What is the best antidiabetic medication to initiate in a patient with heart failure and elevated hemoglobin A1c (HbA1c) of 8% despite being on metformin (Metformin)?

From the Guidelines

For a patient with heart failure and an HbA1c of 8% despite metformin therapy, an SGLT2 inhibitor such as empagliflozin (Jardiance) 10 mg daily or dapagliflozin (Farxiga) 10 mg daily would be the best next antidiabetic medication to add. These medications have demonstrated significant cardiovascular benefits specifically in heart failure patients, reducing hospitalizations and cardiovascular mortality regardless of diabetes status, as shown in the EMPA-REG OUTCOME study 1. SGLT2 inhibitors work by preventing glucose reabsorption in the kidneys, promoting glucose excretion in urine, which helps lower blood glucose levels. They also provide additional benefits for heart failure patients by reducing cardiac preload and afterload, decreasing cardiac workload, and promoting beneficial cardiac remodeling. These medications typically lower HbA1c by 0.5-0.8%, have a low risk of hypoglycemia, promote modest weight loss, and can provide renal protection. Common side effects include genital mycotic infections and volume depletion, so patients should be counseled on proper genital hygiene and monitored for signs of dehydration, especially if they're on diuretics for heart failure. The 2023 standards of care in diabetes also support the use of SGLT2 inhibitors in patients with heart failure, highlighting their benefits in reducing the risk of heart failure hospitalization and cardiovascular mortality 1. In contrast, other antidiabetic medications such as thiazolidinediones are associated with an increased risk of heart failure and should be avoided in patients with heart failure, as recommended by the 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases 1. Similarly, the use of DPP-4 inhibitors such as saxagliptin is not recommended due to their potential to increase the risk of heart failure hospitalization, as shown in the SAVOR-TIMI 53 study 1. Therefore, based on the most recent and highest quality evidence, SGLT2 inhibitors are the preferred choice for patients with heart failure and diabetes.

Some key points to consider when prescribing SGLT2 inhibitors include:

• Monitoring for signs of dehydration, especially in patients on diuretics
• Counseling on proper genital hygiene to prevent mycotic infections
• Regular monitoring of renal function and adjusting the dose as needed
• Considering the potential benefits of SGLT2 inhibitors in reducing cardiovascular mortality and heart failure hospitalization
• Avoiding the use of thiazolidinediones and saxagliptin in patients with heart failure due to their potential to increase the risk of heart failure hospitalization.

Overall, the use of SGLT2 inhibitors in patients with heart failure and diabetes is supported by strong evidence and should be considered as a first-line treatment option to improve outcomes and reduce the risk of cardiovascular mortality and heart failure hospitalization.

From the FDA Drug Label

At the end of treatment, INVOKANA 300 mg provided greater HbA1c reduction compared to sitagliptin 100 mg when added to metformin HCl and sulfonylurea (p<0.05). INVOKANA 300 mg resulted in a mean percent change in body weight from baseline of -2.5% compared to +0.3% with sitagliptin 100 mg. A mean change in systolic blood pressure from baseline of -5.06 mmHg was observed with INVOKANA 300 mg compared to +0.85 mmHg with sitagliptin 100 mg

The best antidiabetic to start on someone with heart failure and HbA1c of 8% despite being on metformin is canagliflozin (INVOKANA), as it has been shown to provide greater HbA1c reduction and improvements in body weight and systolic blood pressure compared to other antidiabetic agents when added to metformin.

• Key benefits of canagliflozin include:
  • Greater HbA1c reduction
  • Weight loss
  • Reduction in systolic blood pressure 2

From the Research

Antidiabetic Treatment for Heart Failure and HbA1c of 8%

• The patient is already on metformin, but HbA1c levels remain at 8% despite treatment 3.
• Considering the addition of another antidiabetic medication, SGLT2 inhibitors have shown promise in reducing cardiovascular risk and improving outcomes in patients with heart failure 4, 5, 6.
• Empagliflozin, a SGLT2 inhibitor, has been shown to reduce the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure 4, 5, 6.
• The combination of a SGLT2 inhibitor and a GLP-1 receptor agonist may have additive effects on lowering HbA1c levels, systolic blood pressure, and body weight, as well as reducing cardiac risk and renal decompensation 7.

Potential Treatment Options

• Empagliflozin, as it has been shown to be effective in reducing cardiovascular risk and improving outcomes in patients with heart failure 4, 5, 6.
• Combination therapy with a GLP-1 receptor agonist and a SGLT2 inhibitor, such as empagliflozin, may be considered to achieve better glycemic control and reduce cardiovascular risk 7.
• Other SGLT2 inhibitors, such as dapagliflozin, may also be considered as alternative options 4.

Considerations

• The patient's current HbA1c level of 8% may not necessitate the use of insulin as the first-line treatment, as other antidiabetic medications may be effective in achieving glycemic control 3.
• The choice of antidiabetic medication should be individualized based on the patient's specific needs and medical history.