Do heart failure medications increase blood glucose levels?

From the Guidelines

Heart failure medications can have varying effects on blood glucose levels, with some increasing glucose levels, while others have neutral or beneficial effects, and SGLT2 inhibitors actually improving glucose control, as demonstrated in the most recent study from 2023 1.

Effects of Heart Failure Medications on Blood Glucose

Some heart failure medications, such as thiazolidinediones, have a strong and consistent relationship with increased risk of heart failure and should be avoided in patients with symptomatic heart failure 1.

• Beta-blockers like carvedilol, metoprolol, and bisoprolol may worsen glucose control by decreasing insulin sensitivity and masking hypoglycemia symptoms.
• Thiazide diuretics such as hydrochlorothiazide can raise blood glucose, especially at higher doses (>25mg daily).
• Loop diuretics like furosemide may also negatively impact glucose metabolism. In contrast, ACE inhibitors (like lisinopril, enalapril) and ARBs (such as losartan, valsartan) generally have neutral or slightly beneficial effects on glucose control 1.

Beneficial Effects of SGLT2 Inhibitors

SGLT2 inhibitors, such as empagliflozin, have been shown to improve glucose levels and reduce the risk of heart failure hospitalization, with a significant 35% reduction in hospitalization for heart failure compared with placebo, as demonstrated in the EMPA-REG OUTCOME study 1.

• The EMPEROR-Preserved trial also showed a 21% reduction in the composite cardiovascular death or hospitalization for heart failure with empagliflozin 10 mg daily versus placebo 1.
• A large recent meta-analysis including data from EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, DELIVER, and Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes assessed the effects of empagliflozin 10 mg once daily versus placebo, further supporting the beneficial effects of SGLT2 inhibitors on glucose control and heart failure outcomes 1. Patients with diabetes or prediabetes who take heart failure medications should monitor their blood glucose regularly, especially when starting new medications or adjusting doses, and healthcare providers may need to adjust diabetes medications accordingly to maintain optimal glucose control.

From the FDA Drug Label

5.6 Glycemic Control in Type 2 Diabetes In general, β-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia. Nonselective β-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels Patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be cautioned about these possibilities. Studies designed to examine the effects of Carvedilol Tablet on glycemic control in patients with diabetes and heart failure have not been conducted In a study designed to examine the effects of Carvedilol Tablet on glycemic control in a population with mild-to-moderate hypertension and well-controlled type 2 diabetes mellitus, Carvedilol Tablet had no adverse effect on glycemic control, based on HbA1c measurements No clinically relevant changes were noted in fasting serum glucose in hypertensive patients.

The FDA drug label does not provide direct evidence that heart failure medications, specifically carvedilol, increase blood glucose levels. In fact, the label states that carvedilol had no adverse effect on glycemic control in a study of patients with mild-to-moderate hypertension and well-controlled type 2 diabetes mellitus. Additionally, no clinically relevant changes were noted in fasting serum glucose in hypertensive patients 2.

From the Research

Heart Failure Medications and Blood Glucose Levels

• The relationship between heart failure medications and blood glucose levels is complex and depends on the specific medication and patient population.
• Some studies suggest that certain heart failure medications, such as beta-blockers, may have a neutral or even beneficial effect on blood glucose levels 3, 4.
• Sodium-glucose co-transporter 2 (SGLT2) inhibitors, which are used to treat type 2 diabetes, have been shown to have cardiorenal benefits and reduce the risk of hospitalization for heart failure, and may even reduce the risk of incident type 2 diabetes in people with heart failure without diabetes 5, 6, 7.
• However, the effect of SGLT2 inhibitors on blood glucose levels in patients with heart failure without diabetes is still being studied, and more research is needed to fully understand their impact 7.
• The use of beta-blockers in patients with heart failure is still controversial, and their effect on blood glucose levels is not fully understood, with some studies suggesting a potential benefit and others suggesting no effect 3, 4.

Specific Medications and Their Effects on Blood Glucose Levels

• Beta-blockers: may have a neutral or beneficial effect on blood glucose levels, but their mechanism of action is not fully understood 3, 4.
• SGLT2 inhibitors: may reduce the risk of incident type 2 diabetes in people with heart failure without diabetes, and have cardiorenal benefits 5, 6, 7.
• Renin-angiotensin-aldosterone system inhibitors: may have a beneficial effect on blood glucose levels, but their impact is not fully understood 3.

Patient Populations and Their Response to Heart Failure Medications

• Patients with heart failure and diabetes: may benefit from SGLT2 inhibitors, which have been shown to reduce the risk of hospitalization for heart failure and cardiovascular mortality 5, 6.
• Patients with heart failure without diabetes: may benefit from SGLT2 inhibitors, which may reduce the risk of incident type 2 diabetes 7.
• Patients with prediabetes: may benefit from SGLT2 inhibitors, which may reduce the risk of incident type 2 diabetes 7.