Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes: A network and cumulative meta-analysis of randomized controlled trials

Huilin Tang, Dandan Li, Jingjing Zhang, Yufeng Li, Tiansheng Wang, Suodi Zhai, Yiqing Song

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Aim: To compare the associations of individual sodium-glucose co-transporter-2 (SGLT2) inhibitors with adverse renal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods: PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched for studies published up to May 24, 2016, without language or date restrictions. Randomized trials that reported at least 1 renal-related adverse outcome in patients with T2DM treated with SGLT2 inhibitors were included. Pairwise and network meta-analyses were carried out to calculate the odds ratios (ORs) with 95% confidence intervals (CIs), and a cumulative meta-analysis was performed to assess the robustness of evidence. Results: In total, we extracted 1334 composite renal events among 39 741 patients from 58 trials, and 511 acute renal impairment/failure events among 36 716 patients from 53 trials. Dapagliflozin was significantly associated with a greater risk of composite renal events than placebo (OR 1.64, 95% CI 1.26-2.13). Empagliflozin seemed to confer a lower risk than placebo (OR 0.63, 95% CI 0.54-0.72), canagliflozin (OR 0.48, 95% CI 0.29-0.82) and dapagliflozin (OR 0.38, 95% CI 0.28-0.51). With regard to acute renal impairment/failure, only empagliflozin was significantly associated with a lower risk than placebo (OR 0.72, 95% CI 0.60-0.86). The cumulative meta-analysis indicated the robustness of our significant findings. Conclusions: The present meta-analysis indicated that dapagliflozin may increase the risk of adverse renal events, while empagliflozin may have a protective effect among patients with T2DM. Further data from large well-conducted randomized controlled trials and a real-world setting are warranted.

Original languageEnglish (US)
Pages (from-to)1106-1115
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2017

Fingerprint

Sodium-Glucose Transporter 2
Symporters
Type 2 Diabetes Mellitus
Randomized Controlled Trials
Odds Ratio
Confidence Intervals
Kidney
Meta-Analysis
Placebos
Acute Kidney Injury
PubMed
Network Meta-Analysis
Language

Keywords

  • meta-analysis
  • renal outcomes
  • SGLT2 inhibitor
  • type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes : A network and cumulative meta-analysis of randomized controlled trials. / Tang, Huilin; Li, Dandan; Zhang, Jingjing; Li, Yufeng; Wang, Tiansheng; Zhai, Suodi; Song, Yiqing.

In: Diabetes, Obesity and Metabolism, Vol. 19, No. 8, 01.08.2017, p. 1106-1115.

Research output: Contribution to journalArticle

@article{90ff716effc34b77ab6f92d0a5d79f02,
title = "Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes: A network and cumulative meta-analysis of randomized controlled trials",
abstract = "Aim: To compare the associations of individual sodium-glucose co-transporter-2 (SGLT2) inhibitors with adverse renal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods: PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched for studies published up to May 24, 2016, without language or date restrictions. Randomized trials that reported at least 1 renal-related adverse outcome in patients with T2DM treated with SGLT2 inhibitors were included. Pairwise and network meta-analyses were carried out to calculate the odds ratios (ORs) with 95{\%} confidence intervals (CIs), and a cumulative meta-analysis was performed to assess the robustness of evidence. Results: In total, we extracted 1334 composite renal events among 39 741 patients from 58 trials, and 511 acute renal impairment/failure events among 36 716 patients from 53 trials. Dapagliflozin was significantly associated with a greater risk of composite renal events than placebo (OR 1.64, 95{\%} CI 1.26-2.13). Empagliflozin seemed to confer a lower risk than placebo (OR 0.63, 95{\%} CI 0.54-0.72), canagliflozin (OR 0.48, 95{\%} CI 0.29-0.82) and dapagliflozin (OR 0.38, 95{\%} CI 0.28-0.51). With regard to acute renal impairment/failure, only empagliflozin was significantly associated with a lower risk than placebo (OR 0.72, 95{\%} CI 0.60-0.86). The cumulative meta-analysis indicated the robustness of our significant findings. Conclusions: The present meta-analysis indicated that dapagliflozin may increase the risk of adverse renal events, while empagliflozin may have a protective effect among patients with T2DM. Further data from large well-conducted randomized controlled trials and a real-world setting are warranted.",
keywords = "meta-analysis, renal outcomes, SGLT2 inhibitor, type 2 diabetes",
author = "Huilin Tang and Dandan Li and Jingjing Zhang and Yufeng Li and Tiansheng Wang and Suodi Zhai and Yiqing Song",
year = "2017",
month = "8",
day = "1",
doi = "10.1111/dom.12917",
language = "English (US)",
volume = "19",
pages = "1106--1115",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes

