Metformin and Molecular Aging in Prediabetes

NCT07302932 | Completed DMC

• 1 other identifier: 2.5/FCDOC/EC/HAO/2022-23
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

The incidence and prevalence of type 2 diabetes mellitus (T2DM) are increasing globally. The global prevalence of diabetes has nearly doubled since 1980, rising from 4.7% to 8.5% in the adult population. Asian Indians have one of the highest incidence rates of pre-diabetes (10.3%) and type 2 diabetes mellitus (T2DM) (8.8%) among all major ethnic groups, and the conversion from pre-diabetes to diabetes occurs more rapidly in this population. Metformin has been shown to effectively prevent the progression of prediabetes to overt diabetes. Furthermore, metformin improves lifespan in animal models through an anti-ageing pathway driven by mTOR. Metformin has also been shown to protect endothelial cells from hyperglycaemic damage by directly stimulating the expression of Sirtuin-1 (SIRT1), a deacetylase involved in metabolism and longevity by modulating SIRT1 downstream targets FoxO1 and p53/p21. It is important to note thatSIRT1, andmammalian target of rapamycin (mTOR) form a network that connects cellular metabolism and longevity programmes. Only one study is available which has explored the relationship of metformin with longevity. Previous study conducted a single-blind randomized placebo-controlled trial in prediabetic subjects in Italy (n, 38) who received metformin 1500mg/day (n, 19) or placebo (n, 19) for 2 months. They demonstrated that metformin use significantly increased insulin sensitivity and metabolic parameters, SIRT1 gene/protein expression, and SIRT1 promoter chromatin accessibility. They also demonstrated that metformin use increased mTOR gene expression with a concurrent decrease in p70S6K phosphorylation and altered the plasma N-glycan profile. These authors concluded that in individuals with prediabetes, metformin ameliorated effector pathways that have been shown to regulate longevity in animal models. The investigators recently did a study on 797 prediabetic women from north India (492 of whom were obese). In this study the investigators reported that age, obesity, and subcutaneous adiposity (predominantly truncal) are the main causes of leukocyte telomere shortening. It is yet unknown how metformin impacts aging-related genes and surrogate markers of ageing in the Asian Indian population. This clinical trial aims to evaluate the effects of metformin treatment on surrogate markers of ageing (leukocyte telomere length and telomerase activity), in the setting of pre-diabetes. We intend to compare treatment with metformin for six months, versus placebo in pre-diabetic subjects. We will assess the surrogate markers of ageing (leukocyte telomere length and telomerase activity) and the expression of longevity genes SIRT1, p66Shc, p53 and mTOR in peripheral blood mononuclear cells (PBMCs) before and after 6 months of metformin treatment.

Conditions

Metformin, Prediabetes

Outcome Measures

Primary Outcomes (2)

• Leukocyte telomerase length

  Leukocyte Telomere Length Measurement: LTL was analyzed using quantitative polymerase chain reaction (qPCR), comparing telomere repeat sequence copy number (T) to a reference single-copy gene (S). Relative fold changes in gene expression will be determined using the comparative threshold cycle method (ΔΔCq), comparing differences in threshold cycle values between groups.

  06 months

• Telomerase activity

  Telomerase activity was done by ELISA method

  06 months

Secondary Outcomes (1)

• Expression of longevity genes SIRT1, p66Shc, p53 and mTOR

  6 MONTHS

Other Outcomes (12)

• Weight

  06 month

• Height

  06 months

• Body Mass Index

  6 MONTHS

Study Arms (4)

placebo for six months

EXPERIMENTAL

Following a two-week diet and exercise run-in period, subjects will be randomized to receive either metformin (500mg twice daily after meals) or matching placebo for six months. All participants will monitor fasting and postprandial blood glucose (post-breakfast, post-lunch, post-dinner) monthly at home using a glucose meter. Both groups will maintain daily diaries recording tablet consumption and any missed doses. A three-month medication supply will be provided at each visit, with leftover tablets counted to assess compliance.

Drug: Metformin treatment

Effect of metformin treatment on Leukocyte telomere length

EXPERIMENTAL

Analyzed by qPCR for T/S ratio.

Drug: Metformin treatment; Drug: Analyzed by qPCR for T/S ratio.

To evaluate the effects of metformin treatment on telomerase activity

EXPERIMENTAL

Telomerase activity was done by ELISA Mathod

Drug: Metformin treatment

Expression of longevity genes SIRT1, p66Shc, p53 and mTOR

EXPERIMENTAL

Investigators were assessed the expression of longevity genes SIRT1, p66Shc, p53 and mTOR in peripheral blood mononuclear cells (PBMCs) before and after 6 months of metformin treatment.

Drug: Metformin treatment

Interventions

Metformin treatment DRUG

A computer-generated randomization sequence will be created by an independent statistician using an unrestricted scheme. Allocation will be concealed in serially numbered, sealed, opaque envelopes held by non-study office staff. After a two-week diet and exercise run-in period, subjects will be randomized to receive either metformin (500mg twice daily) or placebo for six months. Participants will monitor fasting and postprandial blood glucose monthly at home. Medication adherence will be tracked through daily diaries and pill counts at three-month visits. Compliance (target ≥85%) will be maintained through biweekly phone calls (urban areas), bi-monthly home visits by health workers (rural areas), and three-monthly motivational sessions.

Also known as: Placebo

Effect of metformin treatment on Leukocyte telomere length; Expression of longevity genes SIRT1, p66Shc, p53 and mTOR; To evaluate the effects of metformin treatment on telomerase activity; placebo for six months

Analyzed by qPCR for T/S ratio. DRUG

Analyzed by qPCR for T/S ratio.

Effect of metformin treatment on Leukocyte telomere length

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 30-60 years Both genders (male and female)
• Diagnosis of pre-diabetes, defined as:
• Impaired Fasting Glucose (IFG): Fasting plasma glucose 100-125 mg/dL AND/OR Impaired Glucose Tolerance (IGT): 2-hour plasma glucose 140-199 mg/dL after 75 g oral glucose tolerance test (OGTT)
• IGT is mandatory (i.e., every participant must have IGT, even if IFG is also present)

You may not qualify if:

• Type 1 diabetes mellitus Type 2 diabetes mellitus Pregnancy or lactation Hypoglycemia (blood glucose \<70 mg/dL) after medication Acute or chronic inflammatory diseases Immunological diseases (e.g., autoimmune diseases) History of organ transplantation Current or recent steroid therapy Uncontrolled arterial hypertension Known allergy or intolerance to metformin Major surgery or cardiovascular events (e.g., myocardial infarction, stroke) within the last 3 months

Sponsors & Collaborators

• Diabetes Foundation, India: lead

Study Sites (1)

Anoop misra

New Delhi, National Capital Territory of Delhi, 110048, India

Location

MeSH Terms

Conditions

Prediabetic State

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Patients were recruited from Fortis C-DOC OPD.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This clinical trial aims to evaluate the effects of metformin treatment on surrogate markers of ageing (leukocyte telomere length and telomerase activity), in the setting of pre-diabetes. We intend to compare treatment with metformin for six months, versus placebo in pre-diabetic subjects. We will assess the surrogate markers of ageing (leukocyte telomere length and telomerase activity) and the expression of longevity genes SIRT1, p66Shc, p53 and mTOR in peripheral blood mononuclear cells (PBMCs) before and after 6 months of metformin treatment.

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: December 24, 2025
• Study Start: February 1, 2023
• Primary Completion: January 30, 2025
• Study Completion: January 30, 2025
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)