Current treatment of Diabetes in Heart Failure
The number of acute and chronic HF patients with diabetes (DM) increased tremendously over the last decade. The prevalence of DM in these patients now ranges between 13 and 47% and is even higher in HF patients with preserved ejection fraction (25-33%). Both diseases are deleterious, and prognosis is even worse when the two co-exist. ‘Diabetes and heart failure are fatal twins’, states professor Voors.
Medication that reduces glucose and haemoglobulin A1c (HbA1c) levels may have devastating effects on heart function. Both too loose and too strict control of HbA1c may be harmful, as a U-shaped relation has been reported between death and Hb1Ac level upon antidiabetic treatment1. It is therefore crucial to define and select the most optimal drug and dose. Prof. Voors provided an overview of currently available antidiabetic drugs, their effect on HF and current guideline recommendations on treatment.
‘Diabetes and heart failure are fatal twins’
First, clinical data were presented that demonstrated the inferior prognosis for DM patients with advanced HF and who were treated with insulin compared to those that did not get insulin2. However, Voors noted that these data may be biased, as insulin-treated patients generally have more severe DM. Nevertheless, the CHARM trial3 supports the potential harmful effects of insulin, since insulin-treated DM was the third strongest predictive factor of all-cause mortality in a wide variety of HF patients.
Second, the relation of antidiabetic sulfonylureas to HF was discussed. A direct interaction has not been studied, however it has been shown that sulfonylurea-treated patients experienced HF more frequently compared to patients treated with the antidiabetic metformin4.
Metformin has been investigated in quite a number of studies, including two meta-analyses of several antidiabetic drugs. These data demonstrated that metformin was actually the only drug that did not show any harm and was even suggested to be beneficial for HF patients5, 6.
In contrast, a meta-analysis with various antidiabetic thiazolidinediones (TZDs) in prediabetic and diabetic patients showed an increased risk of congestive HF and cardiovascular (CV) death in almost all studies7. Therefore, the FDA officially warns for treatment with TZDs in DM patients with increased risk of HF: it is discouraged and should be handled with care.
At last, the effect of GLP-1 receptor antagonists and DPP-4 inhibitors on HF were discussed, but strong evidence is currently lacking. GLP-1 analogues may increase the risk of CV events and worsening HF8, but the 2016 ESC HF guidelines state that no safety data in HF is available. Saxagliptin showed a significant increase in HF hospitalisation in the SAVOR-TIMI 53 trial, but this was not confirmed for other DPP-4 inhibitors9.
Voors concluded that metformin is the antidiabetic treatment of choice in patients with HF, although it cannot be used in all DM patients. All other drugs either worsen HF, should be
used with caution or are even discouraged, or lack data that ensure its safety.