Metformin to Augment Strength Training Effective Response in Seniors (MASTERS): Study protocol for a randomized controlled trial

Doug E. Long, Bailey D. Peck, Jenny L. Martz, S. Craig Tuggle, Heather M. Bush, Gerald McGwin, Philip A. Kern, Marcas M. Bamman, Charlotte A. Peterson

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Background: Muscle mass and strength are strong determinants of a person's quality of life and functional independence with advancing age. While resistance training is the most effective intervention to combat age-associated muscle atrophy (sarcopenia), the ability of older adults to increase muscle mass and strength in response to training is blunted and highly variable. Thus, finding novel ways to complement resistance training to improve muscle response and ultimately quality of life among older individuals is critical. The purpose of this study is to determine whether a commonly prescribed medication called metformin can be repurposed to improve the response to resistance exercise training by altering the muscle tissue inflammatory environment. Methods/design: Individuals aged 65 and older are participating in a two-site, randomized, double-blind, placebo-controlled trial testing the effects of metformin or placebo on muscle size, strength, and physical function when combined with a progressive resistance training program. Participants consume 1700mg of metformin per day or placebo for 2weeks before engaging in a 14-week progressive resistance training regimen, with continued metformin or placebo. Participants are then monitored post-training to determine if the group taking metformin derived greater overall benefit from training in terms of muscle mass and strength gains than those on placebo. Muscle biopsies are taken from the vastus lateralis at three time points to assess individual cellular and molecular adaptations to resistance training and also changes in response to metformin. Discussion: The response of aged muscles to a resistance training program does not always result in a positive outcome; some individuals even experience a loss in muscle mass following resistance training. Thus, adjuvant therapies, including pharmacological ones, are required to optimize response to training in those who do not respond and may be at increased risk of frailty. This is the first known metformin repurposing trial in non-diseased individuals, aimed specifically at the resistance exercise "non-responder" phenotype present in the aging population. The overall goal of this trial is to determine if combined exercise-metformin intervention therapy will benefit older individuals by promoting muscle hypertrophy and strength gains, thereby maintaining functional independence. Trial registration:, NCT02308228. Registered on 25 November 2014.

Original languageEnglish
Article number192
Issue number1
StatePublished - Apr 26 2017

Bibliographical note

Funding Information:
The study was funded by the National Institutes of Health - National Institute on Aging grant AG046920 and supported by the NIH Clinical and Translational Science Awards (CTSA) (UL1TR001998) at the University of Kentucky and the NIH CTSA (UL1TR000165) at the University of Alabama at Birmingham. The NIH had no role in the design of the study, collection, analysis, or interpretation of data, or in writing the manuscript.

Publisher Copyright:
© 2017 The Author(s).


  • Aging
  • Inflammation
  • Medication
  • Metformin
  • Placebo
  • Resistance exercise
  • Sarcopenia
  • Skeletal muscle

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)


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