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

April 15, 2026 updated by: Tracey McLaughlin, Stanford University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
104

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
      • Stanford, California, United States, 94304
        • Not yet recruiting
        • Stanford University, Clinical and Translational Research Unit (CTRU)
        • Principal Investigator:
          • Tracey McLaughlin, MD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Normal-Weight Diabetes (NWD) Group:

  1. Age: 30 to 70 years old.
  2. 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).
  3. HbA1c Range: Between 5.7% and 8%, with a stable medication or lifestyle regimen for at least 3 months.
  4. BMI: Between 19 and 24.9 kg/m².
  5. 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.
  6. 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:

  1. Age: 30 to 70 years old.
  2. No Diagnosis of Diabetes: Fasting plasma glucose < 100 mg/dL and A1c < 5.7%, with no history of glucose-lowering medications.
  3. BMI: Between 19 and 24.9 kg/m².
  4. Stable Body Weight: No more than 2 kg change over the past 3 months. -

Exclusion Criteria:

  1. Pregnancy or Lactation: Women who are pregnant, planning to become pregnant, or breastfeeding are excluded due to potential risks to the fetus or infant.
  2. Prior Use of Pioglitazone: Participants who have previously used pioglitazone are excluded to avoid confounding effects of prior drug exposure.
  3. 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.
  4. 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.
  5. Congestive Heart Failure or Fluid Overload History: These conditions are exclusionary due to the risk of fluid retention with pioglitazone.
  6. Uncontrolled Hypertension: Blood pressure > 160/90 mmHg excludes participants due to increased cardiovascular risk.
  7. Active Cancer: Individuals with a diagnosis of cancer in the past 3 years (except for skin cancer) are excluded.
  8. Chronic Inflammatory Diseases: Excluded due to potential effects on metabolic measurements.
  9. Use of Weight Loss Medications: Those currently taking weight loss medications are excluded to prevent confounding effects on body weight and metabolic function.
  10. 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.
  11. Insulin Use: Participants using insulin are excluded to focus on non-insulin-dependent diabetes.
  12. Active Psychiatric Disease or Eating Disorders: Individuals with these conditions are excluded due to potential impacts on study compliance and data integrity.

  13. Substance Abuse: Participants with a history of substance abuse are excluded for similar reasons.

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Normal weight controls
Control
Procedure: Insulin resistance testing
Steady state Plasma Glucose test
Other Names:
  • SSPG
Procedure: OGTT
Will collect 5 blood draws during the test to measure insulin secretion
Other Names:
  • Oral glucose tolerance test
Procedure: Fat biopsy
Needle biopsy to gather a sample of abdominal subcutaneous fat
Radiation: DXA scan
Whole body DXA scan
Procedure: MRI
Abdominal MRI
Procedure: 1H-MRS
Spectroscopy of the abdominal region
Other Names:
  • proton magnetic resonance spectroscopy
Experimental: Normal weight with diabetes tirzepatide first pioglitazone second
Baseline testing Intervention with tirzepatide for 16 weeks Retesting Washout for 5 weeks Intervention with pioglitazone for 16 weeks Retesting
Procedure: Insulin resistance testing
Steady state Plasma Glucose test
Other Names:
  • SSPG
Procedure: OGTT
Will collect 5 blood draws during the test to measure insulin secretion
Other Names:
  • Oral glucose tolerance test
Procedure: Fat biopsy
Needle biopsy to gather a sample of abdominal subcutaneous fat
Radiation: DXA scan
Whole body DXA scan
Procedure: MRI
Abdominal MRI
Procedure: 1H-MRS
Spectroscopy of the abdominal region
Other Names:
  • proton magnetic resonance spectroscopy
Drug: Tirzepatide
16 weeks started at 2.5mg/week and increased to 5mg/week dose
Other Names:
  • Mounjaro
Drug: Pioglitazone
16 weeks at a 45mg/day dose
Other Names:
  • Actos
Experimental: Normal weight with diabetes pioglitazone first, tirzepatide second
Baseline testing Intervention with pioglitazone for 16 weeks Retesting Washout for 5 weeks Intervention with tirzepatide for 16 weeks Retesting
Procedure: Insulin resistance testing
Steady state Plasma Glucose test
Other Names:
  • SSPG
Procedure: OGTT
Will collect 5 blood draws during the test to measure insulin secretion
Other Names:
  • Oral glucose tolerance test
Procedure: Fat biopsy
Needle biopsy to gather a sample of abdominal subcutaneous fat
Radiation: DXA scan
Whole body DXA scan
Procedure: MRI
Abdominal MRI
Procedure: 1H-MRS
Spectroscopy of the abdominal region
Other Names:
  • proton magnetic resonance spectroscopy
Drug: Tirzepatide
16 weeks started at 2.5mg/week and increased to 5mg/week dose
Other Names:
  • Mounjaro
Drug: Pioglitazone
16 weeks at a 45mg/day dose
Other Names:
  • Actos

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Insulin resistance in normal weight women with diabetes compared to those with no diabetes
Time Frame: Baseline measures comparison between the groups
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.
Baseline measures comparison between the groups
Adipocyte function in women with normal weight diabetes as compared with those without diabetes
Time Frame: Baseline comparisons
Adipocyte function will be measured as percent small adipocytes and peak diameter adipocytes from the fat biopsies.
Baseline comparisons
Fat storage in women with normal weight diabetes compared to those without diabetes
Time Frame: Baseline comparisons between the groups
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.
Baseline comparisons between the groups

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Effect of adipose-directed therapy pioglitazone on HbA1c in both men and women with normal weight diabetes
Time Frame: 16 weeks
Hemoglobin A1C measures will be compared baseline to end of 16 weeks of intervention with pioglitazone.
16 weeks
Effect of pioglitazone in insulin resistance in both men and women.
Time Frame: 16 weeks

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.
16 weeks
Fat storage in men with normal weight diabetes (NWD) compared to those without diabetes (NWC).
Time Frame: Baseline comparisons between the groups
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.
Baseline comparisons between the groups
Adipocyte function in men with normal weight diabetes as compared with those without diabetes
Time Frame: Baseline comparisons
Adipocyte function as measured by percent small adipocytes and peak diameter adipocytes from the fat biopsies.
Baseline comparisons
Insulin resistance in normal weight men with diabetes compared to those with no diabetes
Time Frame: Baseline measures comparison between the groups
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.
Baseline measures comparison between the groups
Insulin secretion in men and women with normal weight diabetes compared to those without diabetes
Time Frame: Baseline measured compared between the groups
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.
Baseline measured compared between the groups

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Effect of adipose-directed therapy with tirzepatide on insulin resistance in men and women with normal weight diabetes (NWD).
Time Frame: 16 weeks
SSPG test results will be compared from baseline to end of tirzepatide intervention. Results will be measured by glucose levels at steady state in mg/dL.
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Stanford University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 13, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 15, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 15, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 18, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 22, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 24, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 20, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 15, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 77199

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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