Information source: Mayo Clinic
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Insulin Resistance; Prediabetic State
Intervention: Metformin (Drug); Placebo (Drug)
Phase: N/A
Status: Active, not recruiting
Sponsored by: Mayo Clinic
Official(s) and/or principal investigator(s):
K Nair, MD, PhD, Principal Investigator, Affiliation: Mayo Clinic
Summary
This study is being done to understand metformin's mechanisms of action regarding glucose
production, protein metabolism, and mitochondrial function.
Clinical Details
Official title: Metformin's Effect on Glucagon-induced Endogenous Glucose Production, Protein Metabolism and Resting Energy Expenditure in Insulin Resistant Individuals.
Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
Primary outcome: Change in Glucagon-induced endogenous glucose production.
Secondary outcome: Change in glucagon-induced alterations in whole body protein metabolism and resting energy expenditure.
Detailed description:
It is believed that Metformin antagonizes the action of glucagon through different pathways.
In mice, Metformin leads to inhibition of adenylate cyclase, reduction of levels of cyclic
AMP and protein kinase A (PKA) activity, therefore blocking glucagon-dependent glucose
output form hepatocytes. Glucagon plays an important role in the increased catabolic state
seen in insulin deficiency. Hyperglucagonaemia states have been shown to accelerate
proteolysis and leucine oxidation in insulin-deficient humans. Patients with insulin
resistance and increased levels of glucagon have an increased in energy expenditure which
may contribute to the catabolic state associated with this condition. We hypothesized that
treatment with Metformin for 2 weeks will significantly inhibit glucagon-induced endogenous
glucose production in insulin resistant individuals. We also hypothesized that
glucagon-induced alterations in whole body protein metabolism and the increases in O2
consumption associated with hyperglucagonaemia states will be significantly inhibited by
Metformin in these individuals. This would open the door for the development of other
antidiabetic drugs with antagonism of glucagon as their principal mechanism of action.
Eligibility
Minimum age: 35 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 35-65 years of age
- Fasting blood glucose >100 mg/dl
- BMI 27-36 kg/m2
- Waist Circumference: Men ≥ 104 cm; women ≥ 88 cm
- If previously on anti-diabetic medication, should be off for at least 1 month
Exclusion Criteria:
- Active use of hypoglycemic agents (< 1 month)
- Renal failure, creatinine ≥ 1. 5 mg/dL in men or ≥ 1. 4 mg/dL in women
- Alanine aminotransferase levels exceed 135 IU/L or aspartate aminotransferase levels
exceed 129 IU/L (3 x the upper limit of normal)
- Congestive Heart Failure (EF < 40 %)
- Active coronary artery disease
- Recent (less than 6 weeks) or planned imaging study requiring IV contrast
- Participation in structured exercise (> 2 hr per week)
- Recent change in dietary habits or weight
- Tobacco use
- Use of systemic glucocorticoids
- Anti-coagulant therapy (warfarin/heparin)
- Pregnancy or breastfeeding
- Alcohol consumption greater than 2 drinks/day
- Uncontrolled Hypothyroidism, abnormal thyroid stimulating hormone levels
- Metformin Allergy
Locations and Contacts
Mayo Clinic in Rochester, Rochester, Minnesota 55905, United States
Additional Information
Starting date: October 2013
Last updated: May 13, 2015