Perspectives on the Late Breaking Abstracts at the ADA Scientific Sessions
June 29, 2010
Harold Lebovitz, MD
The ADA Scientific Sessions are a high point for diabetes research each year, with an enormous amount of clinical and basic research showcased during the meeting and myriad opportunities to discuss these data with assembled peers. Of all the presentations at the meeting, the late-breaking abstracts typically represent the latest, hot-off-the-press research, submitted and accepted for presentation just weeks prior to the live meeting in June. This year was no exception, and a number of interesting clinical studies were reported in the late-breaking abstract sessions.
As in the main ADA program, the GLP-1 receptor agonist/incretin therapeutic class was well-represented in the late-breaking sessions. Importantly, the GLP-1 class presentations reported reductions in A1C without an increased risk for hypoglycemia. Head-to-head studies showed exenatide once weekly to have greater A1C reduction compared to exenatide twice-daily, and liraglutide to have greater A1c reduction compared to sitagliptin. Data from these clinical trials made direct head-to-head comparisons of these therapeutic options in the incretin class, including efficacy comparisons of A1C, fasting plasma glucose and reductions in body weight. These head-to-head studies also assessed the safety and tolerability, including rates of nausea and hypoglycemia, of incretin therapy. In addition, three studies presented data on decreases in A1C with the combined use of exenatide twice daily (targeting mealtime glucose) with titrated basal insulin targeting fasting glucose. Several presentations examined safety concerns of the incretin class, including pancreatitis in a preclinical model and renal function in humans through epidemiological databases. Finally, several studies presented new technologies for the administration of exenatide, including continuous subcutaneous infusion and oral delivery that previewed potential therapeutic options of the future.
Sodium glucose transporter (SGLT) inhibition is another interesting experimental approach to treating diabetes. Sodium-dependent glucose transporters are specifically expressed in the intestines (SGLT-1) and kidneys (SGLT-2), suppressing glucose absorption from the gut and blocking glucose reabsorption from renal filtrate. Thus, SGLT inhibitors represent a novel approach to affecting glucose metabolism. This novel approach was represented in the sessions with new data on dapaglaflozin, a late-stage molecule in development. Dapaglaflozin is a selective inhibitor of the SGLT2 transporter and is being evaluated for potential use in patients failing insulin treatment. Early phase data was also presented on a novel dual SGLT inhibitor (LX4211) that targets both SGLT2 and SGLT1 receptor subtypes. Importantly, this is another class that has reported reductions in A1C without an increased risk for hypoglycemia.
The overarching aspirational goal for diabetes treatment is the preservation of beta-cell function and beta-cell mass. An early-stage study of valsartan studied the effects of the compound on beta-cell function and insulin sensitivity in normotensive patients with IFG or IGT as possible mechanisms for the recently published clinical trial that showed valsartin to decrease, or delay by 14%, the conversion of prediabetes to diabetes. Valsartan is currently approved for use as an anti-hypertensive. Studying beta-cell function is relatively straightforward; however it is inherently difficult to directly assess beta-cell mass, preservation and/or regeneration in humans. To help address these issues, a novel in-vivo PET-based method for examining beta cell mass in humans with type 1 diabetes by evaluating molecules co-expressed with insulin was presented. If this technique proves to be sensitive enough, one could imagine its use in combination with well-characterized clamp techniques in patients with type 1 and type 2 diabetes to correlate beta cell function with changes in beta-cell mass.
Several studies describing therapies in early development were also featured, including a dual PPAR (alpha/delta) agonist. Much like the specific PPAR agonists, dual PPAR agonists work on pathways affecting both lipid and glucose homeostasis. Also, data on an A1 adenosine receptor agonist was presented, focusing on intracellular free fatty acid concentrations that may impact insulin sensitivity and glucose homeostasis.
Finally, a large number of presentations were focused on technological advances in diabetes treatment and prevention. A number of studies examined the effects that glucose monitoring systems and technology-based support systems have on patients’ understanding of their day-to-day glycemic status and diabetes management. In addition, the session highlighted several platforms in development to identify genetic markers that are predictive of the risk of developing disease, and the characterization of biochemical markers that may serve as useful surrogates for clinical endpoints in patients with diabetes and cardiovascular disease.
Overall, the late-breaking session provided a packed agenda. It was exciting as it gave us insight and hope that we are making progress in bringing new therapies to patients, and reminds us of the challenges and work that lie ahead in order to help patients manage their diabetes and live a healthier life.
Harold Lebovitz is a professor of Medicine at the Division of Endocrinology and Metabolism/Diabetes at the State University of New York, Health Sciences Center at Brooklyn.
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