Improve PAD PERformance with METformin. The PERMET Trial.

As a co-investigator in the PERMET TRIAL (Northwestern University, PI: Mary McGrae McDermott, MD), I will measure changes in calf skeletal muscle capillary density, mitochondrial content and activity and autophagy in response to metformin in frozen human muscle biopsies shipped to the University of Kentucky from Northwestern University. We have budgeted for immunohistochemical analyses of muscle cross-sections from 30-40 subjects per year for 5 years. Digital microscopic images, as well as quantification of the images, will be provided to investigators at Northwestern quarterly. We will communicate regularly by phone, email and video conferencing, and I will attend at least one meeting annually at Northwestern University. This component of the PERMET TRIAL enables us to delineate biologic pathways underlying the beneficial effects of metformin in patients with PAD. Identifying biologic mechanisms will help identify new therapies, with similar biologic actions, that improve walking performance in people with PAD.