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Metformin and Longevity Genes in Prediabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01765946
Recruitment Status : Completed
First Posted : January 11, 2013
Last Update Posted : March 13, 2013
Information provided by (Responsible Party):
Angelo Avogaro, University of Padova

Brief Summary:
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 or disease Intervention/treatment Phase
Insulin Resistance Prediabetes Aging Inflammation Drug: Metformin Drug: placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Effects of Metformin on Longevity Gene Expression and Inflammation and Prediabetic Individuals. A Placebo-controlled Trial
Study Start Date : June 2010
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 :
  1. Insulin sensitivity [ Time Frame: 2 months after treatment ]
    A dynamic measure of insulin sensitivity (Si) from the frequently sampled OGTT

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

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01765946

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University Hospital Diabetes Outpatient Clinic
Padova, Italy, 35128
Sponsors and Collaborators
University of Padova
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Principal Investigator: Angelo Avogaro, M.D. Ph.D. University of Padova
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Angelo Avogaro, Full professor of Endocrinology and Metabolism, University of Padova Identifier: NCT01765946    
Other Study ID Numbers: MetAge
First Posted: January 11, 2013    Key Record Dates
Last Update Posted: March 13, 2013
Last Verified: March 2013
Keywords provided by Angelo Avogaro, University of Padova:
Insulin resistance
Longevity genes
Additional relevant MeSH terms:
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Insulin Resistance
Prediabetic State
Glucose Intolerance
Pathologic Processes
Glucose Metabolism Disorders
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs