Antecedent Metabolic Health and Metformin Aging Study

Summary

Aging is the number one risk factor for the majority of chronic diseases. There are no pharmaceutical treatments to slow aging and prolong healthspan. The anti-diabetic drug metformin is considered a likely pharmaceutical candidate to slow aging. In this study, the investigators hypothesize that metformin treatment in subjects free of type 2 diabetes will improve insulin sensitivity and glucoregulation in insulin resistant individuals, but will decrease insulin sensitivity and glucoregulation in insulin sensitive subjects. Further, the investigators hypothesize that long-term metformin treatment will remodel mitochondria in a way that decreases mitochondrial function in subjects that are insulin sensitive, but improves mitochondrial function in subjects that are insulin resistant. The investigators will use a dual-site, 12- week drug intervention trial performed in a double-blind, placebo-controlled manner on 148 subjects recruited from two separate sites (Oklahoma Medical Research Foundation (OMRF) and University of Wisconsin-Madison (UWM)). After consent and initial subject screening for chronic disease, subjects will be stratified to insulin sensitive (IS) or insulin resistant (IR) groups. Over a 12- week intervention, half of each group will take metformin and half will take a placebo. Pre- and post--intervention, subjects will complete a series of procedures to assess insulin sensitivity, glucose regulation, and biomarkers of aging. The same subjects will provide a skeletal muscle biopsy pre-- and post-intervention to assess the change in mitochondrial function and mitochondrial remodeling with and without metformin treatment. By completion of this project, the investigators expect to provide evidence that helps further delineate who may benefit from metformin treatment to slow aging.

Conditions

• Aging
• Insulin Sensitivity
• Chronic Disease
• Mitochondria
• Insulin Resistance

Interventions

DRUG

Metformin

Metformin (Hunter Pharmacy) following a "ramp up" dosing protocol with a targeted dose of 1500 mg/day for 12 weeks.

DRUG

Placebo oral tablet

Silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate

Sponsors & Collaborators

• National Institute on Aging (NIA)

  collaborator NIH

• University of Oklahoma

  collaborator OTHER

• University of Wisconsin, Madison

  collaborator OTHER

• Oklahoma Medical Research Foundation

  lead OTHER

Principal Investigators

• Benjamin F Miller, PhD · Oklahoma Medical Research Foundation

• Adam Konopka, PhD · University of Wisconsin, Madison

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

40 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-07-29

Primary Completion

2025-03-12

Completion

2025-03-12

FDA Drug

Yes

Countries

• United States

Study Locations