NCT01956929

Metformin's Effect on Glucagon-induced Glucose Production and Protein Metabolism.

Metformin's Effect on Glucagon-induced Endogenous Glucose Production, Protein Metabolism and Resting Energy Expenditure in Insulin Resistant Individuals.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 35 Years – 65 Years
• Healthy volunteers: Accepted

Summary

This study is being done to understand metformin's mechanisms of action regarding glucose production, protein metabolism, and mitochondrial function.

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.

Conditions

• Insulin Resistance
• Prediabetic State

Interventions

Type	Name	Description
DRUG	Metformin	Metformin 1000mg daily for one week, then 2000 mg daily for the second week. 4 week washout period, then crossover to placebo.
DRUG	Placebo	Placebo tablets for 2 weeks, then 4 weeks of washout period, then crossover to metformin.

Timeline

• Start date: 2013-10-01
• Primary completion: 2016-03-01
• Completion: 2016-03-01
• First posted: 2013-10-08
• Last updated: 2017-09-01

Locations

1 site across 1 country: United States