This week, after our publisher Steve Freed was able to connect up with Dr. Vinik again, we bring you more insight on the latest in GLP-1 therapy.
I asked Dr. Vinik , “Who is the ideal type 2 patient for GLP-1 treatment?” and “Can GLP-1 drugs prevent apoptosis and regenerate betacells?” and here is what he had to say….
What is the profile for the ideal candidate for GLP-1 therapy?
Dr. Vinik: The ideal candidate for monotherapy with a GLP-1 analog is a person with type 2 diabetes and overweight with an A1c no more than 1.5% above goal and there are many factors determining how aggressive one should be but let’s just say 6.5% if diabetes is <12-15years duration, there is no history of CVD, no coronary calcification, normal renal function, a male and Caucasian, and absence of autonomic dysfunction and no history of neuropathy. If all these criteria are not met ease off on the A1c target to maybe 7.5%.
Dr. Vinik: Type 1 diabetes until there is more evidence of activity. There should be no history or objective evidence of gastroparesis since this places the person at risk of a bezoar (a mass found trapped in the gastrointestinal system usually in the stomach). The side effects of nausea, vomiting and loss of hedonism would no doubt speak for themselves, hence the high risk of failure in the early trials. Until all the evidence is in we should avoid patients with a history of pancreatitis and medullary carcinoma of the thyroid, C cell hyperplasia and multiple endocrine neoplasia type 2.
Dr. Vinik: Certainly when first line therapy with metformin has failed and in patients not at goal on two or more agents. The decision on whether or not to use insulin or a GLP-1 analog remains in dispute but if the A1C is > 9% the choice should be insulin.
What is GLP-1’s effect on homeostasis, decreasing beta-cell workload, and improving beta-cell response?
Dr. Vinik: Improving beta cell function, delay in gastric emptying and a central effect on appetite and satiety. The data on islet regeneration and or prevention of apoptosis in the human have not been established.
What is GLP-1’s effect on beta cells in reducing apoptosis and stimulating regeneration?
Dr. Vinik: Depending on the animal model you use, one can find both evidence for stimulation of neogenesis and an apoptotic effect. However this is open to question since many of the animal models used have a proclivity to spontaneous regeneration while others are resistant and age and other factors are determinants of response accounting for discrepancies in the literature. What is clear in the human situation is that GLP-1 enhances beta cell function with an increase in the ability to secrete insulin and restore first phase insulin release, a critical determinant of normal glucose tolerance. There is however, no data that irrefutably supports an action on neogenesis or anti-apoptosis in humans.
One of the leading diabetes researchers in the world, Dr. Aaron I. Vinik leads the EVMS Strelitz Diabetes Center’s quest to cure diabetes. Internationally renowned for his research in the areas of hormone secreting tumors and the chronic complications of diabetes, Dr. Vinik has presented his work all over the world. Dr. Aaron I. Vinik has written five books, published more than 250 papers in medical journals, and is recognized as a pioneer and scholar. Dr. Vinik has received research funding for his studies from the National Institutes of Health, the National Cancer Institute, the Kroc Foundation and the American Diabetes Association. He is a leader in research on the diagnosis and treatment of diabetic neuropathy with a particular expertise in the area of autonomic diabetic neuropathy, a complex and challenging condition. Dr. Vinik has also been a leader in research on new approaches to generate islet cell tissue from pancreatic duct tissue which may one day lead to a true cure for diabetes.