Pioglitazone for Obesity

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Mayo Clinic

Must be taking: Pioglitazone

Disqualifiers: Heart failure, Hypersensitivity, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

64 Participants Needed

Trial Summary

What is the purpose of this trial?

These studies will define the abnormalities in the adipocyte proteins that are involved in the failure of insulin to suppress lipolysis normally in humans with upper body obesity and will help discover the mechanism by which pioglitazone, a medication used to treat type 2 diabetes and improve insulin resistance, improves insulin-regulation of adipocyte fatty acid metabolism.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Pioglitazone for obesity?

While there is no direct evidence from the provided research about Pioglitazone's effectiveness for obesity, it is known to improve insulin sensitivity and reduce cardiovascular risk in patients with type 2 diabetes, which might indirectly suggest potential benefits for weight management. ^{1 2 3 4 5}

Is pioglitazone safe for humans?

Pioglitazone has been generally well tolerated in clinical trials, with common side effects including weight gain and swelling. However, it has been associated with an increased risk of bladder cancer, heart failure, and bone fractures in postmenopausal women. It is important to weigh these risks against the benefits when considering its use. ^{1 6 7 8 9}

How does the drug pioglitazone differ from other treatments for obesity?

Pioglitazone is unique because it is primarily used to treat type 2 diabetes by improving insulin sensitivity, which may indirectly affect weight. Unlike other obesity treatments, it works by altering gene expression to reduce insulin resistance, potentially offering a novel approach to managing obesity. ^{1 3 10 11 12}

Research Team

Michael D Jensen

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for men and women aged 18-55, including premenopausal women. It's suitable for non-obese adults with a BMI of 18-25 and obese individuals with a BMI of 30-38. People allergic to pioglitazone or with severe heart failure (NYHA class III/IV) cannot participate.

Inclusion Criteria

Obese BMI 30-38

My BMI is between 18 and 25, so I am not obese.

I am a woman and have not gone through menopause.

Exclusion Criteria

Use in patients with known hypersensitivity to pioglitazone or any other component of ACTOSE.

I have severe heart failure (NYHA class III or IV).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Studies

Participants undergo baseline studies to assess initial conditions and measurements

2 weeks

Deferred Control Group - Placebo

Participants wait without any intervention for 4 months, with continued monitoring to assure weight stability

4 months

Immediate Weight Loss - Placebo

Participants begin immediate participation in a comprehensive lifestyle obesity treatment program

4 months

Deferred Group - Pioglitazone

Participants wait without any intervention for 4 months, monitored to prevent weight gain, while on pioglitazone

4 months

Immediate Weight Loss - Pioglitazone

Participants begin immediate participation in a comprehensive lifestyle obesity treatment program with pioglitazone

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-9 months

Treatment Details

Interventions

• Deferred weight loss
• Immediate weight loss
• Pioglitazone
• Placebo

Trial Overview The study investigates how the drug Pioglitazone affects fat cell metabolism in those with upper body obesity. It compares immediate weight loss strategies, deferred weight loss plans, and placebo effects on insulin's ability to control fat breakdown.

Participant Groups

Group I: Immediate weight loss - placebo Active Control 2 Interventions

Upper body obese participants randomized to this group; all will begin their immediate participation in a comprehensive lifestyle obesity treatment program after completion of baseline studies. Half of the volunteers will be randomized to placebo during this period.

Group II: Deferred group - pioglitazone Active Control 2 Interventions

After baseline studies, UBO participants randomized to this group will wait without any intervention for 4 months, with continued monitoring to assure weight stability - this group will be the half of volunteers randomized to deferred weight loss intervention that are randomized to pioglitazone. They will be monitored to prevent the usual but modest weight gain associated with pioglitazone. They will be on pioglitazone during the 'wait' period. At the end of this 'wait' period they will be enrolled in the same comprehensive lifestyle obesity treatment program for 4 months, but without pioglitazone.

Group III: Immediate weight loss - pioglitazone Active Control 2 Interventions

Upper body obese participants randomized to this group; all will begin their immediate participation in a comprehensive lifestyle obesity treatment program after completion of baseline studies. Half of the volunteers will be randomized to pioglitazone during this period.

