Metformin Pharmacogenomics: Current Status and Future Directions

The incidence of type 2 diabetes (T2D) and its costs to the health care system continue to rise. Despite the availability of at least 10 drug classes for the treatment of T2D, metformin remains the most widely used first-line pharmacotherapy for its treatment; however, marked interindividual variability in response and few clinical or biomarker predictors of response reduce its optimal use. As clinical care moves toward precision medicine, a variety of broad discovery-based “omics” approaches will be required. Technical innovation, decreasing sequencing cost, and routine sample storage and processing has made pharmacogenomics the most widely applied discovery-based approach to date. This opens up the opportunity to understand the genetics underlying the interindividual variation in metformin responses in order for clinicians to prescribe specific treatments to given individuals for better efficacy and safety: metformin for those predicted to respond and alternative therapies for those predicted to be nonresponders or who are at increased risk for adverse side effects. Furthermore, understanding of the genetic determinants of metformin response may lead to the identification of novel targets and development of more effective agents for diabetes treatment. The goals of this workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases were to review the state of research on metformin pharmacogenomics, discuss the scientific and clinical hurdles to furthering our knowledge of the variability in patient responses to metformin, and consider how to effectively use this increased understanding to improve patient outcomes

Diabetes and Cardiovascular Disease in Older Adults: Current Status and Future Directions

The prevalence of diabetes increases with age, driven in part by an absolute increase in incidence among adults aged 65 years and older. Individuals with diabetes are at higher risk for cardiovascular disease, and age strongly predicts cardiovascular complications. Inflammation and oxidative stress appear to play some role in the mechanisms underlying aging, diabetes, cardiovascular disease, and other complications of diabetes. However, the mechanisms underlying the age-associated increase in risk for diabetes and diabetes-related cardiovascular disease remain poorly understood. Moreover, because of the heterogeneity of the older population, a lack of understanding of the biology of aging, and inadequate study of the effects of treatments on traditional complications and geriatric conditions associated with diabetes, no consensus exists on the optimal interventions for older diabetic adults. The Association of Specialty Professors, along with the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and the American Diabetes Association, held a workshop, summarized in this Perspective, to discuss current knowledge regarding diabetes and cardiovascular disease in older adults, identify gaps, and propose questions to guide future research

Diabetes in Older Adults

More than 25 % of the U.S. popula-tion aged $65 years has diabetes(1), and the aging of the overall population is a significant driver of the diabetes epidemic. Although the burden of diabetes is often described in terms of its impact on working-age adults, diabetes in older adults is linked to highermortality, reduced functional status, and increased risk of institutionalization (2). Older adults with diabetes are at substantial risk for both acute and chronic microvascular and car-diovascular complications of the disease. Despite having thehighest prevalence of diabetes of any age-group, older persons and/or those with multiple comorbidities have often been excluded from randomize