Effects of liraglutide on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria: A sub‐analysis of a randomized, placebo‐controlled, double‐blind, crossover trial

Abstract

We assessed the effects of liraglutide treatment on five cardiovascular risk biomarkers, reflecting different pathophysiology: tumour necrosis factor (TNF)-α; soluble urokinase plasminogen activator receptor (suPAR); mid-regional pro-adrenomedullin (MR-proADM); mid-regional pro-atrial natriuretic peptide (MR-proANP); and copeptin, in people with type 2 diabetes with albuminuria. In a randomized, double-blind, placebo-controlled, crossover trial we enrolled people with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio [UACR] >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m . Participants received liraglutide (1.8 mg/d) and matched placebo for 12 weeks, in random order. The primary endpoint was change in albuminuria; this was a prespecified sub-study. A total of 32 participants were randomized, of whom 27 completed the study. TNF-α level was 12% (95% confidence interval [CI] 3; 20) lower after liraglutide treatment compared with placebo (P = .012); MR-proADM level was 4% (95% CI 0; 8) lower after liraglutide treatment compared with placebo (P = .038), and MR-proANP level was 13% (95% CI 4; 21) lower after liraglutide treatment compared with placebo (P = .006). In the present study, we showed anti-inflammatory effects of liraglutide treatment, reflected in reductions in levels of TNF-α and MR-proADM, while the reduction in MR-proANP levels may represent a clinically relevant benefit with regard to heart failure.

Liraglutide treatment reduced interleukin‐6 in adults with type 1 diabetes but did not improve established autonomic or polyneuropathy

“…Concomitantly with the reduction in IL‐6 were numerical trends present in other cytokines. This is in line with the presence of GLP‐1 receptors demonstrated on monocytes/macrophages and supports the reported 12% reduction of TNF‐α in liraglutide treated patients with type 2 diabetes and microalbuminuria . The shown reduction of microalbuminuria in the liraglutide treated group is in accordance with previous data from the larger outcome studies .…”

“…This is in line with the presence of GLP-1 receptors demonstrated on monocytes/macrophages and supports the reported 12% reduction of TNF-α in liraglutide treated patients with type 2 diabetes and microalbuminuria. 30 The shown reduction of microalbuminuria in the liraglutide treated group is in accordance with previous data from the larger outcome studies. 31,32 In addition, recent findings advocate that the IL-6 pathway seems overactive in 40% of type 1 diabetes patients and that this previously has been implicated in the initiation and progression of microalbuminuria.…”

The emerging role of novel antihyperglycemic agents in the treatment of heart failure and diabetes: A focus on cardiorenal outcomes

“…Consistent with the insulin‐like effect of inducing myocardial glucose uptake, short‐term infusion of GLP‐1 has been shown to improve left ventricular function in humans after coronary reperfusion . A reduction in atherosclerotic burden has also been suggested in humans . GLP‐1 is also expressed on renal endothelium, and GLP‐1 knockout mice develop worse nephropathy compared with wild‐type mice when exposed to hyperglycemia .…”

“…32 A reduction in atherosclerotic burden has also been suggested in humans. 33 GLP-1 is also expressed on renal endothelium, and GLP-1 knockout mice develop worse nephropathy compared with wild-type mice when exposed to hyperglycemia. 34 In addition, GLP-1 has a natriuretic effect, likely due to downregulation of NHE3 activity.…”

SGLT2 Inhibitor and GLP-1 Receptor Agonist Combination Therapy Substantially Improved the Renal Function in a Patient with Type 2 Diabetes: Implications for Additive Renoprotective Effects of the Two Drug Classes

“…Preclinical studies have suggested that GLP-1RAs reduce inflammation and oxidative stress, thereby preventing diabetic nephropathy and acute kidney injury (14)(15)(16)(17). Indeed, the eGFR decline was found to be approximately 2 ml/min/ 1.73 m 2 per year in T2D patients with a baseline eGFR of 30-59 ml/min/1.73 m 2 who were treated by GLP-1RA liraglutide, while it was approximately 4 ml/min/1.73 m 2 per year in a placebo group (estimated trial-group ratio in favor of liraglutide, 1.07; 95% confidence interval, 1.04-1.10; P < 0.001) (6).…”