Group IV: Deferred control group - placebo Placebo Group 2 Interventions

After baseline studies, UBO participants randomized to this group will wait without any intervention for 4 months, with continued monitoring to assure weight stability - this group will be the half of volunteers randomized to deferred weight loss intervention that are also randomized to placebo. At the end of this 'wait' period they will be enrolled in the same comprehensive lifestyle obesity treatment program for 4 months, but without placebo.

Pioglitazone is already approved in United States for the following indications:

Approved in United States as Actos for:

• Type 2 diabetes mellitus

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Pioglitazone effectively increases insulin sensitivity and improves glycemic control in patients with type 2 diabetes, whether used alone or in combination with other medications, based on clinical trials.

The medication is generally well tolerated, with weight gain and edema being the most common side effects, and it also shows potential benefits in reducing cardiovascular risk and arteriosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on pioglitazone in type 2 diabetes mellitus. Waugh, J., Keating, GM., Plosker, GL., et al.[2019]

Pioglitazone effectively reduces glycosylated hemoglobin (HbA1c) levels in patients with type 2 diabetes, showing similar efficacy in both younger (<65 years) and older (≥65 years) age groups, with reductions of 0.53-1.27% observed in monotherapy studies.

The addition of pioglitazone to other diabetes medications (sulfonylureas, metformin, or insulin) also resulted in significant HbA1c reductions, with no major differences in effectiveness or adverse events between age groups, although hypoglycemia rates varied depending on the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pioglitazone is effective therapy for elderly patients with type 2 diabetes mellitus. Rajagopalan, R., Perez, A., Ye, Z., et al.[2022]

In a study of 186 patients switched from troglitazone to either pioglitazone or rosiglitazone, both groups showed no significant change in glycemic control (HbA1c levels) after 4 months, indicating similar efficacy in managing blood sugar levels.

However, the pioglitazone group experienced a significant improvement in lipid profiles, with an average decrease in total cholesterol of about 20 mg/dl, while the rosiglitazone group showed no such improvement, highlighting a potential advantage of pioglitazone in lipid management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone. Khan, MA., St Peter, JV., Xue, JL.[2022]

Adding pioglitazone to insulin regimens in patients with type 2 diabetes leads to a significant reduction in HbA1c levels by an average of 0.58%, indicating improved blood sugar control.

However, this benefit comes with increased risks of hypoglycaemia and weight gain, with patients on pioglitazone gaining nearly 3 kg on average, highlighting the need for careful consideration of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding pioglitazone to insulin containing regimens in type 2 diabetes: systematic review and meta-analysis. Clar, C., Royle, P., Waugh, N.[2021]

In a 16-week study involving 328 patients with poorly controlled type 2 diabetes, the combination of pioglitazone and metformin significantly reduced HbA1c levels by an average of -0.83% and fasting plasma glucose by -37.7 mg/dL compared to placebo, indicating improved blood sugar control.

The combination treatment also positively affected lipid profiles, reducing triglycerides by -18.2% and increasing HDL cholesterol by +8.7%, with no evidence of liver damage throughout the study, suggesting a safe long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study. The Pioglitazone 027 Study Group. Einhorn, D., Rendell, M., Rosenzweig, J., et al.[2022]

Pioglitazone has been evaluated for safety in over 5,400 subjects, with more than 3,500 receiving the drug, resulting in over 2,500 patient-years of exposure, indicating a robust safety profile.

The trials demonstrated that pioglitazone is well-tolerated both as a standalone treatment and in combination with other diabetes medications, with comprehensive monitoring of adverse events and health metrics throughout the studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of pioglitazone. Hanefeld, M., Belcher, G.[2022]

Pioglitazone, approved in 1999 for type 2 diabetes, not only improves glycemic control by reducing insulin resistance but also positively affects lipid metabolism, blood pressure, and inflammation markers, making it beneficial beyond just glucose management.

