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School of Pharmacy


Pharmaceutical Systems and Policy


Introduction Cardiovascular diseases are the leading cause of morbidity and mortality among individuals with diabetes. Despite the beneficial effects of antidiabetic drugs (ADDs) in terms of lowering haemoglobin A1c, several ADDs have been shown to increase the risk of cardiovascular events. Given the high prevalence of cardiovascular disease among individuals with diabetes, it is important to weigh the benefits of ADDs against their cardiovascular safety. Therefore, the objective of the current study is to conduct a systematic review with network meta-analysis to compare the effects of different oral pharmacological classes of ADDs on cardiovascular safety.

Methods and analysis Randomised clinical trials (RCTs) and observational studies published in English up to 31 January 2017, and which include direct and/or indirect evidence, will be included. Studies will be retrieved by searching four electronic databases and cross-referencing. Dual selection and abstraction of data will occur. The primary outcome will be cardiovascular mortality. Secondary outcomes will include all-cause mortality, new event of acute myocardial infarction, stroke (haemorrhagic and ischaemic), hospitalisation for acute coronary syndrome and urgent revascularisation procedures. Risk of bias will be assessed using the Cochrane Risk of Bias assessment instrument for RCTs and the Strengthening the Reporting of Observational Studies in Epidemiology instrument for observational studies. Network meta-analysis will be performed using multivariate random-effects meta-regression models. The surface under the cumulative ranking curve will be used to provide a hierarchy of ADDs that increase cardiovascular mortality.

Dissemination The results of this study will be presented at a professional conference and submitted to a peer-reviewed journal.

PROSPERO registration number CRD42017051220.

Source Citation

Goyat R, Thornton JD, Tan X, et alCardiovascular mortality and oral antidiabetic drugs: protocol for a systematic review and network meta-analysisBMJ Open 2017;7:e017644. doi: 10.1136/bmjopen-2017-017644


© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

This article was supported by the WVU Libraries' Open Access Author Fund.


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