Health TrialsbyHealthPanel

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

ConditionsDiabetes Mellitus, Type 2DiabetesType 2 DiabetesPre Diabetes
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age30-70
SponsorStanford University

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Crossover

Treatments tested in this trial

  • Insulin resistance testing

    Procedure/Surgery

    Steady state Plasma Glucose test

  • OGTT

    Procedure/Surgery

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

  • Fat biopsy

    Procedure/Surgery

    Needle biopsy to gather a sample of abdominal subcutaneous fat

  • DXA scan

    Radiation

    Whole body DXA scan

  • MRI

    Procedure/Surgery

    Abdominal MRI

  • 1H-MRS

    Procedure/Surgery

    Spectroscopy of the abdominal region

  • Tirzepatide

    Drug

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

  • Pioglitazone

    Drug

    16 weeks at a 45mg/day dose

Treatment groups

104 Participants
are divided into 3 treatment groups
Group A: Normal weight controlsOther 6 interventions
Group B: Normal weight with diabetes tirzepatide first pioglitazone secondExperimental treatment 8 interventions
Group C: Normal weight with diabetes pioglitazone first, tirzepatide secondExperimental treatment 8 interventions

Trial outcomes

Primary outcomes

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.

Time frame
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.

Time frame
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.

Time frame
Baseline comparisons between the groups

Secondary outcomes

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.

Time frame
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.

Time frame
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.

Time frame
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.

Time frame
Baseline comparisons

Other outcomes

1

Effect of adipose-directed therapy with tirzepatide on insulin resistance in men and women with normal weight diabetes (NWD).

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.

Time frame
16 weeks

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Stanford University

Lead sponsor

Source ClinicalTrials.gov
Apply now