Therapy for Patients with Inadequate Glycemic Control

Introduction to Therapy

Pioglitazone is a medication that improves glucose metabolism and lipid profiles, and may reverse non-alcoholic steatohepatitis and improve fibrosis in patients with type 2 diabetes and NASH, as indicated by the American Diabetes Association and the International Diabetes Federation 1, 2, 1

Patients with non-alcoholic steatohepatitis (NASH) may benefit from therapy, as it can reverse steatohepatitis in patients with and without diabetes, according to the American Diabetes Association and the American Association for the Study of Liver Diseases 3, 2
Patients with a history of stroke or transient ischemic attack (TIA) may benefit from therapy, as it may reduce the risk of recurrent stroke, as recommended by the American Heart Association and the European Association for the Study of Diabetes 4, 5, 6

Therapy may reduce the risk of stroke or myocardial infarction in patients with a history of stroke and insulin resistance, with a 47% relative risk reduction in recurrent stroke among patients with a history of stroke, as reported by the European Association for the Study of Diabetes and the American Stroke Association 5, 4
The PROactive trial found that pioglitazone was associated with a reduction in cardiovascular events, according to the American Stroke Association 4

Therapy can reverse steatohepatitis in patients with NASH, with a resolution rate of 47% compared to 21% in the placebo group, as shown in the PIVENS trial and reported by the American Association for the Study of Liver Diseases 3
Therapy may slow fibrosis progression in patients with NASH, as recommended by the American Gastroenterological Association and the American Heart Association 2, 1

Benefits on NASH may require at least 18 months of treatment, according to the American Diabetes Association 2
Long-term therapy is typically required for sustained glycemic control, although the exact duration is not specified, as indicated by the American Diabetes Association and the International Diabetes Federation 3, 2, 1

The initial dose of pioglitazone is typically 15 mg once daily, with a maximum approved daily dose of 45 mg, and can be titrated based on glycemic response, typically after 8-12 weeks of treatment if adequate glycemic control is not achieved, as recommended by the American Association of Clinical Endocrinologists 7, 8, 9
The American Association of Clinical Endocrinologists recommends considering lower doses (7.5-15 mg) in high-risk patients, as they may provide similar glycemic benefits with fewer side effects 8

Patients on pioglitazone should be monitored for signs of fluid retention and edema, especially when combined with insulin, as the risk of edema increases with combination therapy, according to the American Heart Association and the American College of Cardiology 8, 9
Regular assessment for weight gain, edema, and signs of heart failure is essential, particularly when using higher doses or in combination with insulin, as recommended by the American Heart Association and the American College of Cardiology 8, 9
Common side effects include weight gain (average 0.9-2.6 kg at doses of 15-45 mg daily) and edema/fluid retention, which is more common at higher doses, particularly when combined with insulin, according to the American Heart Association and the American College of Cardiology 8, 9

Patients with class III-IV heart failure according to the NYHA classification should not be treated with pioglitazone due to increased risk of cardiovascular events, as recommended by the American Heart Association and the American College of Cardiology 8, 9
The American College of Cardiology recommends considering the risk of fractures, especially in women, when prescribing pioglitazone, and avoiding pioglitazone in patients with NYHA Class III or IV heart failure 8, 9
Patients with pre-existing cardiovascular disease are at increased risk of heart failure when taking pioglitazone, according to the American Heart Association and the American College of Cardiology 8, 9