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Review
. 2017 Jun 8:357:j2499.
doi: 10.1136/bmj.j2499.

Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis

Jiali Liu  1 , Ling Li  1 , Ke Deng  1 , Chang Xu  1 , Jason W Busse  2   3   4 , Per Olav Vandvik  5   6 , Sheyu Li  7 , Gordon H Guyatt  2   8 , Xin Sun  9
Affiliations
Review

Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis

Jiali Liu et al. BMJ. .

Abstract

Objective To assess the impact of incretin based treatment on all cause mortality in patients with type 2 diabetes.Design Systematic review and meta-analysis of randomised trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov.Eligibility criteria Randomised controlled trials that compared glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors with placebo or active anti-diabetic drugs in patients with type 2 diabetes.Data collection and analysis Paired reviewers independently screened citations, assessed risk of bias of included studies, and extracted data. Peto's method was used as the primary approach to pool effect estimates from trials, sensitivity analyses were carried out with other statistical approaches, and meta-regression was applied for six prespecified hypotheses to explore heterogeneity. The GRADE approach was used to rate the quality of evidence.Results 189 randomised controlled trials (n=155 145) were included, all of which were at low to moderate risk of bias; 77 reported no events of death and 112 reported 3888 deaths among 151 614 patients. Meta-analysis of 189 trials showed no difference in all cause mortality between incretin drugs versus control (1925/84 136 v 1963/67 478; odds ratio 0.96, 95% confidence interval 0.90 to 1.02, I2=0%; risk difference 3 fewer events (95% confidence interval 7 fewer to 1 more) per 1000 patients over five years; moderate quality evidence). Results suggested the possibility of a mortality benefit with GLP-1 agonists but not DPP-4 inhibitors, but the subgroup hypothesis had low credibility. Sensitivity analyses showed no important differences in the estimates of effects.Conclusions Current evidence does not support the suggestion that incretin based treatment increases all cause mortality in patients with type 2 diabetes. Further studies are warranted to examine if the effect differs between GLP-1 agonists versus DPP-4 inhibitors.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Flow chart of selection of studies on incretin based treatments and mortality in patients with type 2 diabetes
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Fig 2 All cause mortality in patients with type 2 diabetes receiving incretin based treatment versus control in randomised controlled trials
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Fig 3 Funnel plot of mortality in patients with type 2 diabetes receiving incretin based treatment versus control in randomised controlled trials
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Fig 4 All cause mortality in patients with type 2 diabetes receiving incretin based treatment versus placebo in large cardiovascular outcomes trials
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Fig 5 Composite cardiovascular events (death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke) in patients with type 2 diabetes receiving incretin based treatment versus placebo in large cardiovascular outcomes trials
See this image and copyright information in PMC

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