Liraglutide reduces cardiac adipose tissue in type 2 diabetes: A secondary analysis of the LIRAFLAME randomized placebo‐controlled trial

Abstract

Aim To test the hypothesis that treatment with liraglutide can reduce cardiac adipose tissue. Materials and methods LIRAFLAME is a randomized placebo‐controlled, double‐blind, parallel clinical study. Participants with type 2 diabetes were randomized to treatment with liraglutide 1.8 mg/d or placebo for 26 weeks. Computed tomography was performed at baseline and at end of treatment to evaluate the cardiac adipose tissue volume, quantified automatically. We report the results of a secondary endpoint evaluating changes in cardiac adipose tissue. Results A total of 102 participants were randomly assigned to liraglutide (n = 51) or placebo (n = 51). At baseline, the mean (SD) cardiac adipose tissue volume was comparable between the liraglutide and the placebo group (232.6 [112.8] vs. 227.0 [103.2] mL; P = 0.80). The mean change in body weight was −3.7 (−4.8, −2.6) kg in the liraglutide and −0.18 (−0.76, 0.40) kg in the placebo group. From baseline to end of treatment the mean cardiac adipose tissue change was −11.5 (95% confidence interval −17.6, −5.4) mL in the liraglutide (P < 0.001) and −0.01 (−5.3, 5.3) mL in the placebo (P = 1.00) groups. The reduction in cardiac adipose tissue was significantly greater in the liraglutide compared to the placebo group (mean difference −11.4 [−19.4, −3.3] mL; P = 0.006), but significance was lost after adjustment for changes in body mass index (P = 0.46). Conclusion Treatment with liraglutide for 26 weeks was associated with a reduction in cardiac adipose tissue compared to placebo. The reduction was not independent of weight loss, suggesting that this is not a drug‐specific effect.

Reduction of cardiac adipose tissue volume with short‐term empagliflozin treatment in patients with type 2 diabetes: A substudy from the SIMPLE randomized clinical trial

“…Using an approach similar to the present trial, Rasmussen et al reported a decrease of 11.4 ml in CAT (approximately 5%) although finding a greater concurrent mean decrease in weight [À3.5 kg 95% CI (À4.8 to À2.3)]. 37 Similarly, longterm exenatide reduced eCAT by 7% in concert with a weight loss of 5%. 38 Although the reduction in accumulated CAT seems almost exclusively dependent on changes in weight, an underlying link has not been fully established.…”

“…A recent study investigated the effects of a 26‐week regimen of the glucagon‐like protein 1 receptor agonist liraglutide in patients with type 2 diabetes. Using an approach similar to the present trial, Rasmussen et al reported a decrease of 11.4 ml in CAT (approximately 5%) although finding a greater concurrent mean decrease in weight [−3.5 kg 95% CI (−4.8 to −2.3)] 37 . Similarly, long‐term exenatide reduced eCAT by 7% in concert with a weight loss of 5% 38 .…”

The potential of glucagon-like peptide-1 receptor agonists in heart failure

“…Accordingly, GLP-1 RA treatment has been shown to directly or indirectly improve cardiometabolic risk factors that characterise diabetes and obesity, and which play central roles in the development or exacerbation of CVD, including HF. These factors include systemic inflammation (Bray et al, 2021;Zobel et al, 2021), hyperglycaemia (Mapanga and Essop, 2016), increased endothelial production of reactive oxygen species (ROS) (Ceriello et al, 2011;Li et al, 2017;Oh and Jun 2017;Lambadiari et al, 2018;Bray et al, 2021) and impaired vasodilation due to low nitrogen oxide bioavailability (Ceriello et al, 2011;Correale et al, 2021). As noted earlier, endothelial dysfunction from increased vessel thickness and stiffness due to for example atherosclerosis may induce or exacerbate cardiac dysfunction.…”

“…As noted earlier, endothelial dysfunction from increased vessel thickness and stiffness due to for example atherosclerosis may induce or exacerbate cardiac dysfunction. GLP-1 RAs have been shown to improve endothelial function (Lambadiari et al, 2018), at least in part due to reduced atherosclerosis owing predominantly to the anti-inflammatory properties of the drug class (Rakipovski et al, 2018;Bray et al, 2021;Zobel et al, 2021) and perhaps to lowering of triglyceride levels (Hermansen et al, 2013;Song et al, 2015).…”

“…People with HFpEF with EAT might benefit specifically from EAT-directed intervention. To that end, GLP-1 RAs might be useful in light of studies demonstrating EAT reductions following treatment with dulaglutide, liraglutide or semaglutide ( Yang et al, 2013 ; Beiroa et al, 2014 ; Iacobellis et al, 2017 ; Iacobellis and Villasante Fricke, 2020 ; Rasmussen et al, 2021 ). In addition, other patient-specific treatment strategies tailoring the use of GLP-1 RAs and other options to the HF phenotype and stage are likely also valuable to study and validate.…”