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Diabetes Mellitus, Type 2Phase 4NCT06657209

Normal-weight Diabetes: Adipocyte-directed Therapy With Pioglitazone or Tirzepatide

A Phase 4 study testing Insulin resistance testing, OGTT and Fat biopsy in people with Diabetes Mellitus, Type 2 and Diabetes, run by Stanford University at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This study is to investigate how adipocyte (fat cell) function and fat distribution differ between individuals with normal-weight type 2 diabetes (NWD), those with overweight type 2 diabetes (OWD), and normal-weight controls without diabetes (NWC). Read more about this study

Who is it for?
Ages 30 to 70 yearsHealthy volunteers can take part
What is being tested?
Insulin resistance testing, OGTT and Fat biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
2 sitesUnited States
Study dates
13 Jan 2025to 15 Dec 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Normal-Weight Diabetes (NWD) Group:
  • Age: 30 to 70 years old.
  • Diagnosis of Type 2 Diabetes (T2D): Based on a previous diagnosis or confirmed by laboratory testing at screening (A1c > 5.7% or fasting glucose > 100 mg/dL).
  • HbA1c Range: Between 5.7% and 8%, with a stable medication or lifestyle regimen for at least 3 months.
  • BMI: Between 19 and 24.9 kg/m².
  • Diabetes Medications: All diabetes medications are allowed, except insulin and pioglitazone. GLP-1 receptor agonists are permitted if the dose has been stable for 3 months.
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  • Stable Body Weight: Body weight must have been stable (no more than 2 kg change) over the last 3 months.
  • Normal-Weight Control (NWC) Group:
  • Age: 30 to 70 years old.
  • No Diagnosis of Diabetes: Fasting plasma glucose < 100 mg/dL and A1c < 5.7%, with no history of glucose-lowering medications.
  • BMI: Between 19 and 24.9 kg/m².
  • Stable Body Weight: No more than 2 kg change over the past 3 months. -

Who cannot join

  • Pregnancy or Lactation: Women who are pregnant, planning to become pregnant, or breastfeeding are excluded due to potential risks to the fetus or infant.
  • Prior Use of Pioglitazone: Participants who have previously used pioglitazone are excluded to avoid confounding effects of prior drug exposure.
  • Unstable Body Weight: Individuals with a body weight change of more than 2 kg in the last 3 months are excluded to ensure stable metabolic conditions.
  • Liver or Kidney Disease: Participants with significant liver disease (ALT > 3x upper limit of normal) or renal disease (creatinine > 1.5 mg/dL) are excluded due to potential safety risks.
  • Congestive Heart Failure or Fluid Overload History: These conditions are exclusionary due to the risk of fluid retention with pioglitazone.
  • Uncontrolled Hypertension: Blood pressure > 160/90 mmHg excludes participants due to increased cardiovascular risk.
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  • Active Cancer: Individuals with a diagnosis of cancer in the past 3 years (except for skin cancer) are excluded.
  • Chronic Inflammatory Diseases: Excluded due to potential effects on metabolic measurements.
  • Use of Weight Loss Medications: Those currently taking weight loss medications are excluded to prevent confounding effects on body weight and metabolic function.
  • Bariatric Surgery or Liposuction History: Participants who have had weight-loss surgeries or liposuction are excluded due to alterations in fat tissue and metabolic profiles.
  • Insulin Use: Participants using insulin are excluded to focus on non-insulin-dependent diabetes.
  • Active Psychiatric Disease or Eating Disorders: Individuals with these conditions are excluded due to potential impacts on study compliance and data integrity.
  • Substance Abuse: Participants with a history of substance abuse are excluded for similar reasons.
  • -

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Nina Shenoy, BS contact

408-896-0134

nshenoy8@stanford.edu

Alisa Turner, BS contact

650-285-8855

alturner@stanford.edu

United States2 sites, 2 recruiting

  • Stanford University

    Palo Alto, California, 94304

    Nina Shenoy, BS, 408-896-0134, nshenoy8@stanford.edu

    Alisa Turner, BS, 650-285-8855, alturner@stanford.edu

    Recruiting

  • Stanford University, Clinical and Translational Research Unit (CTRU)

    Stanford, California, 94304

    Nina Shenoy, BS, 408-896-0134, nshenoy8@stanford.edu

    Alisa Turner, BS, 650-285-8855, alturner@stanford.edu

    Not yet recruiting

Other trials in United States

About this study

This study is to investigate how adipocyte (fat cell) function and fat distribution differ between individuals with normal-weight type 2 diabetes (NWD), those with overweight type 2 diabetes (OWD), and normal-weight controls without diabetes (NWC). The study will assess whether adipocyte-directed therapies, specifically pioglitazone and tirzepatide, can improve insulin resistance, adipocyte function, and fat distribution in individuals with NWD. By analyzing the biological mechanisms underlying adipocyte dysfunction, the study aims to provide insights into novel treatment strategies for improving metabolic health in normal-weight individuals with type 2 diabetes.

Read the detailed description

The investigators aim to learn how adipocyte dysfunction and disordered fat distribution contribute to the development of type 2 diabetes in normal-weight individuals. The investigators hope to determine whether adipocyte-directed therapies, such as pioglitazone and tirzepatide, can improve insulin sensitivity, fat distribution, and metabolic health in this population. This study is important because most diabetes research focuses on overweight or obese individuals, and very little is known about how diabetes affects those with normal body weight. Understanding the unique biology of normal-weight diabetes could lead to more personalized and effective treatment strategies, filling a gap in diabetes care for a group that can be overlooked in clinical research.

