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Metformin and Longevity Genes in Prediabetes

This study has been completed.
Information provided by (Responsible Party):
Angelo Avogaro, University of Padova Identifier:
First received: January 8, 2013
Last updated: March 12, 2013
Last verified: March 2013
Pre-diabetes, a condition characterized by hyperglycaemia, is associated with increased cardiovascular risk and reduced life expectancy, as compared to the general population. AMP-activated protein kinase (AMPK) is an enzyme that plays a key role in cellular energy homeostasis and metabolism, and recently it has been demonstrated that AMPK regulates aging pathways, as well. AMPK is susceptible to modulation through pharmacologic (e.g. metformin) and non-pharmacologic (e.g. physical exercise) interventions. This clinical trial aims to describe the effects of the AMPK pathway on longevity genes and inflammation in the setting of pre-diabetes in vivo and in vitro. To this end, the investigators will compare treatment with metformin (500 mg t.i.d) for 2 months, versus placebo in pre-diabetic subjects. The investigators will assess expression of longevity genes SIRT1, p66Shc, p53 and mTOR in peripheral blood mononuclear cells (PBMCs) ex vivo. The investigators will evaluate monocyte polarization by flow cytometry, according to the expression of surface antigens (CD68, CCR2, CD163, CD206, CX3CR1) to determine the prevalence of pro- or anti-inflammatory cells. Inflammatory cytokines (TNF-alpha, MCP-1, IL-1, IL-6, IL-10, CCL12) will also be determined. In the in vitro study the investigators will evaluate the effects of AMPK activation or inhibition on longevity gene and protein expression.

Condition Intervention Phase
Insulin Resistance
Drug: Metformin
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Participant)
Primary Purpose: Treatment
Official Title: Effects of Metformin on Longevity Gene Expression and Inflammation and Prediabetic Individuals. A Placebo-controlled Trial

Resource links provided by NLM:

Further study details as provided by University of Padova:

Primary Outcome Measures:
  • Longevity gene expression [ Time Frame: 2 month after treatment ]
    Change in the expression of longevity genes Sirtuin-1, p66Shc, mTor, p53 in peripheral blood mononuclear cells (PBMC)

Secondary Outcome Measures:
  • Insulin sensitivity [ Time Frame: 2 months after treatment ]
    A dynamic measure of insulin sensitivity (Si) from the frequently sampled OGTT

  • Monocyte polarization status [ Time Frame: 2 months after treatment ]
    Polarization of circulating monocytes in M1 (CD68+CCR2+) and M2 (CX3CR1+CD163+/CD206+)

Enrollment: 38
Study Start Date: June 2010
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Metformin tablets 500 mg tid for 2 months
Drug: Metformin
Metformin tablets 500 mg tris in die (tid)
Other Name: Glucophage
Placebo Comparator: Placebo
Placebo tables tid for 2 months
Drug: placebo


Ages Eligible for Study:   40 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Pre-diabetes, defined as IFG (fasting glucose between 100 and 125 mg/dl) or IGT (2h post-oral glucose load (75g) between 140 and 199 mg/dl);
  • Age 40-75 years;
  • Both genders.

Exclusion Criteria:

  • Type 1 or 2 diabetes mellitus;
  • Pregnancy, lactation;
  • Acute, chronic or inflammatory diseases;
  • Neoplasms;
  • Immunological diseases, organ transplantation, steroid therapy;
  • Uncontrolled arterial hypertension (systolic pressure > 180 mmHg or diastolic > 120 mmHg);
  • Recent(within 3 months) surgical intervention or cardiovascular accidents;
  • Known allergy to metformin.
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Please refer to this study by its identifier: NCT01765946

University Hospital Diabetes Outpatient Clinic
Padova, Italy, 35128
Sponsors and Collaborators
University of Padova
Principal Investigator: Angelo Avogaro, M.D. Ph.D. University of Padova
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Angelo Avogaro, Full professor of Endocrinology and Metabolism, University of Padova Identifier: NCT01765946     History of Changes
Other Study ID Numbers: MetAge
Study First Received: January 8, 2013
Last Updated: March 12, 2013

Keywords provided by University of Padova:
Insulin resistance
Longevity genes

Additional relevant MeSH terms:
Prediabetic State
Glucose Intolerance
Insulin Resistance
Pathologic Processes
Glucose Metabolism Disorders
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs processed this record on April 21, 2017