Can dapagliflozin be added for heart failure in a patient receiving glimepiride and insulin glargine (Lantus)?

From the Guidelines

Adding dapagliflozin to a patient's regimen of glimepiride and glargine insulin is recommended for heart failure management, as it has been shown to reduce the risk of worsening heart failure and cardiovascular death, regardless of diabetes status 1. When considering the addition of dapagliflozin, it is crucial to be aware of the potential increased risk of hypoglycemia when combined with sulfonylureas like glimepiride and insulin.

• Key considerations include:
  • Reducing the glimepiride dose by 25-50% when initiating dapagliflozin to minimize hypoglycemic risk
  • Monitoring blood glucose levels more frequently during the initial weeks of therapy
  • Educating patients on hypoglycemia symptoms and management
  • Watching for volume depletion, particularly in elderly patients or those on diuretics
  • Monitoring renal function, as dapagliflozin's effectiveness decreases with declining kidney function (it is not recommended if eGFR is below 30 ml/min/1.73m²) 1. The mechanism of dapagliflozin, which involves increasing glucose excretion through the kidneys, also has beneficial effects on cardiac preload and afterload, making it a valuable addition for heart failure patients, despite the need for careful management with existing glucose-lowering medications 1.
• The benefits of dapagliflozin in heart failure management have been consistently demonstrated across several studies, including the DAPA-HF and DELIVER trials, which showed significant reductions in worsening heart failure and cardiovascular death 1. Given the strong evidence supporting the use of dapagliflozin in heart failure, initiating dapagliflozin at a typical dose of 10 mg once daily, with careful monitoring and adjustment of the patient's glimepiride and insulin regimen as needed, is a reasonable approach to managing heart failure in patients with type 2 diabetes 1.

From the FDA Drug Label

The DAPA-HF trial was an international, multicenter, randomized, double-blind, placebo-controlled trial in patients with heart failure [New York Heart Association (NYHA) functional class II-IV] with reduced ejection fraction [left ventricular ejection fraction (LVEF) 40% or less] to determine whether dapagliflozin reduces the risk of cardiovascular death and hospitalization for heart failure.

In both trials, all three components of the primary composite endpoint individually contributed to the treatment effect. In both trials, the dapagliflozin and placebo event curves separated early and continued to diverge over the trial period

The patient can be given dapagliflozin for heart failure while receiving glimepiride and glargine insulin, as there is no direct contraindication in the provided drug labels.

• Key points:
  • Dapagliflozin has been shown to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with heart failure.
  • The treatment effect of dapagliflozin was consistent across various subgroups, including patients with type 2 diabetes mellitus.
  • However, it is essential to monitor the patient's condition and adjust the treatment plan as needed, considering the potential interactions between dapagliflozin and other medications, such as glimepiride and glargine insulin 2 2.

From the Research

Dapagliflozin for Heart Failure

• Dapagliflozin has been shown to be effective in reducing hospitalizations for heart failure in patients with type 2 diabetes mellitus treated with SGLT2 inhibitors 3.
• The DAPA-HF trial demonstrated that dapagliflozin was superior to placebo at preventing CV deaths and HF events, with consistent results across subgroups including patients with and without diabetes 3.
• The benefit of dapagliflozin on morbidity and mortality in heart failure with reduced ejection fraction (HFrEF) was not modified by baseline kidney function, and dapagliflozin slowed the rate of decline in eGFR 4.

Combination with Glimepiride and Glargine Insulin

• There is no direct evidence in the provided studies on the specific combination of dapagliflozin with glimepiride and glargine insulin.
• However, glimepiride is a second-generation sulfonylurea that stimulates pancreatic β cells to release insulin, and it can be combined with other antihyperglycemic agents, including insulin, in patients who are not adequately controlled by sulfonylureas alone 5.
• Dapagliflozin has been shown to be effective in patients with HFrEF, regardless of their diabetes status, and its use may be beneficial in patients with heart failure who are also receiving other antihyperglycemic agents 3, 4.

Safety and Efficacy

• The safety and efficacy of dapagliflozin in patients with heart failure and deterioration in renal function have been evaluated, and the results suggest that the benefit-to-risk ratio may favor continuation of dapagliflozin treatment in these patients 6.
• Comparative effectiveness studies have shown that individual SGLT2 inhibitors, including dapagliflozin, demonstrate comparable cardiovascular effectiveness at clinically effective doses 7.