Tuesday, April 5, 2016

Patient-centered diabetes research needs primary care perspectives

- Kenny Lin, MD, MPH

A Letter to the Editor in AFP's March 15th issue pointed out that a simplified management algorithm in a previous article on noninsulin therapies for type 2 diabetes could have been misinterpreted to suggest the non-recommended combination of a dipeptidyl-peptidase-4 (DPP-4) inhibitor and a glucagon-like-peptide-1 (GLP-1) receptor agonist. According to the American Diabetes Association's 2016 Standards of Medical Care in Diabetes, however, there is little comparative data to guide second-line drug choice after metformin. Few other medications have been shown to lower mortality in patients with type 2 diabetes, and even then only in specific populations, as Dr. Middleton discussed in a recent AFP Community Blog post.

The National Institutes of Health is currently recruiting patients for a multicenter randomized trial, the Glycemia Reduction Approaches to Diabetes: A Comparative Effectiveness (GRADE) study, that will compare the benefits and harms of four medications commonly combined with metformin: 1) glimepride (a sulfonylurea); 2) sitagliptin (a DPP-4 inhibitor); 3) liraglutide (a GLP-1 receptor agonist); and 4) glargine insulin. Since the GRADE study was planned, the sodium glucose cotransporter 2 (SGLT-2) inhibitor class has come on the market, and a randomized trial found that empagliflozin reduces cardiovascular and all-cause mortality in patients with established cardiovascular disease and type 2 diabetes. This surprising result led some experts to suggest that SGLT-2 inhibitors be added to the GRADE trial or incorporated into some other comparative research study.

This kind of pragmatic diabetes research would seem to be a perfect fit for the Patient-Centered Outcomes Research Institute (PCORI). Created by the Affordable Care Act, PCORI's mission is to "improve the quality and relevance of evidence available to help patients, caregivers, clinicians, employers, insurers, and policy makers make informed health decisions" by funding comparative clinical effectiveness research and research methods. However, PCORI received criticism recently after an independent analysis of its first 6 funding cycles by the American Academy of Family Physicians' Robert Graham Center concluded that "less than one-third of PCORI studies involve or are relevant to primary care."

Last month, I represented the AAFP in the PCORI stakeholder workshop "Prioritizing Comparative Effectiveness Research for Second-Line Type 2 Diabetes Treatment." Other workshop participants included fellow primary care clinicians and representatives from relevant subspecialty societies, patient groups, benefits managers, clinical investigators, and the pharmaceutical industry. After listening to presentations on recent trials and the GRADE study, we were asked to formulate a research question in the PICO (Population, Intervention, Comparator, Outcome) format, keeping in mind the following criteria: patient-centeredness, health impact of the condition, assessment of current options, likelihood of implementation in practice, and durability of information.

I was impressed by the high quality of the discussion and the group's determination to come up with practical research questions that would provide meaningful answers to better inform family physicians and other clinicians who care for patients with type 2 diabetes. PCORI Executive Director Joe Selby, MD, MPH, who is also a family physician, told me how important it was to him that Family Medicine be actively engaged in shaping the organization's research agenda and priorities. For interested readers, PCORI offers many opportunities to get involved that range from suggesting new research questions, to providing input on current questions and methods, to serving on standing advisory panels on various cross-cutting topics.