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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:ObjectiveTo assess the effects of finerenone and glucagon-like peptide 1 receptor agonists (GLP1-RA) on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM), and the relative cardiovascular benefits in patients with or without established atherosclerotic cardiovascular disease for different outcomes with these classes of drugs.MethodsWe searched PubMed, the Cochrane Library, and Embase from January 1, 2000, to December 30, 2022, to identify randomized controlled trials. The primary outcomes were the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death (MACE); hospitalization for heart failure (HHF); and a composite of renal outcomes. The results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsIn total, we identified 11 trials and 73,927 participants, 13,847 (18.7%) in finerenone trials and 60,080 (81.3%) in GLP1-RA trials. Finerenone reduced the risk of MACE by 13% (HR, 0.87; 95% CI, 0.79-0.95; P = 0.003), while GLP1-RA reduced the risk in a similar magnitude by 13% (HR, 0.87; 95% CI, 0.83-0.92; P < 0.001). For both drug classes, the effect on lowering the risk of MACE was restricted to approximately 14% in patients with established atherosclerotic cardiovascular disease (HR, 0.86; 95% CI, 0.82-0.90; P < 0.001), whereas no effect was observed in patients without established atherosclerotic cardiovascular disease (HR, 0.93; 95% CI, 0.85-1.02; P = 0.12). GLP1-RA reduced myocardial infarction, stroke and cardiovascular death more than finerenone (which appeared to have no effect). Only finerenone was beneficial for reducing the risk of HHF (HR, 0.78; 95% CI, 0.66-0.92; P = 0.003). Both finerenone (HR, 0.84; 95% CI, 0.77-0.92; P < 0.001) and GLP1-RA (HR, 0.81; 95% CI, 0.76-0.86; P < 0.001) reduced the risk of kidney disease progression, including macroalbuminuria, and finerenone was superior to GLP1-RA in delaying deterioration of kidney function.ConclusionsFinerenone and GLP1-RA lead to a risk reduction in MACE to a similar degree in patients with established atherosclerotic cardiovascular disease. For both drug classes, the effect on lowering the risk of progression of kidney disease was also in a similar magnitude in patients with T2DM, whereas only finerenone had a significant protective effect against HHF. Treatment decisions for patients with T2DM should consider the clinical benefit profiles of each drug.

Project description:BackgroundWe assessed the effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes.MethodsPooled (n=12 637) and by-trial data from SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes; n=3297) and LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; n=9340) were assessed for albuminuria change, annual slope of estimated glomerular filtration rate (eGFR) change, and time to persistent eGFR reduction (30%, 40%, 50%, and 57%) from baseline.ResultsThe median follow-up durations were 2.1 years for SUSTAIN 6 and 3.8 years for LEADER. In the pooled analysis, semaglutide/liraglutide lowered albuminuria from baseline to 2 years after randomization by 24% versus placebo (95% CI, 20%-27%; P<0.001). Significant reductions were also observed in by-trial data analyses (P<0.001 for all), the largest being with semaglutide 1.0 mg (33% [95% CI, 24%-40%]; P<0.001) at 2 years. With semaglutide 1.0 mg and liraglutide, eGFR slope decline was significantly slowed by 0.87 and 0.26 mL/min/1.73 m2/y (P<0.0001 and P<0.001), respectively, versus placebo. Effects appeared larger in patients with baseline eGFR <60 versus ≥60 mL/min/1.73 m2 (Pinteraction=0.06 and 0.008 for semaglutide 1.0 mg and liraglutide, respectively). Semaglutide/liraglutide significantly lowered risk of persistent 40% and 50% eGFR reductions versus placebo (hazard ratio [HR], 0.86 [95% CI, 0.75-0.99]; P=0.039 and HR, 0.80 [95% CI, 0.66-0.97]; P=0.023, respectively). Similar, nonsignificant, directional results were observed for 30% and 57% eGFR reductions (HR, 0.92 [95% CI, 0.84-1.02]; P=0.10 and HR, 0.89 [95% CI, 0.69-1.13]; P=0.34). In patients with baseline eGFR 30 to <60 mL/min/1.73 m2, the likelihood of persistent reduction for all thresholds was increased, ranging from HR 0.71 for 30% reduction (95% CI, 0.59-0.85; P=0.0003, Pinteraction=0.017) to 0.54 for 57% reduction (95% CI, 0.36-0.81; P=0.003, Pinteraction=0.035).ConclusionsIn patients with type 2 diabetes, semaglutide/liraglutide offered kidney-protective effects, which appeared more pronounced in patients with preexisting chronic kidney disease.

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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