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The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Renal Outcomes in Type 2 Diabetes.

ABSTRACT: This review examines the available literature on the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on renal outcomes in type 2 diabetes mellitus. Diabetes is an important cause of end-stage renal disease requiring renal replacement therapy, and diabetic kidney disease is an independent risk factor for cardiovascular disease (CVD). GLP-1RAs are proven to be safe in terms of CVD, and some of them have been shown to have a beneficial effect on cardiovascular outcomes. The effect of GLP-1RAs on hard renal endpoints has yet to be established; to date, there have been no published GLP-1RA clinical trials with primary renal endpoints. In this review, we discuss the evidence for a renal protective role of GLP-1RAs, highlighting the secondary renal outcomes from recent cardiovascular outcome trials of this class of glucose-lowering therapies.

SUBMITTER: Yin WL

PROVIDER: S-EPMC7136364 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Renal Outcomes in Type 2 Diabetes.

Yin Win L WL Bain Steve C SC Min Thinzar T

Diabetes therapy : research, treatment and education of diabetes and related disorders 20200317 4

This review examines the available literature on the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on renal outcomes in type 2 diabetes mellitus. Diabetes is an important cause of end-stage renal disease requiring renal replacement therapy, and diabetic kidney disease is an independent risk factor for cardiovascular disease (CVD). GLP-1RAs are proven to be safe in terms of CVD, and some of them have been shown to have a beneficial effect on cardiovascular outcomes. The effect of ...[more]

PMID: 32185624

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Project description:Background: Cardio-renal profiles are available from cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Methods: A comprehensive systematic review of Embase, Medline, Web of Knowledge, and CENTRAL databases was conducted. Randomized controlled cardiovascular outcome trials of type 2 diabetes mellitus (T2DM) patients administered GLP-1 RAs were included. The following primary outcomes were examined: cardiovascular death, major adverse cardiovascular events (MACE), myocardial infarction, stroke, mortality, heart failure, hypoglycemia, pancreatitis, and thyroid carcinoma. Secondary outcomes included: composite kidney outcome, worsening kidney function, macroalbuminuria, and retinopathy. Results: Seven trials involving 56,004 patients and eight interventions were identified. Albiglutide was associated with fewer MACE and myocardial infarction events compared with lixisenatide. Lixisenatide was related to a greater number of stroke events and cardiovascular deaths compared to once-weekly semaglutide and oral semaglutide, respectively. Improved mortality was associated with oral semaglutide compared with once-weekly semaglutide, albiglutide, dulaglutide, exenatide, or lixisenatide. Risks of heart failure, thyroid carcinoma, and pancreatitis were similar among all the treatments. Weighting of the nine primary outcomes identified oral semaglutide as first among the eight treatments examined. Among three of the secondary outcomes, once-weekly semaglutide ranked first. Better composite kidney outcome was observed with once-weekly semaglutide than with dulaglutide or exenatide; once-weekly semaglutide improved macroalbuminuria compared with exenatide or lixisenatide; and albiglutide, exenatide, and placebo was associated with fewer cases of retinopathy compared with once-weekly semaglutide. Meanwhile, kidney function was less likely to worsen with dulaglutide than with lixisenatide or placebo. Conclusion: Semaglutide should be considered when GLP-1 RAs are indicated for T2DM patients.

Project description:Aims/introductionGlucagon-like peptide-1 receptor agonists (GLP-1Ras) are widely used to treat type 2 diabetes. They not only reduce glucose, but also have a positive effect on weight loss. However, few studies have reported the effect of GLP-1Ras on fat distribution.Materials and methodsPubMed, Cochrane, Embase and ClinicalTrials.gov were searched for randomized controlled trials on GLP-1Ras and type 2 diabetes, published from inception to June 2021. Our main outcomes were the reductions of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Other anthropometric outcomes were also assessed. We used the Cochrane Collaboration tools to assess the risk of bias in the included studies. The quality of the evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation profiler version 3.6. Review Manager 5.4.1 and Stata 16.0 were used for data analysis.ResultsA total of 10 studies involving 541 patients were included. Compared with the control groups, the GLP-1Ras groups showed reductions in VAT (standard mean difference -0.54, 95% confidence interval [CI] -0.92, -0.17, I2 = 79%, P = 0.005) and SAT (standard mean difference -0.44, 95% CI -0.60, -0.27, I2 = 44%, P < 0.00001). In addition, bodyweight (weighted mean difference -3.59, 95% CI -4.30, -2.88, I2 = 0%, P < 0.00001), waist circumference (weighted mean difference -3.09, 95% CI -4.66, -1.52, I2 = 70%, P = 0.0001) and body mass index (weighted mean difference -1.11, 95% CI -1.35, -0.86, I2 = 47%, P < 0.00001) were significantly decreased. According to the Grades of Recommendation, Assessment, Development and Evaluation approach, the level of evidence was low or moderate.ConclusionThis study highlights that GLP-1Ras, especially liraglutide and exenatide, might play an active role in fat distribution in patients with type 2 diabetes. After treatment with GLP-1Ras, both VAT and SAT decreased, and the decrease of VAT was numerically greater than that of SAT.

Dataset Information

The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Renal Outcomes in Type 2 Diabetes.

Publications

The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Renal Outcomes in Type 2 Diabetes.

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