What are the recommended oral medications for type 2 diabetes (T2D) in addition to insulin for a patient with severely elevated hemoglobin A1c (HbA1c) levels?

From the Guidelines

For a patient with type 2 diabetes and HbA1c >14% who is already on insulin, I recommend adding metformin as the first-line oral medication, typically starting at 500mg once or twice daily and titrating up to 1000mg twice daily as tolerated. This recommendation is based on the most recent and highest quality study available, which emphasizes the importance of individualized treatment approaches and the role of metformin as the preferred initial pharmacological agent for type 2 diabetes 1. The study also highlights the benefits of SGLT2 inhibitors and GLP1 agonists in reducing all-cause mortality and major adverse cardiovascular events (MACE) compared to usual care, making them suitable alternatives or additions to metformin if necessary 1. Key considerations in the management of type 2 diabetes include:

• Starting with metformin due to its efficacy, safety, and potential to reduce cardiovascular events
• Considering SGLT2 inhibitors (like empagliflozin or dapagliflozin) or GLP1 agonists (like semaglutide) for their benefits in reducing cardiovascular risk and improving glycemic control
• Potential addition of other agents such as DPP4 inhibitors or pioglitazone for patients with very poor glycemic control
• Monitoring for hypoglycemia, especially in patients on insulin, and adjusting insulin doses as needed
• Ensuring patient education on lifestyle modifications, regular blood glucose monitoring, and recognizing signs of hypoglycemia as foundational components of diabetes management. It's crucial to tailor the treatment approach to the individual patient's needs, preferences, and clinical characteristics, as emphasized in recent guidelines and studies 1.

From the FDA Drug Label

JARDIANCE used in combination with insulin (with or without metformin and/or sulfonylurea) provided statistically significant reductions in HbA1c and FPG compared to placebo after both 18 and 78 weeks of treatment A total of 563 patients with type 2 diabetes inadequately controlled on multiple daily injections (MDI) of insulin (total daily dose >60 IU), alone or in combination with metformin, participated in a double-blind, placebo-controlled study to evaluate the efficacy of JARDIANCE as add-on therapy to MDI insulin over 18 weeks JARDIANCE 10 mg or 25 mg daily used in combination with MDI insulin (with or without metformin) provided statistically significant reductions in HbA1c compared to placebo after 18 weeks of treatment

The recommended oral medications for type 2 diabetes (T2D) in addition to insulin for a patient with severely elevated hemoglobin A1c (HbA1c) levels are:

• Empagliflozin (JARDIANCE): 10 mg or 25 mg daily, in combination with insulin, with or without metformin and/or sulfonylurea.
• Metformin: can be used in combination with JARDIANCE and insulin.
• Sulfonylurea: can be used in combination with JARDIANCE and insulin. 2

From the Research

Recommended Oral Medications for Type 2 Diabetes

In addition to insulin, several oral medications can be used to manage type 2 diabetes (T2D) in patients with severely elevated hemoglobin A1c (HbA1c) levels. The following are some of the recommended options:

• Metformin: As the first-line oral medication for glycemic control in patients with T2D, metformin has been shown to lower HbA1c levels by 1.12% compared to placebo 3.
• Empagliflozin: A sodium glucose cotransporter 2 inhibitor, empagliflozin has been found to be non-inferior to glimepiride in reducing HbA1c levels, with a mean difference of -0.11% at week 104 4.
• Glimepiride: A sulfonylurea, glimepiride can be used as an add-on to metformin in patients with T2D who have not achieved good glycemic control on metformin alone 4.
• Dapagliflozin: Another sodium glucose cotransporter 2 inhibitor, dapagliflozin has been shown to reduce HbA1c levels by 2% from baseline levels of 9.1% 5.
• Canagliflozin: A sodium glucose cotransporter 2 inhibitor, canagliflozin has been found to reduce HbA1c levels by 1.8% from baseline levels of 9.6% 5.

Considerations for Treatment

When selecting an oral medication for T2D, several factors should be considered, including:

• HbA1c level: Patients with higher HbA1c levels may require more aggressive treatment, such as the addition of insulin or a glucagon-like peptide-1 receptor agonist 6, 5.
• Comorbidities: Patients with certain comorbidities, such as hypertension, hyperlipidemia, or renal disease, may require more careful consideration of treatment options 7.
• Age: Older patients may be less likely to receive add-on therapy, despite having suboptimal glycemic control 7.
• Symptomatic hyperglycemia: Patients with symptomatic hyperglycemia may require more urgent treatment, such as the initiation of insulin therapy 6.