Is Pioglitazone (thiazolidinedione) 30 mg suitable for uncontrolled Diabetes Mellitus (DM)?

From the Guidelines

Pioglitazone 30 mg can be a suitable option for uncontrolled diabetes mellitus, particularly for type 2 diabetes patients who haven't achieved adequate glycemic control with other medications, as it has a high glucose-lowering efficacy with a low risk of hypoglycemia 1. This thiazolidinedione works by increasing insulin sensitivity in peripheral tissues and reducing hepatic glucose production, making it effective for lowering blood glucose levels. The typical starting dose is 15-30 mg once daily, which can be increased to a maximum of 45 mg daily if needed. Pioglitazone should be taken with or without food and requires several weeks (usually 8-12 weeks) to reach maximum effectiveness. Some key considerations for its use include:

• Potential side effects: weight gain, fluid retention, and increased risk of heart failure, making it unsuitable for those with existing heart failure (NYHA Class III or IV) 1.
• Increased risk of bone fractures, particularly in women 1.
• Regular monitoring of liver function is recommended, especially during the first year of treatment 1.
• Pioglitazone is often used as part of combination therapy with metformin, sulfonylureas, or insulin when these medications alone don't provide adequate control 1. It's also important to consider the patient's overall health status, including the presence of any comorbidities such as chronic kidney disease, as this may influence the choice of glucose-lowering therapy 1. Overall, pioglitazone can be a valuable addition to the treatment regimen for patients with uncontrolled type 2 diabetes, but its use should be carefully considered and monitored to minimize potential risks.

From the FDA Drug Label

In a 16-week monotherapy trial, 197 patients with type 2 diabetes were randomized to treatment with 30 mg of pioglitazone hydrochloride or placebo once daily. Therapy with any previous antidiabetic agent was discontinued six weeks prior to the double-blind period Treatment with 30 mg of pioglitazone hydrochloride produced statistically significant improvements in HbA1c and FPG at endpoint compared to placebo

Table 19. Glycemic Parameters in a 16-Week Placebo-Controlled Monotherapy Trial Placebo Pioglitazone Hydrochloride 30 mg Once Daily *Adjusted for baseline, pooled center, and pooled center by treatment interaction†p ≤ 0. 050 vs. placebo Total Population HbA1c (%) N=93 N=100 Baseline (mean) 10.3 10.5 Change from baseline (adjusted mean *) 0.8 -0.6 Difference from placebo (adjusted mean *) 95% Confidence Interval -1.4 † (-1.8, -0. 9) Fasting Plasma Glucose (mg/dL) N=91 N=99 Baseline (mean) 270 273 Change from baseline (adjusted mean *) 8 -50 Difference from placebo (adjusted mean *) 95% Confidence Interval -58 † (-77, -38)

Pioglitazone 30 mg is suitable for uncontrolled Diabetes Mellitus (DM), as it has been shown to produce statistically significant improvements in HbA1c and FPG at endpoint compared to placebo in clinical trials 2.

• Key benefits of Pioglitazone 30 mg include:
  • Improved glycemic control
  • Statistically significant reductions in HbA1c and FPG
• Clinical trials have demonstrated the efficacy of Pioglitazone 30 mg in patients with type 2 diabetes, including those with uncontrolled DM.

From the Research

Suitability of Pioglitazone 30 mg for Uncontrolled Diabetes Mellitus (DM)

• Pioglitazone is an antidiabetic drug that targets insulin resistance in patients with type 2 diabetes mellitus by stimulating the peroxisome proliferator-activated receptor (PPAR)-gamma 3.
• The most frequent starting daily dose of pioglitazone was either 15 mg or 30 mg, with pioglitazone 30 mg being effective in reducing mean HbA(1c) by 0.8% from baseline 4.
• Pioglitazone 30 mg was also effective in reducing fasting serum insulin and increasing insulin sensitivity, as well as improving lipid profiles 4.
• In patients with newly diagnosed uncontrolled type 2 diabetes mellitus, pioglitazone 30 mg monotherapy was equally effective as gliclazide and metformin in achieving glycemic control, but showed more pronounced improvements in cardiovascular risk factors 5.
• Pioglitazone was considered to be a reasonably well-tolerated drug, with the main reasons for discontinuing being related to the drug not being effective, and the frequency of individual adverse drug reactions did not exceed the frequency in the summary of product characteristics (SPC) for pioglitazone 3.

Efficacy and Safety of Pioglitazone 30 mg

• Pioglitazone 30 mg was effective in reducing plasma glucose and HbA1c from baseline levels in patients with type 2 diabetes mellitus on hemodialysis 6.
• The agent was also effective in reducing triglycerides and improving insulin resistance in these patients 6.
• No serious adverse effects were observed in patients treated with pioglitazone 30 mg, and the drug was well-tolerated 4, 6.
• Pioglitazone 30 mg may have the potential to reduce the number of type 2 diabetics on hemodialysis who ultimately require insulin injection therapy 6.

Comparison with Other Treatments

• Pioglitazone 30 mg monotherapy was compared to gliclazide and metformin monotherapies in patients with newly diagnosed uncontrolled type 2 diabetes mellitus, and was found to be equally effective in achieving glycemic control 5.
• However, pioglitazone 30 mg showed more pronounced improvements in cardiovascular risk factors, such as reductions in triglycerides, vWF, IL-6, ICAM-1, E-selectin, and Hcy, and an increase in HDL-C 5.