What is the optimal medication regimen for a patient with type 2 diabetes mellitus (DM) currently taking Pioglitazone (Thiazolidinedione) 15 mg daily, Metformin (Biguanide) 500 mg twice daily, Glipizide (Sulfonylurea) 10 mg twice daily, and Humulin (Insulin) 18 units in the morning and 12 units in the afternoon, with Humulin R (Regular Insulin) sliding scale coverage?

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Last updated: April 25, 2025 • View editorial policy

From the Guidelines

For this patient with type 2 diabetes on multiple medications, I recommend simplifying the regimen by discontinuing pioglitazone and glipizide while continuing metformin and optimizing insulin therapy with Humulin for basal coverage and Humulin R for mealtime and correction doses. The patient is currently on a complex regimen including three oral agents (pioglitazone, metformin, and glipizide) plus basal insulin (Humulin) and correction insulin (Humulin R sliding scale), which represents medication redundancy and increases risk of hypoglycemia, as noted in the 2016 American Diabetes Association standards of medical care in diabetes 1. Key considerations for this patient include:

  • Metformin should be continued as first-line therapy due to its effectiveness, cardiovascular benefits, and low hypoglycemia risk, as recommended by the American Diabetes Association 1.
  • The insulin regimen should be optimized with Humulin for basal coverage, initiated at 10 units or 0.1 to 0.2 units/kg of body weight, and Humulin R for mealtime and correction doses, with timely dose titration based on self-monitoring of blood glucose (SMBG) levels 1.
  • Pioglitazone carries risks of fluid retention, heart failure exacerbation, and fractures, while glipizide (a sulfonylurea) increases hypoglycemia risk, especially when combined with insulin, making discontinuation of these medications a reasonable approach to reduce adverse effect risks. This simplified approach maintains glucose control through complementary mechanisms (metformin reducing hepatic glucose production and improving insulin sensitivity, while insulin provides both basal and mealtime coverage) while reducing medication burden and adverse effect risks, aligning with the American Diabetes Association's recommendations for diabetes management 1.

From the Research

Current Medication Regimen

The patient is currently taking:

  • Pioglitazone 15 mg a day
  • Metformin 500 mg twice daily
  • Glipizide 10 mg twice daily
  • Humulin 18 units in the morning and 12 units in the afternoon before lunch
  • Humulin R sliding scale coverage

Potential Medication Adjustments

Based on the studies, the following adjustments could be considered:

  • Continuing the fixed-dose combination of pioglitazone and metformin, as it has been shown to be effective in reducing cardiovascular morbidity and mortality 2
  • Discontinuing glipizide, as the combination of pioglitazone and metformin may be sufficient for glycemic control
  • Considering the addition of a GLP-1 receptor agonist or SGLT2 inhibitor to the patient's regimen, as combination therapy with these agents has been shown to have beneficial effects on glycemic control, body weight, and cardiovascular risk factors 3, 4, 5
  • Potentially discontinuing Humulin R sliding scale coverage, as the patient is already taking a basal insulin (Humulin) and the addition of a GLP-1 receptor agonist or SGLT2 inhibitor may reduce the need for sliding scale coverage

Benefits of Combination Therapy

The studies suggest that combination therapy with pioglitazone and a GLP-1 receptor agonist or SGLT2 inhibitor may have several benefits, including:

  • Improved glycemic control 5
  • Weight loss 5
  • Reduced risk of heart failure 5
  • Potential for improved cardiovascular outcomes 3, 4

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