Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies - PubMed (original) (raw)

Review

doi: 10.1136/bmj.i610.

Sheyu Li 2, Ke Deng 3, Jiali Liu 1, Per Olav Vandvik 4, Pujing Zhao 1, Longhao Zhang 1, Jiantong Shen 1, Malgorzata M Bala 5, Zahra N Sohani 6, Evelyn Wong 7, Jason W Busse 8, Shanil Ebrahim 9, German Malaga 10, Lorena P Rios 11, Yingqiang Wang 12, Qunfei Chen 13, Gordon H Guyatt 14, Xin Sun 15

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Review

Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies

Ling Li et al. BMJ. 2016.

Abstract

Objectives: To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes.

Design: Systematic review and meta-analysis of randomised and observational studies.

Data sources: Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts.

Eligibility criteria: Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure.

Data collection and analysis: Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach.

Results: Eligible studies included 43 trials (n=68,775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1,777,358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15,701 v 33/12,591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18,554 v 552/18,474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use.

Conclusions: The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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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: support from the National Natural Science Foundation of China, “Thousand Youth Talents Plan” of China and Sichuan Province, and Young Investigator Award of Sichuan University 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 Flowchart of article selection

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Fig 2 Risk of heart failure in patients with type 2 diabetes who received DPP-4 inhibitors versus control from randomised controlled trials

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Fig 3 Risk of hospital admission for heart failure in patients with type 2 diabetes who received DPP-4 inhibitors versus control from randomised controlled trials

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Fig 4 Risk of hospital admission for heart failure in patients with type 2 diabetes who received DPP-4 inhibitors versus control based on adjusted data from observational studies. SE=standard error; IV=inverse variance

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References

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