Antihyperglycemic Treatment Intensification and Clinical Outcomes: A Pilot Study

Grant Winners

Dean

Abstract

Type 2 diabetes poses a societal burden within the United States (U.S.), despite the health care system spending millions of dollars on complexantihyperglycemic regimens that have a high pill burden. In addition, glucose control among patients with this condition have remained poor. Scientific evidence from randomized clinical trials have demonstrated that consistently low glycemic levels reduce the incidence of long-term complications and that single-drug anti-hyperglycemic regimens intensified to dual- (two drug classes) and triple- (three drug classes) anti- hyperglycemic regimens can reduce blood glucose levels to achieve glycemic goals. However, direct scientific evidence showing benefits of antihyperglycemic regimen intensification to dual- and triple-regimens in slowing cardiovascular disease and decline of renal function is unclear and of low or insufficient quality. Comparative effectiveness research aims to inform decision makers about "what works best" by comparing currently available medical interventions. Due to the growing use of electronic health records in health systems, this clinical data can be combined with insurance claims data to make high quality observational studies that provide "real-world" evidence to decision makers. This pilot study will provide the foundation for further research supported by extramural funding to address the mentioned research gap by analyzing data from up to 10 years of follow-up in one large healthcare system. We hypothesize that dual-therapy regimen is the most effective approach for the treatment of diabetes and that addition of a third antihyperglycemic medication will not reduce the incidence of long-term cardiovascular or renal outcomes. To evaluate this hypothesis and estimate the treatment effect of intensifying antihyperglycemic therapy from dual to triple therapy on cardiovascular and renal outcomes, this study will use a longitudinal observational design from existing clinical and claims data from the University of Pittsburgh health system via their R3 Program. This Program and its data are specifically designed to answer comparative effectiveness research questions. This overall hypothesis will be evaluated using the following specific aims: to evaluate the treatment effect of intensifying anti- hyperglycemic therapy from dual to triple therapy on: 1) time to any cardiovascular event, and 2) the rate of estimated glomerular filtration rate (eGFR) decline. Expected outcomes of this study will provide important preliminary data for a larger and more diverse study using a greater number of health systems and possibly inform future clinical trials of antihyperglycemic agents on cardiovascular and renal outcomes.