What alternative agent can be added to Jardiance (Empagliflozin) 25mg, Diamicron (Gliclazide) 120mg, and metformin 2000mg to help control a patient's elevated Hemoglobin A1C (HbA1c) level, considering intolerance to Ozempic (Semaglutide) and a history of cardiac disease?

From the Guidelines

For a patient with an HbA1c of 11.2% who is already on Jardiance 25mg, Diamicron 120mg, and metformin 2000mg, and cannot tolerate Ozempic, I would recommend adding a GLP-1 receptor agonist such as liraglutide or semaglutide, as they have demonstrated cardiovascular benefits in patients with type 2 diabetes and cardiovascular disease 1. Given the patient's cardiac history, it is crucial to prioritize medications that have shown cardiovascular benefits. The 2020 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases recommend the use of GLP-1 receptor agonists such as liraglutide, semaglutide, or dulaglutide in patients with type 2 diabetes and cardiovascular disease to reduce cardiovascular events 1. Some key points to consider when adding a new medication to this patient's regimen include:

• The patient's high HbA1c of 11.2% indicates poor glycemic control that requires prompt intervention
• The need to balance the benefits of glycemic control with the potential risks of hypoglycemia and other adverse effects
• The importance of regular monitoring of blood glucose levels and kidney function after initiating the new medication
• The potential for GLP-1 receptor agonists to provide cardiovascular benefits beyond their glucose-lowering effects, as discussed in the 2024 standards of care in diabetes 1 Alternatively, if a GLP-1 receptor agonist is not suitable, an SGLT2 inhibitor such as empagliflozin or canagliflozin could be considered, as they have also demonstrated cardiovascular benefits in patients with type 2 diabetes and cardiovascular disease 1. However, given the patient is already on Jardiance (empagliflozin), this option may not be feasible. It is essential to weigh the potential benefits and risks of each medication option and to consider the patient's individual characteristics, such as their cardiac history and current medication regimen, when making a treatment decision.

From the FDA Drug Label

SITAGLIPTIN/METFORMIN 50/850MG

The FDA drug label does not answer the question.

From the Research

Treatment Options for Type 2 Diabetes

Given the patient's current medication regimen and intolerance to Ozempic, alternative agents can be considered to help control her HbA1C level of 11.2, taking into account her cardiac history.

• DPP-4 Inhibitors: These are a class of oral antihyperglycemic agents that enhance the body's ability to regulate blood glucose by increasing the active levels of incretins, such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) 2. They have been shown to be effective in reducing HbA1c levels, with an average reduction ranging between -0.5 to -1.0% with monotherapy 3. Examples include sitagliptin, vildagliptin, saxagliptin, and alogliptin.
• SGLT2 Inhibitors: Sodium-glucose cotransporter 2 inhibitors have been associated with cardiovascular benefits and may offer an alternative for patients with type 2 diabetes, especially considering the patient's cardiac history 4. They have been shown to reduce the risk of modified major adverse cardiovascular events (MACE) and hospitalization for heart failure (HHF) compared to DPP-4 inhibitors, regardless of baseline HbA1c levels 4. An example is dapagliflozin, which has been compared to DPP-4 inhibitors in terms of effectiveness on a composite endpoint of glycaemic and extraglycaemic effectiveness 5.

Considerations for Cardiac History

When selecting an additional agent for a patient with a cardiac history, it's crucial to consider the cardiovascular safety profile of the medication.

• DPP-4 inhibitors have undergone rigorous cardiovascular outcome trials (CVOTs), and while they are generally considered safe, there is a noted higher risk of hospitalization from heart failure with saxagliptin 3.
• SGLT2 inhibitors have demonstrated cardiovascular benefits, including a reduced risk of MACE and HHF, making them a potentially favorable option for patients with cardiac history 4.

Decision Making

The choice between adding a DPP-4 inhibitor or an SGLT2 inhibitor should be based on the patient's specific clinical profile, including her cardiac history and current medication regimen. Given the patient's intolerance to Ozempic, a DPP-4 inhibitor like sitagliptin or alogliptin, or an SGLT2 inhibitor such as dapagliflozin, could be considered as an add-on therapy to help achieve better glycemic control, with careful monitoring of her cardiac status and potential side effects 6, 5, 2, 3, 4.