Do reductions in risk of cardiorenal events with SGLT2 inhibitors in type 2 diabetes vary with baseline characteristics? A meta-analysis

Background and objectivesLittle is known about the comparative effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or sodium glucose cotransporter-2 (SGLT2) inhibitors on risk of AKI. This study aimed to compare the effects of these three novel classes of glucose-lowering drugs on AKI risk in patients with or without type 2 diabetes, by network meta-analysis of event-driven cardiovascular or kidney outcome trials.Design, setting, participants, & measurementsWe systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials included patients with type 2 diabetes only, and two trials included patients with or without type 2 diabetes). A network meta-analysis using a frequentist approach was performed to compare the effects of DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors on risk of AKI, and estimate the probability for each intervention as the safest one. The primary analysis included 18 trials with type 2 diabetes only, and a secondary analysis included 20 trials.ResultsIn the 18 trials with a total of 2051 AKI events (range: 1–300) among 156,690 patients with type 2 diabetes only, our network meta-analysis showed that SGLT2 inhibitors were associated with a lower risk of AKI compared with placebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas both DPP-4 inhibitors and GLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than both GLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) and DPP-4 inhibitors (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.86). SGLT2 inhibitors have the highest probability of being the safest intervention (84%). The results were similar in the secondary analysis.ConclusionsCurrent evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.

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Sodium-glucose co-transporter 2 inhibitors (SGLT2i); as a preventive factor of kidney failure in patients with type 2 diabetes; a meta-analysis of randomized controlled trials

Journal of Renal Injury Prevention ◽

10.34172/jrip.2021.35 ◽

2021 ◽

Vol 10 (4) ◽

pp. e35-e35

Author(s):

Dorsa Jahangiri ◽

Udit Narayan Padhi ◽

Henu Kumar Verma ◽

Bhaskar VKS Lakkakula ◽

Rohollah Valizadeh ◽

...

Keyword(s):

Type 2 Diabetes ◽

Renal Replacement Therapy ◽

Replacement Therapy ◽

Meta Analysis ◽

Sglt2 Inhibitors ◽

Renal Outcome ◽

Diabetic Patients ◽

Controlled Trials ◽

Randomized Controlled

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs. SGLT2 inhibitors lower blood glucose levels by decreasing glucose reabsorption in the proximal renal tubule, resulting in increased urinary glucose and sodium excretion. Objective: This study was conducted to investigate the effects of SGLT2i on individual renal outcomes in diabetic patients. Methods: This study was a systematic review and meta-analysis of clinical trials. A comprehensive search of Cochrane Central Register of Controlled Trials was conducted in the Cochrane Library and PubMed, to identify relevant articles focusing on SGLT2i and chronic kidney disease (CKD) in diabetic patients. The most recent article search was conducted on July 12, 2021. Results: Seven randomized controlled trials (RCTs) were included in the meta-analysis. Two trials were comparing dapagliflozin, two comparing empagliflozin, one comparing ertugliflozin, one comparing canagliflozin, and one comparing sotagliflozin. Composite renal outcome and acute kidney injury (AKI) was found in seven and four studies, respectively. Data on end-stage kidney disease (ESKD) and albuminuria or initiation of renal replacement therapy were reported in the two studies. The pooled risk ratio (RR) 95% confidence interval (CI) for the composite renal outcome was 0.54 (0.50–0.59), with 92 % heterogeneity. The pooled RR for AKI was 0.77 (0.66–0.89), with no heterogeneity. A significant lower incidence of albuminuria (RR: 0.69; 95% CI: 0.59–0.81), initiation of renal replacement therapy (RR: 0.71; 95% CI: 0.58–0.87), was observed following the use of SGLT2 inhibitors. Conclusion: Our findings confirm that the SGLT2 inhibitors can reduce the risk of albuminuria, AKI and renal replacement therapy in ESKD patients with T2D (type 2 diabetes). These meta-analyses provide substantial evidence supporting the beneficial effect of SGLT2 inhibitors on reducing CKD events in individuals with T2D.

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