Should the insulin regimen be adjusted in a patient with poorly controlled hyperglycemia, currently on 38 units of glargine (insulin glargine) qHS and 30 units of Novolog (insulin aspart) with meals, before increasing the dose of Actos (pioglitazone) from 15mg to 30mg?

From the Guidelines

I strongly recommend adjusting the insulin regimen before increasing the Actos dose to 30 mg from 15 mg. For a patient with difficult to control glucose and an average blood glucose of around 300 mg/dL, the current insulin doses of 38 units glargine qHS and 30 units Lipton with meals are likely inadequate. Consider increasing the basal insulin (glargine) to 45-50 units at bedtime and the mealtime insulin to 35-40 units with meals, as suggested by the 2017 American Diabetes Association standards of medical care in diabetes 1. This approach addresses the immediate need to lower blood glucose more effectively and can provide more rapid glucose control compared to increasing Actos, which may take weeks to reach full effect. Additionally, at higher doses, Actos (pioglitazone) carries increased risks of fluid retention, weight gain, and potential heart failure exacerbation. The insulin adjustment should be accompanied by frequent blood glucose monitoring, especially for hypoglycemia. Once better glucose control is established with optimized insulin, then consider the Actos dose increase if needed. This sequential approach allows you to assess the impact of each intervention separately and minimize the risk of hypoglycemia that might occur with simultaneous increases in both medications. Some key points to consider when adjusting the insulin regimen include:

• The importance of dose titration based on blood glucose levels and the pharmacodynamic profile of each insulin formulation 1
• The potential benefits of adding a single injection of rapid-acting insulin analogue before the largest meal, or adding a GLP-1–receptor agonist 1
• The need for frequent monitoring and potential adjustments to the insulin regimen to achieve optimal glucose control 1

From the FDA Drug Label

Insulin: ACTOS in combination with insulin may be initiated at 15 mg or 30 mg once daily. The current insulin dose can be continued upon initiation of ACTOS therapy In patients receiving ACTOS and insulin, the insulin dose can be decreased by 10% to 25% if the patient reports hypoglycemia or if plasma glucose concentrations decrease to less than 100 mg/dL.

The patient's insulin regimen should not be adjusted before increasing the Actos dose from 15 mg to 30 mg. According to the label, the current insulin dose can be continued upon initiation of ACTOS therapy. Adjustments to the insulin dose can be made later if the patient reports hypoglycemia or if plasma glucose concentrations decrease to less than 100 mg/dL, with decreases of 10% to 25% recommended 2.

From the Research

Insulin Regimen Adjustment

The patient's current insulin regimen consists of 38 units of glargine qHS and 30 units of Lipton with meals, with an average blood glucose (BG) level of around 300.

• The study 3 suggests that optimizing the insulin regimen, such as introducing an insulin analogue, can improve glycemic control in patients with Type 2 diabetes mellitus.
• However, this study does not provide direct guidance on adjusting the insulin regimen in response to increasing the dose of Actos (pioglitazone) from 15 mg to 30 mg.
• There is no direct evidence from the provided studies to support adjusting the insulin regimen before increasing the Actos dose.

Considerations for Adjusting Insulin Regimen

• The patient's high average BG level of 300 suggests that their current insulin regimen may not be adequate to achieve optimal glycemic control.
• Increasing the dose of Actos may improve insulin sensitivity, potentially leading to improved glycemic control.
• However, without direct evidence from the provided studies, it is unclear whether adjusting the insulin regimen before increasing the Actos dose is necessary or beneficial.

Lack of Direct Evidence

• The provided studies do not address the specific question of adjusting the insulin regimen in response to increasing the dose of Actos.
• Studies 4, 5, 6, and 7 are not relevant to the question of adjusting the insulin regimen in this context.
• Therefore, there is no clear evidence-based guidance on whether to adjust the insulin regimen before increasing the Actos dose.