What is a good starting point for medication for a patient with a Hemoglobin A1c (HbA1c) level of severely elevated blood glucose?

From the Guidelines

For an A1c of 14.9, initiating pharmacologic therapy with metformin and basal insulin is recommended, as this combination approach can help quickly achieve glycemic control and reduce the risk of complications. According to the most recent guidelines 1, metformin is the initial pharmacologic treatment of choice if renal function is normal, and basal insulin should be considered for patients with marked hyperglycemia.

Key Considerations

• Metformin should be started at a dose of 500 mg twice daily and increased to 1000 mg twice daily over 2-4 weeks as tolerated 1.
• Basal insulin, such as insulin glargine, can be initiated at a dose of 10 units at bedtime and adjusted by 2-4 units every 3-7 days based on fasting glucose levels 1.
• Lifestyle modifications, including dietary changes, regular physical activity, and glucose monitoring, are essential components of the treatment plan.
• The goal is to safely reduce blood glucose levels while minimizing the risk of hypoglycemia, with a target A1c of less than 7% for most patients.

Additional Therapy

• If glycemic targets are not met with metformin and basal insulin, a second agent such as a GLP-1 receptor agonist or mealtime insulin may be added to the treatment plan 1.
• The choice of additional therapy should be based on patient preferences, disease characteristics, and potential side effects 1.

Monitoring and Adjustment

• Blood glucose levels should be monitored regularly to adjust the treatment plan as needed.
• The dose of metformin and insulin should be adjusted based on glucose levels, and additional therapy should be considered if glycemic targets are not met.

From the FDA Drug Label

In a 26-week, dose-ranging study, 408 patients with type 2 diabetes were randomized to receive 7.5 mg, 15 mg, 30 mg, or 45 mg of ACTOS, or placebo once daily. Therapy with any previous antidiabetic agent was discontinued 8 weeks prior to the double-blind period. Treatment with 15 mg, 30 mg, and 45 mg of ACTOS produced statistically significant improvements in HbA1c and fasting plasma glucose (FPG) at endpoint compared to placebo.

For a patient with an A1c of 14.9, pioglitazone (PO) can be considered as a starting point for medication.

• The initial dose can be 15 mg or 30 mg once daily, as both doses have shown statistically significant improvements in HbA1c and FPG compared to placebo 2.
• It is essential to monitor the patient's response to the medication and adjust the dose as needed to achieve optimal glycemic control.
• Additionally, consideration should be given to combining pioglitazone with other antidiabetic agents, such as metformin or sulfonylurea, as combination therapy has been shown to have an additive effect on glycemic control 2.

From the Research

Medication for A1c of 14.9

• The American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus recommends an algorithm for glycemic control, which includes therapeutic pathways stratified on the basis of current levels of A1C 3.
• For a patient with an A1c of 14.9, the goal of therapy is to achieve a hemoglobin A1c (A1C) of 6.5% or less, with recognition of the need for individualization to minimize the risks of hypoglycemia 3.
• The algorithm prioritizes choices of medications according to safety, risk of hypoglycemia, efficacy, simplicity, anticipated degree of patient adherence, and cost of medications 3.
• Metformin is often considered a first-line treatment for type 2 diabetes, and its long-term effects have been shown to reduce diabetes incidence over 21 years 4.
• Other medication options may include sulfonylureas, meglitinides, thiazolidinediones, alpha-glucosidase inhibitors, and bile acid sequestrants, as well as insulin therapy 3.

Considerations for Medication Selection

• The choice of medication should be based on the patient's individual characteristics, such as renal function, hepatic function, and presence of other medical conditions 3.
• The patient's baseline HbA1c level can predict the likelihood of reaching a target HbA1c of 7.0% or less, with lower baseline HbA1c levels associated with a higher likelihood of achieving target 5.
• The risk of hypoglycemia should also be considered when selecting a medication, with lower baseline HbA1c levels associated with a higher risk of glucose-confirmed hypoglycaemia 5.

Monitoring and Adjusting Therapy

• Therapy should be monitored with A1C and self-monitoring of blood glucose, and adjusted or advanced frequently (every 2 to 3 months) if the appropriate goal for each patient has not been achieved 3.
• Continuous glucose monitoring (CGM) can also be used to monitor glycemia and adjust therapy, with improvements in psychosocial outcomes and HbA1c levels observed in patients using CGM 6.