Author + information
- Walter J. Paulus, MD, PhD∗ ( and )
- Elisa Dal Canto, MD
- ↵∗Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, O|2 Building 10W13, De Boelelaan 1118, 1081 HV Amsterdam, the Netherlands
Dr. Jonnalagadda and colleagues express concern about the absence of a beneficial effect of tight glycemic control on diastolic left ventricular function, the use of metformin in patients with both diabetes mellitus (DM) and heart failure (HF), and the unique mode of action of sodium glucose cotransporter-2 inhibitors (1). These concerns are valid.
There is indeed uncertainty about glycemic control in patients with both DM and HF. This finding was again evident in a recent case-control study, in which glycemic control, measured by glycosylated hemoglobin levels, showed a U-shaped relationship with risk of HF hospitalization and HF mortality (2).
As regards metformin, it is currently recommended as first-line therapy for the management of DM in patients with HF by the European Society of Cardiology HF Guidelines with a Class IIa, Level of Evidence: C recommendation. Metformin activates adenosine monophosphate–activated protein kinase, thereby inhibiting hepatic gluconeogenesis and stimulating endothelial nitric oxide synthase. In a comprehensive review of observational studies, it was associated with improved clinical outcomes when compared with other agents in the setting of DM and HF (3).
With respect to the sodium glucose cotransporter-2 inhibitors, they indeed have a distinct mode of action that differs from other classes of antidiabetic agents. The recently observed left ventricular dilatation with vildagliptin in HF with reduced ejection fraction is reason for concern and suggests vildagliptin to accentuate the DM-induced eccentric left ventricular remodeling observed in HF with reduced ejection fraction (4).
Taken together, DM therapy in HF remains challenging and should take into account HF phenotypes.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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