Heart Failure Risk with Diabetes Mellitus Treatment in Patients

Diabetes is a risk factor of both hypertension and coronary artery disease due to increased systemic pressures and increased atherosclerosis, increasing the risk of cardiomyopathy and congestive heart failure. There is a high prevalence of diabetes mellitus among heart failure patients with one study showing a 40% of hospitalized heart failure patients having comorbid diabetes mellitus. The association of heart failure in diabetes mellitus patients increases mortality rates by 10 times compared to those patients without heart failure. Glycemic control in diabetes mellitus patients may lower the risk of heart failure, however close monitoring is necessary as treatment of diabetes mellitus may also increase the risk of heart failure or worsen co-existing heart failure in these patients.

Some evidence suggests strict blood glucose control in heart failure patients may increase the risk of cardiovascular events secondary to hypoglycemia. The UK Prospective Diabetes Study (UKPDS) contradicted this by showing a decreased risk of heart failure by 16% in diabetic patients with lowering of A1C by 1%. Another study showed improvement in A1C levels resulted in improved left ventricular systolic function. Yet various other studies have shown no significant improvement in heart failure outcomes with strict blood glucose control.

Insulin treatment is associated with the highest incidence of heart failure among diabetes mellitus patients. This may be secondary to comorbid conditions in patients requiring insulin therapy such as coronary artery disease, hypertension, or chronic kidney disease however the physiologic effects of insulin therapy also contribute to sodium retention and thus can contribute to fluid retention.

Metformin is considered cardio-protective with improved cardiovascular outcomes when used in type 2 diabetes mellitus patients. There is also added benefit of weight loss with metformin use. Although some studies have shown a decreased morbidity and mortality rates among heart failure patients treated with metformin, this is more difficult to ascertain as these patients may have less severe diabetes mellitus. Caution should be used with metformin use among decompensated heart failure patients especially with fluctuating renal function due to risk of lactic acidosis.

Sulphonylureas can cause weight gain but do not contribute to fluid retention. The impact of sulphonylureas on morbidity and mortality rates in heart failure patients has not been well studied. Some studies show there is no increased incidence of heart failure among sulphonylurea treated patients. Other studies show an increased risk of heart failure and hospitalization compared with metformin therapy. More studies are needed to determine the risk of sulphonylurea treatment in heart failure patients.

Thiazolidinediones (TZDs) can cause peripheral vasodilation and increased sodium reabsorption resulting in weight gain and edema. There is an increased incidence of heart failure among therapy with TZDs. Treatment with TZDs is associated with heart failure exacerbation and hospitalization. American Heart Association recommends against the use of TZDs in patients with NYHA class III and IV and used with caution in class I and II patients. The FDA has also released a black box warning against the use of TZDs in heart failure.

The use of sodium-glucose co-transporter 2 inhibitors has been shown to be beneficial to heart failure patients by lowering blood pressure, diuresis, and weight loss. Studies have shown a decreased risk of cardiovascular events and mortality rates with treatment of empagliflozin. Similar trials with canagliflozin have shown decreased hospitalization rates in heart failure patients. Currently trials are being done to study the use of these medications in patients with known heart failure.

Patients with diabetes mellitus are at risk for cardiac events including the risk of congestive heart failure. Treatment of diabetes mellitus is important to decrease risk of long-term microvascular and macrovascular complications. Clinicians should be aware of the increased risk of heart failure with treatment of diabetes mellitus, especially with the use of TZDs, and importance of monitoring and assessing for heart failure. Future studies are needed to determine the benefit of sodium-glucose co-transporter 2 inhibitors.

References

Heart failure outcomes in clinical trials of glucose-lowering agents in patients with diabetes by Fitchett, D. H., Udell, J. A., & Inzucchi, S. E.

Heart failure epidemiology, pathophysiology, and management of heart failure in diabetes mellitus by Jorsal, A., Wiggers, H., & McMurray, J. J. V.