Fat‑targeted treatment with pioglitazone or tirzepatide for normal‑weight type 2 diabetes
Normal-weight Diabetes: Adipocyte-directed Therapy With Pioglitazone or Tirzepatide
This test will see if two fat‑targeting medicines, pioglitazone and tirzepatide, can improve insulin resistance and fat distribution in adults with normal‑weight type 2 diabetes compared with overweight people with diabetes and normal‑weight people without diabetes.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 104 (estimated) |
| Ages | 30 Years to 70 Years |
| Sex | All |
| Sponsor | Stanford University Academic / other |
| Locations | 2 sites (Palo Alto, California and 1 other locations) |
| Trial ID | NCT06657209 on ClinicalTrials.gov |
What this trial studies
The study compares three groups—normal‑weight people with type 2 diabetes, overweight people with type 2 diabetes, and normal‑weight people without diabetes—to define differences in fat cell function and fat distribution. Participants will undergo metabolic testing including OGTT and insulin resistance measures, body composition by DXA and MRI, and fat biopsies to analyze adipocyte biology. Individuals with normal‑weight diabetes will be treated with adipocyte‑directed therapies (pioglitazone or tirzepatide) and followed for changes in insulin sensitivity, fat distribution, and metabolic biomarkers. The goal is to link biological mechanisms in fat tissue to clinical metabolic outcomes and identify whether these therapies improve metabolic health in normal‑weight diabetes.
Who should consider this trial
Good fit: Ideal candidates are adults 30–70 years old with BMI 19–24.9 kg/m² and type 2 diabetes (A1c 5.7–8% or fasting glucose >100 mg/dL) who have had stable medications or lifestyle and stable weight for at least 3 months and are not using insulin or pioglitazone.
Not a fit: People who are overweight or obese, have type 1 diabetes, have uncontrolled diabetes (A1c >8%), are using insulin or pioglitazone, or are unwilling to undergo imaging and fat biopsy are unlikely to benefit from this specific study intervention.
Why it matters
Potential benefit: If successful, this could lead to treatments that specifically improve insulin sensitivity and healthy fat distribution for people with normal‑weight type 2 diabetes.
How similar studies have performed: Prior research shows pioglitazone can improve insulin sensitivity and tirzepatide has strong effects on glucose control and body composition, but using these drugs specifically to target adipocyte dysfunction in normal‑weight type 2 diabetes is relatively underexplored.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
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Where this trial is running
Palo Alto, California and 1 other locations
- Stanford University — Palo Alto, California, United States (Recruiting)
- Stanford University, Clinical and Translational Research Unit (CTRU) — Stanford, California, United States (Not_yet_recruiting)
Study contacts
- Study coordinator: Nina Shenoy, BS
- Email: nshenoy8@stanford.edu
- Phone: 408-896-0134
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.