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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how pioglitazone, a drug typically used for type 2 diabetes, affects fat metabolism in individuals with upper body obesity. Researchers aim to determine if this drug can enhance the body's management and use of fat, particularly when the usual insulin response is impaired. Participants will receive either pioglitazone or a placebo (a pill with no active drug) as part of a broader lifestyle program targeting weight loss. The trial seeks men and premenopausal women with a BMI between 30 and 38 who have noticeable upper body weight gain. As an Early Phase 1 trial, this research focuses on understanding how pioglitazone functions in people with upper body obesity.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pioglitazone, a drug commonly used for type 2 diabetes, is generally safe but can have some side effects. Studies have found that while it helps lower blood sugar and fat levels in the blood, it often leads to weight gain. This weight gain can result from fluid retention or extra body fat. Some people might also experience swelling due to excess fluid, known as edema.

Despite these side effects, pioglitazone remains safe for use. When considering participation in a trial, it is important to weigh these potential side effects against the benefits. Those concerned about weight gain or swelling should discuss these issues with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Pioglitazone is unique because it targets obesity by potentially influencing fat distribution and insulin sensitivity, both critical factors in managing weight. Most current treatments for obesity focus on diet, exercise, and sometimes medications that suppress appetite or block fat absorption. Pioglitazone, however, is an insulin sensitizer commonly used for type 2 diabetes, which may help manage fat storage and improve metabolic health in obese individuals. Researchers are excited because it offers a different approach by possibly addressing the root metabolic issues rather than just the symptoms of obesity.

What evidence suggests that this trial's treatments could be effective for obesity?

Research has shown that pioglitazone, a drug typically used for type 2 diabetes, improves the body's insulin use, enhancing insulin effectiveness. In this trial, some participants will receive pioglitazone, while others will receive a placebo. Although some individuals may gain weight with pioglitazone, it also lowers blood sugar and triglycerides. These effects could assist individuals with obesity in managing their weight by improving fat metabolism. However, users should be aware that pioglitazone might cause mild swelling in some cases. ^{1 6 7 8 9}

Who Is on the Research Team?

Michael D Jensen

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4406881/

The effect of pioglitazone on weight, lipid profile and liver ... Although pioglitazone causes a significant decrease in FBS, HbA1C and triglyceride levels, it is associated with weight gain, which would limit its utility.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291800800788

A systematic review of the clinical effectiveness ... Pioglitazone treatment was associated with significant weight gain (up to 4 kg over 16 weeks). Adverse effects included mild edema (in up to 11.7% of patients) ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11911819/

Comparing Pioglitazone/Metformin with Dapagliflozin Versus ... Patients in the test group whose BMI≥24 kg/m2 also achieved a substantial achievement rate (36.73% vs 15.79%, P=0.014). The test group also ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/021842s014s015lbl.pdf

ACTOPLUS MET - accessdata.fda.gov Pioglitazone hydrochloride The following drugs were studied in healthy volunteers with co-administration of pioglitazone 45 mg once daily. Results are listed ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014299911008223

Pioglitazone-induced body weight gain is prevented by ... After 7 weeks of drug treatment, pioglitazone + NO-1886 was found to prevent the body weight gain caused by pioglitazone alone (pioglitazone + NO-1886: Δ76.0 ± ...

6. dmsjournal.biomedcentral.com dmsjournal.biomedcentral.com/articles/10.1186/s13098-017-0290-5

Effects of pioglitazone therapy on blood parameters, weight ... Pioglitazone has a manageable safety profile but remains associated with weight gain and edema [35]. Nevertheless, pioglitazone is not the drug ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S014929182400198X

Efficacy and Safety of Pioglitazone Add-on in Patients with ... Treatment with PIO resulted in significant weight gain compared with that induced by PBO (2.02 kg [95% CI, 1.49 to 2.54] and 2.61 kg [95% CI, 2.01 to 3.20], ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00772174?tab=table

Efficacy and Safety Study of Pioglitazone Combined With ... The metabolic syndrome is a cluster of the most dangerous cardiovascular risk factors and includes diabetes and pre-diabetes in addition to abdominal obesity, ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/022024s007s008lbl.pdf

actoplus met - accessdata.fda.gov Pioglitazone, one of the medicines in ACTOPLUS MET XR, can cause weight gain that may be due to fluid retention or extra body fat. Weight gain due to fluid ...