MD Conference Express - (Page 33)

S E L E C T E D U P D A T E S I N N E W E R I N S U L I N S n Are New Insulins Just a Breath Away? Written by Neil Canavan and Heather Q. Sinclair A great deal of progress is being made in the area of insulin therapy. The goal of these new therapeutic approaches is to address three distinct needs: 1) the need for so-called “warpspeed insulins” as an improvement over rapid-acting formulations, 2) the need for a more efficient, long-acting basal insulin, and 3) the need to reduce or eliminate the use of needles. Michael Weiss, MD, PhD, Case Western Reserve University, Cleveland, OH, explained the medical need of “warp-speed” (ultrarapid absorption) insulin. “Warp-speed insulins” may mimic first-phase insulin secretion more efficiently to prevent immediate postprandial hyperglycemia. Additionally, they may reduce late postprandial hypoglycemia and the pharmacokinetic (PK) variability that is currently observed within and between patients. The technical hurdle to achieving these goals is to stabilize the aggregate form of insulin prior to administration while at the same time ensuring rapid dissociation of injected hexameric complex to the therapeutically active insulin monomer. Methods to achieve rapid absorption have included delivery systems (microneedle patch), chemical accelerants (EDTA/citrate; VIAject), the use of an enzymatic environment (hyaluronidase co-injection), and protein engineering [Forst T et al. Diabetes Care 2010; Muchmore DB et al. J Diabetes Sci Technol 2010; Weiss MA. Vitam Horm 2009]. Dr. Weiss’s work at Case Western focuses primarily on this last approach, with the practical aim of not only producing a more rapid onset of action but also developing a temperaturestable insulin molecule that could be distributed in areas that lack refrigeration, such as in underdeveloped nations. His work using an amino acid linker technology has yielded lead compounds that do not rely on zinc (contrary to other preparations) and are stable over several days at room temperature [Hua QX et al. J Biol Chem 2008]. Investigations that concern these types of compounds are ongoing. Slow-Release Insulin Satish K. Garg, MD, University of Colorado, Denver, CO, reviewed pipeline candidates of slow-release insulin. While acknowledging the currently available treatment options of insulin glargine and insulin detemir as viable choices for long-acting basal coverage, the development of next-generation compounds is necessitated by the need for a “true” 24-hour therapeutic effect with less hypoglycemia and better A1C control and without the potential for weight gain. Novel candidates include degludec, basal insulin therapy, “smart” insulin, and the transdermal insulin patch. Degludec is a recombinant human insulin with a single-base deletion and an added 16-carbon fatty acid moiety. Degludec forms soluble multihexamer assemblies after subcutaneous injection. In the first of three studies that were reported at the American Diabetes Association 70th Annual Scientific Session 2010, degludec demonstrated equivalent duration with less glycemic variation compared with insulin glargine (IGlar) in a euglycemic clamp investigation [Jonassen IB et al. ADA 2010 Abstract #0039]. A second study that compared degludec and IGlar in combination with insulin aspart in type 1 diabetes mellitus (T1DM) patients showed that at 16 weeks, degludec was similar to IGlar with regard to glycemic control. However, degludec demonstrated superiority over IGlar for incidence of hypoglycemia (RR, 0.72; 95% CI, 0.52 to 0.99; n=177) [Luigi F et al. ADA 2010 Abstract #0559-P]. Highlights from the Highlights from the American Diabetes Association 70th Annual Scientific Sessions 33  http://www.lantus.com/ http://www.apidra.com/

Table of Contents for the Digital Edition of MD Conference Express

MD Conference Express
Contents
Real-Time Continuous Glucose Monitoring and Diabetes Treatment
The Globalization of Diabetes
Treat the Individual, Tend to the Population
Microvascular Outcomes from the ACCORD Trial
Diabetic Retinopathy in the ACCORD Trial
Results from the STAR 3 Study
Findings from HELP PD
Insights from the BARI 2D Trial
Effect of Atorvastatin on Beta Cell Function
Caffeine Supplementation Reduces Exercise Induced Hypoglycemia
Cardiometabolic Risk
Point of Care Devides
Newer Insulins
Diabetes, Glycemia and Cardiovascular Disease: Is it Time to Rethink the Regulatory Approach?
Diabetes and Cancer: ADA Consensus Statement
The Diabetic Foot Wound
HEALTHY Study - Middle School-Based Intervention to Reduce Diabetes Risk

MD Conference Express

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