T2 - A network and cumulative meta-analysis of randomized controlled trials

AU - Tang, Huilin

AU - Li, Dandan

AU - Zhang, Jingjing

AU - Li, Yufeng

AU - Wang, Tiansheng

AU - Zhai, Suodi

AU - Song, Yiqing

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Aim: To compare the associations of individual sodium-glucose co-transporter-2 (SGLT2) inhibitors with adverse renal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods: PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched for studies published up to May 24, 2016, without language or date restrictions. Randomized trials that reported at least 1 renal-related adverse outcome in patients with T2DM treated with SGLT2 inhibitors were included. Pairwise and network meta-analyses were carried out to calculate the odds ratios (ORs) with 95% confidence intervals (CIs), and a cumulative meta-analysis was performed to assess the robustness of evidence. Results: In total, we extracted 1334 composite renal events among 39 741 patients from 58 trials, and 511 acute renal impairment/failure events among 36 716 patients from 53 trials. Dapagliflozin was significantly associated with a greater risk of composite renal events than placebo (OR 1.64, 95% CI 1.26-2.13). Empagliflozin seemed to confer a lower risk than placebo (OR 0.63, 95% CI 0.54-0.72), canagliflozin (OR 0.48, 95% CI 0.29-0.82) and dapagliflozin (OR 0.38, 95% CI 0.28-0.51). With regard to acute renal impairment/failure, only empagliflozin was significantly associated with a lower risk than placebo (OR 0.72, 95% CI 0.60-0.86). The cumulative meta-analysis indicated the robustness of our significant findings. Conclusions: The present meta-analysis indicated that dapagliflozin may increase the risk of adverse renal events, while empagliflozin may have a protective effect among patients with T2DM. Further data from large well-conducted randomized controlled trials and a real-world setting are warranted.

AB - Aim: To compare the associations of individual sodium-glucose co-transporter-2 (SGLT2) inhibitors with adverse renal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods: PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched for studies published up to May 24, 2016, without language or date restrictions. Randomized trials that reported at least 1 renal-related adverse outcome in patients with T2DM treated with SGLT2 inhibitors were included. Pairwise and network meta-analyses were carried out to calculate the odds ratios (ORs) with 95% confidence intervals (CIs), and a cumulative meta-analysis was performed to assess the robustness of evidence. Results: In total, we extracted 1334 composite renal events among 39 741 patients from 58 trials, and 511 acute renal impairment/failure events among 36 716 patients from 53 trials. Dapagliflozin was significantly associated with a greater risk of composite renal events than placebo (OR 1.64, 95% CI 1.26-2.13). Empagliflozin seemed to confer a lower risk than placebo (OR 0.63, 95% CI 0.54-0.72), canagliflozin (OR 0.48, 95% CI 0.29-0.82) and dapagliflozin (OR 0.38, 95% CI 0.28-0.51). With regard to acute renal impairment/failure, only empagliflozin was significantly associated with a lower risk than placebo (OR 0.72, 95% CI 0.60-0.86). The cumulative meta-analysis indicated the robustness of our significant findings. Conclusions: The present meta-analysis indicated that dapagliflozin may increase the risk of adverse renal events, while empagliflozin may have a protective effect among patients with T2DM. Further data from large well-conducted randomized controlled trials and a real-world setting are warranted.

KW - meta-analysis

KW - renal outcomes

KW - SGLT2 inhibitor

KW - type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85017337183&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017337183&partnerID=8YFLogxK

U2 - 10.1111/dom.12917

DO - 10.1111/dom.12917

M3 - Article

C2 - 28240446

AN - SCOPUS:85017337183

VL - 19

SP - 1106

EP - 1115

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 8

ER -