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

NCT01956929 | Completed Phase 1

• 1 other identifier: 13-004966
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Insulin Resistance; Prediabetic State

Keywords

Insulin Resistance; Prediabetic State; Metformin

Outcome Measures

Primary Outcomes (1)

• Change in Glucagon-induced endogenous glucose production.

  To assess the effect of Metformin on glucose metabolism, at baseline and during a period of hyperglucagonemia, endogenous glucose production will be measured using a stable isotope tracer during the application of a somatostatin-based pancreatic clamp. Participants will be assessed before and following two weeks of consuming either metformin or placebo.

  Measured at week 0, 2, 4, 6 and 8

Secondary Outcomes (1)

• Change in glucagon-induced alterations in whole body protein metabolism and resting energy expenditure.

  Measured at week 0, 2, 4, 6 and 8

Study Arms (2)

Metformin

EXPERIMENTAL

2 weeks of Metformin use. First week 1000mg/day, Second week Max dose of 2000 mg/day.

Drug: Metformin

Placebo

PLACEBO COMPARATOR

2 weeks of Placebo (lactulose pills)

Drug: Placebo

Interventions

Metformin DRUG

Metformin 1000mg daily for one week, then 2000 mg daily for the second week. 4 week washout period, then crossover to placebo.

Also known as: Glucophage

Metformin

Placebo DRUG

Placebo tablets for 2 weeks, then 4 weeks of washout period, then crossover to metformin.

Also known as: Lactulose

Placebo

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Insulin Resistance; Prediabetic State

Interventions

Metformin; Lactulose

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Officials

• K Nair, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 23, 2013
• First Posted: October 8, 2013
• Study Start: October 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: September 1, 2017

Record last verified: 2017-08

Locations

US (1)