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Sulfonylureas and the Risks of Cardiovascular Events and Death: A Methodological Meta-Regression Analysis of the Observational Studies

Diabetes care, 2017-05, Vol.40 (5), p.706-714 [Peer Reviewed Journal]

2017 by the American Diabetes Association. ;Copyright American Diabetes Association May 2017 ;ISSN: 0149-5992 ;EISSN: 1935-5548 ;DOI: 10.2337/dc16-1943 ;PMID: 28428321

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Title:
Sulfonylureas and the Risks of Cardiovascular Events and Death: A Methodological Meta-Regression Analysis of the Observational Studies
Author: Azoulay, Laurent ; Suissa, Samy
Subjects: Bias ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - etiology ; Cardiovascular Diseases - mortality ; Comparators ; Death ; Design ; Diabetes mellitus ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - drug therapy ; Drug development ; Drugs ; Heterogeneity ; Humans ; Hypoglycemic Agents - adverse effects ; Hypoglycemic Agents - therapeutic use ; Medical treatment ; Metformin ; Metformin - adverse effects ; Metformin - therapeutic use ; Mortality ; Observational studies ; Regression Analysis ; Reviews ; Risk assessment ; Risk Factors ; Sulfonylurea Compounds - adverse effects ; Sulfonylurea Compounds - therapeutic use ; Treatment Outcome
Is Part Of: Diabetes care, 2017-05, Vol.40 (5), p.706-714
Description: Recent randomized trials have compared the newer antidiabetic agents to treatments involving sulfonylureas, drugs associated with increased cardiovascular risks and mortality in some observational studies with conflicting results. We reviewed the methodology of these observational studies by searching MEDLINE from inception to December 2015 for all studies of the association between sulfonylureas and cardiovascular events or mortality. Each study was appraised with respect to the comparator, the outcome, and study design-related sources of bias. A meta-regression analysis was used to evaluate heterogeneity. A total of 19 studies were identified, of which six had no major design-related biases. Sulfonylureas were associated with an increased risk of cardiovascular events and mortality in five of these studies (relative risks 1.16-1.55). Overall, the 19 studies resulted in 36 relative risks as some studies assessed multiple outcomes or comparators. Of the 36 analyses, metformin was the comparator in 27 (75%) and death was the outcome in 24 (67%). The relative risk was higher by 13% when the comparator was metformin, by 20% when death was the outcome, and by 7% when the studies had design-related biases. The lowest predicted relative risk was for studies with no major bias, comparator other than metformin, and cardiovascular outcome (1.06 [95% CI 0.92-1.23]), whereas the highest was for studies with bias, metformin comparator, and mortality outcome (1.53 [95% CI 1.43-1.65]). In summary, sulfonylureas were associated with an increased risk of cardiovascular events and mortality in the majority of studies with no major design-related biases. Among studies with important biases, the association varied significantly with respect to the comparator, the outcome, and the type of bias. With the introduction of new antidiabetic drugs, the use of appropriate design and analytical tools will provide their more accurate cardiovascular safety assessment in the real-world setting.
Publisher: United States: American Diabetes Association
Language: English
Identifier: ISSN: 0149-5992
EISSN: 1935-5548
DOI: 10.2337/dc16-1943
PMID: 28428321
Source: Geneva Foundation Free Medical Journals at publisher websites
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Sulfonylureas and the Risks of Cardiovascular Events and Death: A Methodological Meta-Regression Analysis of the Observational Studies

2017 by the American Diabetes Association. ;Copyright American Diabetes Association May 2017 ;ISSN: 0149-5992 ;EISSN: 1935-5548 ;DOI: 10.2337/dc16-1943 ;PMID: 28428321

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