 inhibitor, also decreased the volume of EAT in a 24-week long study with obese type 2 diabetic patients [93]. Clearly, EAT should be considered as a novel therapeutic target, and statins, pioglitazone as well as incretin-based drugs are the best candidates so far [94, 95].…”