Effects of glucagon-like peptide-1 receptor agonists on renal function

Table 2 Studies of the effects of liraglutide on renal function

Author	Study details	Main findings
Kim et al[89]	Liraglutide administration in Glp1r(-/-), Nppa(-/-) or wild type mice.	Liraglutide leaded to relaxation of aortic rings through a GLP-1 receptor-dependent but endothelium-independent manner. Liraglutide did not induce ANP secretion and did not result in vasorelaxation or blood pressure reduction in Glp1r(-/-) or Nppa(-/-) mice. Refeeding was associated with an increase in ANP levels in wild-type mice, whereas this effect was not observed in Glp1r(-/-) mice. Liraglutide administration led to increase of urine sodium excretion in wild-type, whereas this effect was abolished in Nppa(-/-) mice. These findings suggest a gut-heart axis, which is both GLP-1 receptor-dependent and ANP-dependent and regulates blood pressure.
Hendarto et al[90]	Liraglutide administration in streptozotocin-induced type 1 diabetes rats. Additionally, incubation of cultured renal mesangial cells with liraglutide for 48 h.	Liraglutide administration in streptozotocin-induced diabetic rats normalized the increased urinary albumin excretion and oxidative stress markers, as well as the expression of NADPH oxidase components, TGF-β1 and fibronectin in renal tissues. The incubation of cultured renal mesangial cells with liraglutide inhibited NADPH-dependent superoxide production in a dose-dependent manner, an effect that was abolished by a protein kinase A inhibitor and an adenylate cyclase inhibitor.
Malm-Erjefalt et al[82]	Administration of radio-labelled liraglutide in seven healthy males.	Liraglutide is metabolized by DPP-IV similarly with the native GLP-1, but at a much slower rate. No intact liraglutide was excreted in urine and feces.
Jacobsen et al[83]	A single dose of liraglutide 0.75 mg was given subcutaneously in 30 subjects (24 with varying degrees of renal impairment and 6 with normal renal function).	No significant effect of reduced creatinine clearance on the pharmacokinetics of liraglutide was observed. No association was found between the degree of renal impairment and the risk of adverse events.
Davidson et al[84]	A meta-analysis of the 6 LEAD (Liraglutide Effect and Action in Diabetes) studies which analysed data from patients with T2DM administered once-daily liraglutide (1.2 or 1.8 mg) or placebo as either monotherapy or in combination with oral antidiabetic drugs for 26 wk.	Mild renal impairment (determined by the Cockcroft-Gault equation) had no significant effect on the efficacy and safety of liraglutide. No significant differences in the rates of nausea, renal injury or minor hypoglycemia were observed between liraglutide and placebo in patients with mild renal impairment. No significant effect of mild renal impairment on HbA1c reduction was observed. However, a trend towards increased nausea was observed with liraglutide in the small number of patients with moderate or severe renal impairment.

GLP-1: Glucagon-like peptide 1; ANP: Atrial natriuretic peptide; TGF-β1: Transforming growth factor beta 1; DPP-IV: Dipeptidyl peptidase IV; T2DM: Type 2 diabetes mellitus; HbA1c: Glycated haemoglobin.