Being tested
Insulin resistance testing, OGTT, Fat biopsy, DXA scan, MRI
Keywords
metabolism, diabetes, pre-diabetes, insulin sensitivity, insulin resistance, insulin resistant, insulin sensitive, adipocyte
Medical subject headings
Diabetes Mellitus, Type 2, Diabetes Mellitus, Glucose Intolerance, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Insulin resistance testingProcedure or surgery

    Also called SSPG

    Steady state Plasma Glucose test

  • OGTTProcedure or surgery

    Also called Oral glucose tolerance test

    Will collect 5 blood draws during the test to measure insulin secretion

  • Fat biopsyProcedure or surgery

    Needle biopsy to gather a sample of abdominal subcutaneous fat

  • DXA scanRadiation

    Whole body DXA scan

  • MRIProcedure or surgery

    Abdominal MRI

  • 1H-MRSProcedure or surgery

    Also called proton magnetic resonance spectroscopy

    Spectroscopy of the abdominal region

  • TirzepatideDrug

    Also called Mounjaro

    16 weeks started at 2.5mg/week and increased to 5mg/week dose

  • PioglitazoneDrug

    Also called Actos

    16 weeks at a 45mg/day dose

Study groups in NCT06657209
Study groupRoleWhat they receive
Normal weight controlsOtherControl
Receives: Procedure: Insulin resistance testing; Procedure: OGTT; Procedure: Fat biopsy; Radiation: DXA scan; Procedure: MRI; Procedure: 1H-MRS
Normal weight with diabetes tirzepatide first pioglitazone secondExperimentalBaseline testing Intervention with tirzepatide for 16 weeks Retesting Washout for 5 weeks Intervention with pioglitazone for 16 weeks Retesting
Receives: Procedure: Insulin resistance testing; Procedure: OGTT; Procedure: Fat biopsy; Radiation: DXA scan; Procedure: MRI; Procedure: 1H-MRS; Drug: Tirzepatide; Drug: Pioglitazone
Normal weight with diabetes pioglitazone first, tirzepatide secondExperimentalBaseline testing Intervention with pioglitazone for 16 weeks Retesting Washout for 5 weeks Intervention with tirzepatide for 16 weeks Retesting
Receives: Procedure: Insulin resistance testing; Procedure: OGTT; Procedure: Fat biopsy; Radiation: DXA scan; Procedure: MRI; Procedure: 1H-MRS; Drug: Tirzepatide; Drug: Pioglitazone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Insulin resistance in normal weight women with diabetes compared to those with no diabetes

    Insulin resistance will be measured by a Steady State Plasma Glucose test (SSPG). Results will be measured by glucose levels at steady state in mg/dL.

    Measured: Baseline measures comparison between the groups

  2. Adipocyte function in women with normal weight diabetes as compared with those without diabetes

    Adipocyte function will be measured as percent small adipocytes and peak diameter adipocytes from the fat biopsies.

    Measured: Baseline comparisons

  3. Fat storage in women with normal weight diabetes compared to those without diabetes

    Fat storage will be measured by MRI. Quantification of subcutaneous and visceral abdominal fat will be obtained by MRI using a fat-water imaging sequence (parameters: IDEAL-IQ: 3D GRE, 160x160 matrix, 6 echoes, 4 degree flip angle, minimum TR = 7.3 ms, 28 slices, 10 mm slice thickness.

    Measured: Baseline comparisons between the groups

Secondary outcomes (6)

  1. Effect of adipose-directed therapy pioglitazone on HbA1c in both men and women with normal weight diabetes

    Hemoglobin A1C measures will be compared baseline to end of 16 weeks of intervention with pioglitazone.

    Measured: 16 weeks

  2. Effect of pioglitazone in insulin resistance in both men and women.

    SSPG test results will be compared from baseline to end of pioglitazone intervention.

    Results will be measured by glucose levels at steady state in mg/dL.

    Measured: 16 weeks

  3. Fat storage in men with normal weight diabetes (NWD) compared to those without diabetes (NWC).

    Fat storage will be measured by MRI. Quantification of subcutaneous and visceral abdominal fat will be obtained by MRI using a fat-water imaging sequence (parameters: IDEAL-IQ: 3D GRE, 160x160 matrix, 6 echoes, 4 degree flip angle, minimum TR = 7.3 ms, 28 slices, 10 mm slice thickness.

    Measured: Baseline comparisons between the groups

  4. Adipocyte function in men with normal weight diabetes as compared with those without diabetes

    Adipocyte function as measured by percent small adipocytes and peak diameter adipocytes from the fat biopsies.

    Measured: Baseline comparisons

  5. Insulin resistance in normal weight men with diabetes compared to those with no diabetes

    Insulin resistance will be measured by a Steady State Plasma Glucose test (SSPG). Results will be measured by glucose levels at steady state in mg/dL.

    Measured: Baseline measures comparison between the groups

  6. Insulin secretion in men and women with normal weight diabetes compared to those without diabetes

    A five-point, three-hour OGTT will be done after overnight fast for calculation of insulin secretion using c-peptide deconvolution, and disposition index calculated by dividing this value by SSPG.

    Measured: Baseline measured compared between the groups

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Oct 2024
  2. Study start13 Jan 2025
  3. Primary completion15 Dec 2027 (estimated)
  4. Study completion15 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
Control groups will undergo baseline testing to provide information about people without diabetes, but will not proceed with treatment.
Masking
None (open label)
Enrolment
104 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06657209
Sponsor's protocol ID
77199
Status last verified
Apr 2026
First submitted
18 Oct 2024
Last updated
20 Apr 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Insulin resistance testing, OGTT and Fat biopsy in people with Diabetes Mellitus, Type 2 and Diabetes, run by Stanford University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 20 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Nina Shenoy, BS (408-896-0134, nshenoy8@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Insulin resistance in normal weight women with diabetes compared to those with no diabetes (time frame: Baseline measures comparison between the groups). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06657209.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2026.

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