Despite concerns about potential cancer risks associated with pioglitazone, it is generally considered a safer option among thiazolidinedione-class drugs, and its continued use is recommended for patients who can benefit from its multiple effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pioglitazone: Indian perspective. Shukla, R., Kalra, S.[2021]

Insulin-dependent oral antidiabetic agents like metformin, sulfonylureas, and gliptins are generally safe but have limitations in maintaining long-term blood glucose control, with no single drug providing stable control for years.

Metformin can cause gastrointestinal discomfort, while sulfonylureas carry risks of hypoglycemia and weight gain; additionally, pioglitazone is linked to serious side effects such as bladder cancer and heart failure, highlighting the need for careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Limitations of insulin-dependent drugs in the treatment of type 2 diabetes mellitus]. Valerón, PF., de Pablos-Velasco, PL.[2018]

In a study of 2396 patients, vildagliptin and pioglitazone/rosiglitazone showed similar overall adverse drug events, indicating that both medications are comparably safe for treating Type 2 Diabetes Mellitus (T2DM).

However, pioglitazone/rosiglitazone was associated with significantly lower dizziness compared to vildagliptin, while rosiglitazone specifically led to higher rates of weight gain and peripheral edema, suggesting the need for further investigation into these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug effects observed with vildagliptin versus pioglitazone or rosiglitazone in the treatment of patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Bundhun, PK., Janoo, G., Teeluck, AR., et al.[2018]

In a study involving 85 type 2 diabetic patients, both generic (Utmos) and original (Actos) 30 mg Pioglitazone tablets effectively reduced HbA1c and fasting plasma glucose levels without significant differences in efficacy between the two formulations.

Both medications showed similar safety profiles, with comparable rates of side effects like headache and edema, indicating that the generic version is a safe and effective alternative to the original.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of generic and original pioglitazone in type 2 diabetes mellitus: a multicenter, a double-blinded, randomized-controlled study. Rawdaree, P., Deerochanawong, C., Peerapatdit, T., et al.[2022]

A study assessing a new 45 mg formulation of pioglitazone found it to be bioequivalent to the reference product, meeting European regulatory standards for both absorption rate and extent, based on a trial with healthy volunteers.

Both the new and reference formulations were well tolerated, indicating safety in the tested population, and the study confirmed the applicability of using truncated AUC methods for evaluating bioequivalence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Truncated areas under the curve in the assessment of pioglitazone bioequivalence. Data from a single-center, single-dose, randomized, open-label, 2-way cross-over bioequivalence study of two formulations of pioglitazone 45 mg tablets under fasting conditions. Almeida, S., Filipe, A., Neves, R., et al.[2018]

Pioglitazone effectively reduces insulin resistance in over 4500 patients with type 2 diabetes, showing significant decreases in HbA1c levels and improvements in lipid profiles, whether used alone or in combination with other diabetes medications.

It is well tolerated with a low incidence of side effects and does not carry the risk of hepatotoxicity associated with a similar drug, troglitazone, making it a safer option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pioglitazone. Lawrence, JM., Reckless, JP.[2018]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on pioglitazone in type 2 diabetes mellitus. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Pioglitazone is effective therapy for elderly patients with type 2 diabetes mellitus. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Adding pioglitazone to insulin containing regimens in type 2 diabetes: systematic review and meta-analysis. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study. The Pioglitazone 027 Study Group. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety profile of pioglitazone. [2022]

7. India pubmed.ncbi.nlm.nih.gov

Pioglitazone: Indian perspective. [2021]

8. Spain pubmed.ncbi.nlm.nih.gov

[Limitations of insulin-dependent drugs in the treatment of type 2 diabetes mellitus]. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Adverse drug effects observed with vildagliptin versus pioglitazone or rosiglitazone in the treatment of patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. [2018]

10. Thailand pubmed.ncbi.nlm.nih.gov

Efficacy and safety of generic and original pioglitazone in type 2 diabetes mellitus: a multicenter, a double-blinded, randomized-controlled study. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Truncated areas under the curve in the assessment of pioglitazone bioequivalence. Data from a single-center, single-dose, randomized, open-label, 2-way cross-over bioequivalence study of two formulations of pioglitazone 45 mg tablets under fasting conditions. [2018]

12. India pubmed.ncbi.nlm.nih.gov

Pioglitazone. [2018]