Dataset Information

Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney Injury.

ABSTRACT:

Background and objectives

Little 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, & measurements

We 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.

Results

In 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.

Conclusions

Current evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.

SUBMITTER: Zhao M

PROVIDER: S-EPMC7792639 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Acute kidney injury (AKI) is associated with several adverse outcomes, including new or progressive chronic kidney disease, end-stage kidney disease, and mortality. Epidemiological studies have reported an association between AKI and dementia as a long-term adverse outcome. This meta-analysis was aimed to understand the association between AKI and dementia risk. A literature search was performed in MEDLINE and Embase databases, from inception to July 2021, to identify epidemiological studies reporting the association between AKI and dementia risk. Title and abstract followed by the full-text of retrieved articles were screened, data were extracted, and quality was assessed, using the Newcastle-Ottawa scale by two investigators independently. The primary outcome was to compute the pooled risk of dementia in AKI patients. Subgroup analysis was also performed based on age and co-morbidities. Certainty of evidence was assessed using the GRADE approach. Statistical analysis was performed using Review Manager 5.4 software. Four studies (cohort (n = 3) and case-control (n = 1)) with a total of 429,211 patients, of which 211,749 had AKI, were identified. The mean age of the patients and the follow-up period were 64.15 ± 16.09 years and 8.9 years, respectively. Included studies were of moderate to high quality. The pooled estimate revealed a significantly higher risk of dementia in AKI patients with an overall relative risk/risk ratio (RR) of 1.92 (95% CI: 1.52-2.43), p ≤ 0.00001. Dementia risk increases by 10% with one year increase in age with an RR of 1.10 (95% CI: 1.09-1.11), p < 0.00001. Subgroup analysis based on stroke as a co-morbid condition also revealed significantly higher dementia risk in AKI patients (RR 2.30 (95% CI: 1.62-3.28), p = 0.009). All-cause mortality risk was also significantly higher in AKI patients with dementia with a pooled RR of 2.11 (95% CI: 1.20-3.70), p = 0.009. The strength of the evidence was of very low certainty as per the GRADE assessment. Patients with AKI have a higher risk of dementia. Further large epidemiological studies are needed to confirm the mechanistic association.