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Glucose-lowering therapies, strategies may increase heart failure
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The use of medications or other strategies to lower glucose could put patients at an increased risk for heart failure compared with usual care, according to research published in The Lancet Diabetes & Endocrinology.
“Patients randomized to new or more intensive blood sugar-lowering drugs or strategies to manage diabetes showed an overall 14% increased risk for heart failure,” Jacob A. Udell, MD, of the University Health Network and Women’s College Hospital, Toronto, said in a news release.
The magnitude of risk appears to be dependent on glucose-lowering method, with weight gain potentially playing a role, according to researchers.
“This increased risk was directly associated with the type of diabetes therapy that was chosen, with some drugs more likely to cause heart failure than others, compared with placebo or standard care,” Udell said.
Udell and colleagues conducted a comprehensive meta-analysis of 14 large randomized controlled trials (mean duration, 4.3 ± 2.3 years) of glucose-lowering drugs or strategies that evaluated cardiovascular outcomes, identified through a search of Ovid Medline, the Cochrane Library and meeting abstracts up to Feb. 20.
The review involved 95,502 patients, of whom 4% developed a heart failure event and 9.8% endured a major adverse CV event. The investigators used random-effects models to derive pooled RRs.
Glucose-lowering drugs or strategies were associated with a 0.5% (standard deviation [SD] = 0.33) HbA1c decrease and a 1.7-kg (SD = 2.8) weight increase; both increased the risk for heart failure compared with standard care (RR = 1.14; 95% CI, 1.01-1.3).
Effect strength varied based on glucose-lowering method (P for interaction = .00021). The risk was high with peroxisome proliferator-activated receptor agonists (six trials; RR = 1.42; 95% CI, 1.15-1.76), intermediate with DPP-IV inhibitors (two trials; RR = 1.25; 95% CI, 1.08-1.45) and neutral with insulin glargine (one trial; RR = 0.9; 95% CI, 0.77-1.05).
The development of heart failure was not associated with target-based intensive glycemic control strategies (four trials; RR = 1; 95% CI, 0.88-1.13) or intensive weight loss (one trial; RR = 0.8; 95% CI, 0.62-1.04).
“While some drugs showed an increased risk, other strategies tested, such as intensive weight loss to control blood sugar, showed a trend toward a lower risk for heart failure,” Michael Farkouh, MD, chair of the Peter Munk Centre of Excellence in Multinational Clinical Trials, where the study was conducted, said in the release.
Based on meta-regression analysis, for every 1 kg of weight gain linked to glucose-lowering drugs or strategies, the risk for heart failure increased 7.1% (95% CI, 1-13.6) compared with standard care (P = .022).
The relative increase in the risk for heart failure outweighed the 5% reduction in myocardial infarction, according to the release. Further, at a mean follow-up of 4 years, one additional hospital admission for heart failure was seen per approximately 200 patients treated.
In an accompanying commentary, Iwan C. C. van der Horst, MD, and Frederik Keus, MD, both of the department of critical care, University Medical Center Groningen, Netherlands, noted it may not be appropriate to draw conclusions with specific interventions due to the variation between the trials analyzed.
“These risks of errors, and the substantial heterogeneity among included trials, suggest caution is needed before concluding that all glucose-lowering drugs and strategies in general are associated with an increased risk of heart failure,” they wrote. – by Allegra Tiver
Disclosure: Udell reports training with a group that received grant support from
AstraZeneca and Bristol-Myers Squibb prior to the current study, grants from the American College of Cardiology Foundation, and fees for consultancy from Cisbio Bioassays and Novartis outside this work.
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