The risk of heart failure associated with the use of noninsulin blood glucose-lowering drugs: systematic review and meta-analysis of published observational studies

BMC Cardiovascular Disorders

Susana Perez-Gutthann¹  Silvana Romio²  Lorna Hazell⁴  Brian Calingaert³  Nuria Riera-Guardia¹  Manel Pladevall¹  Andrea V Margulis¹  Cristina Varas-Lorenzo¹ 

[1] RTI Health Solutions, Trav. Gracia 56 Atico 1 08006, Barcelona, Spain;Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, Laboratory of Healthcare Research and Pharmacoepidemiology, University Milano-Bicocca, Milan, Italy;RTI Health Solutions, 200 Park Offices Drive, Research Triangle Park, NC 27709, USA;Drug Safety Research Unit, Bursledon Hall, Blundell Lane, Southampton, S031 1AA, UK

关键词: Observational studies;    Pharmacoepidemiology;    Cardiovascular safety;    Meta-analysis;    Heart failure risk;    Type 2 diabetes mellitus;    Blood glucose-lowering drugs;   

Others  :  1088443
DOI  :  10.1186/1471-2261-14-129

 received in 2014-07-03, accepted in 2014-09-22,  发布年份 2014

【 摘 要 】

Background

Patients with type 2 diabetes mellitus (T2DM) are at high risk of heart failure. A summary of the effects of blood glucose-lowering drugs other than glitazones on the risk of heart failure in routine clinical practice is lacking. The objective of this study was to conduct a systematic review and meta-analysis of observational studies on the risk of heart failure when using blood glucose-lowering drugs.

Methods

We systematically identified and reviewed cohort and case–control studies in which the main exposure of interest was noninsulin blood glucose-lowering medications in patients with T2DM. We searched Medline, Embase, and the Cochrane Library to identify publications meeting prespecified eligibility criteria. The quality of included studies was assessed with the Newcastle-Ottawa Scale and the RTI item bank. Results were combined using fixed and random-effects models when at least 3 independent data points were available for a drug-drug comparison.

Results

The summary relative risk of heart failure in rosiglitazone users versus pioglitazone users (95% CI) was 1.16 (1.05-1.28) (5 cohort studies). Heterogeneity was present (I² = 66%). For new users (n = 4) the summary relative risk was 1.21 (1.14-1.30) and the heterogeneity was reduced (I² = 31%);. The summary relative risk for rosiglitazone versus metformin was 1.36 (95% CI, 1.17-1.59) (n = 3). The summary relative risk (95% CI) of heart failure in sulfonylureas users versus metformin users was 1.17 (95% CI, 1.06-1.29) (5 cohort studies; I² = 24%) and 1.22 (1.02-1.46) when restricted to new users (2 studies).

Information on other comparisons was very scarce. Information on dose and duration of treatment effects was lacking for most comparisons. Few studies accounted for disease severity; therefore, confounding by indication might be present in the majority of the within-study comparisons of this meta-analysis.

Conclusions

Use of glitazones and sulfonylureas was associated with an increased risk of heart failure compared with metformin use. However, indication bias cannot be ruled out. Ongoing large multidatabase studies will help to evaluate the risk of heart failure in treated patients with diabetes, including those using newer blood glucose-lowering therapies.

【 授权许可】

   
2014 Varas-Lorenzo et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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