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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


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.


Minimum age: 35 Years. Maximum age: 65 Years. Gender(s): Both.


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

Page last updated: August 23, 2015

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