Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis
Jiali Liu,Ling Li,Ke Deng,Chang Xu,Jason W. Busse,Per Olav Vandvik,Sheyu Li,Gordon H. Guyatt,Xin Sun +8 more
TLDR
Current evidence does not support the suggestion that incretin based treatment increases all cause mortality in patients with type 2 diabetes and suggested the possibility of a mortality benefit with GLP-1 agonists but not DPP-4 inhibitors.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, I 2 =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.read more
Citations
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Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis.
Sean L. Zheng,Sean L. Zheng,Alistair J. Roddick,Rochan Aghar-Jaffar,Rochan Aghar-Jaffar,Matthew J. Shun-Shin,Darrel P. Francis,Nick Oliver,Nick Oliver,Karim Meeran,Karim Meeran +10 more
TL;DR: A network meta-analysis of 236 trials randomizing 176 310 participants found the use of SGLT-2 inhibitors or GLP-1 agonists was associated with lower mortality than DPP-4 inhibitors or placebo or no treatment.
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John Atherton,Andrew Sindone,Carmine G. De Pasquale,Andrea Driscoll,Peter S. Macdonald,Ingrid Hopper,Peter M. Kistler,Tom Briffa,James Wong,Walter P. Abhayaratna,Liza Thomas,Ralph Audehm,Phillip J. Newton,Joan O'Loughlin,Marie Branagan,Cia Connell +15 more
TL;DR: This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
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