|Angiotensin receptor blockers for prevention of new-onset type 2 diabetes: a meta-analysis of 59,862 patients
|Geng DF, Jin DM, Wu W, Xu Y, Wang JF
The review found that angiotensin receptor blockers reduced the incidence of new-onset diabetes in patients with cardiovascular disease or risk factors. Despite some limitations in the review methodology and the evidence base, these conclusions appear reliable.
To assess the effect of angiotensin receptor blockers on the development of new-onset type 2 diabetes.
PubMed and EMBASE (from inception), BIOSIS Previews (from 1997) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to 2010. Search terms used were not reported. The reviewers searched the 2003 to 2009 conference proceedings of five diabetes and cardiology professional bodies, and checked the reference lists of articles retrieved for additional studies. It was unclear whether the search was restricted by language.
Eligible studies were randomised controlled trials (RCTs) of at least one year's duration that compared an angiotensin receptor blocker to a different type of drug or placebo in participants with at least one cardiovascular risk factor or cardiovascular disease. Studies were required to report the incidence of new-onset type 2 diabetes. Studies of angiotensin receptor blockers versus angiotension converting enzyme inhibitors were excluded.
In the included studies, 35% to 80% of participants were male, age ranged from 64 to 76 years and body mass index ranged from 25 to 30 kilograms per square metre (where reported). Participants had a variety of cardiovascular disorders or risk factors, the most common being hypertension. The review focused on the 75% of participants who were non-diabetic, among whom 90% were described as Western and 10% were Japanese. Angiotensin receptor blockers (candesartan, telmisartan, valsartan and losartan) were compared with amlodipine, atenolol, placebo or non-angiotensin receptor blockers. In most studies new-onset diabetes was defined using 1999 World Health Organisation criteria. Diabetes was not a primary outcome in any of the included trials, and was not confirmed by systematic glucose measurement. The mean or median duration of study follow-up ranged from 2.5 to five years. The authors did not state how many reviewers performed study selection.
Assessment of study quality
The following aspects of study quality were assessed: randomisation, allocation concealment, blinding, use of intention-to-treat analysis, completeness of follow-up and baseline comparability of study arms. The assessment was conducted independently by two reviewers, with discrepancies resolved by consensus or by a third reviewer.
Data to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for new-onset diabetes were extracted for each study.
Two reviewers independently extracted data. Discrepancies were resolved by consensus or by a third reviewer.
Methods of synthesis
Data were combined to calculate pooled odds ratios and 95% confidence intervals using a random-effects model. Heterogeneity was assessed with Χ² and Ι². Subgroup analysis was conducted to assess the effects of differences in type of angiotensin receptor blocker, population, control intervention, primary disease and achieved blood pressure level.
Results of the review
Eleven RCTs were included in the review (79,733 participants, 59,872 of whom were non-diabetic; overall range 2,028 to 20,332). Ten used a computer-generated randomisation sequence; at least seven used independent or remote allocation; all were double-blinded or used blinded outcomes assessment, described withdrawals and used intention-to-treat analysis; none had complete follow-up. Confounding factors were well balanced between the arms at baseline.
The rate of new-onset diabetes was significantly lower in the angiotensin receptor blocker group (OR 0.79, 95% CI 0.74 to 0.84, 11 RCTs, Ι²=12.7%). In subgroup analyses, a significant benefit of angiotensin receptor blockers was found for different types of angiotensin receptor blocker (candesartan, telmisartan, valsartan and losartan), control intervention (placebo, beta-blocker, calcium channel blocker, non-angiotensin receptor blocker), population (Western or Japanese), primary disease (hypertension, heart failure, cerebrovascular disease, impaired glucose tolerance with cardiovascular disease or risk factors) and achieved blood pressure level.
Angiotensin receptor blockers reduced the incidence of new-onset diabetes.
The objectives and inclusion criteria of the review were clear and relevant sources were searched for published and unpublished studies. Search terms were not reported, so the quality of the search was unclear. It was unclear whether the search was restricted by language, in which case some studies may have been missed, and it appeared that the risk of publication bias was not assessed. It was unclear whether study selection was undertaken with sufficient efforts to minimise error and bias. Data extraction was done by two independent reviewers. Appropriate methods were used to assess study quality, statistically combine the studies and investigate differences between them.
Study quality appeared satisfactory, statistical heterogeneity was low and the review findings were consistent across subgroups. The authors noted that the review was limited by differences between the primary studies in study duration and in definition of diabetes, and by lack of trials in which diabetes was the primary outcome or in which diabetes was confirmed by systematic glucose measurement. Despite these limitations, the authors' conclusions reflect the evidence presented and appear reliable.
Implications of the review for practice and research
Practice: The authors stated that use of angiotensin receptor blockers should be considered for prevention of new-onset diabetes in patients at high risk.
Research: The authors did not state any implications for research.
Geng DF, Jin DM, Wu W, Xu Y, Wang JF. Angiotensin receptor blockers for prevention of new-onset type 2 diabetes: a meta-analysis of 59,862 patients. International Journal of Cardiology 2012; 155(2): 236-242
Subject indexing assigned by NLM
Angiotensin Receptor Antagonists /therapeutic use; Diabetes Mellitus, Type 2 /prevention & control; Glucose Intolerance /drug therapy; Humans; Hypertension /drug therapy; Randomized Controlled Trials as Topic
Database entry date
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.