To compare the metabolic responses to 2 insulins demonstrating distinctly different pharmacokinetic profiles, Technosphere® Insulin (TI) inhalation powder and subcutaneous insulin lispro (LIS). TI inhalation powder undergoes ultra-rapid absorption with a correspondingly fast onset and quick rise to peak action with a short duration of effect. LIS is absorbed more slowly with a longer time to peak action and longer duration of glucose-lowering effect.
Methods : Twelve patients with type 2 diabetes underwent 2 mixed-meal tolerance tests after receiving LIS 10 U (n=12) or TI 16 or 24 units (n=6 per dose) in random order in a cross-over design. Endogenous glucose production (EGP) rate and glucose absorption (Ra) and disposal rates (Rd) were derived from tracer data.
With TI, the maximum Rd and maximum EGP suppression occurred 30 to 45 minutes after the start of the meal and coincided with the maximum Ra from the meal. With LIS, pharmacodynamic effects peaked after the maximum Ra.
The mean PPG curves for the 3 treatments demonstrated that TI achieves nearly constant glucose concentrations for 90 minutes after the start of the meal, while PPG significantly rises within the first 30 minutes after administration of LIS. The mean PPG excursion of the group receiving TI 24 units did not exceed 10 mg/dL during the first 90 minutes. In contrast, the PPG excursion after LIS 10 U required less than 20 minutes to reach 10 mg/dL. A dose of TI 16 units controlled PPG excursions below 10 mg/dL for more than 45 minutes. Differences from the LIS-PPG curve were statistically significant from 30 to 60 minutes at the low dose of TI and from 45 to 105 minutes at the higher dose of TI. The tight control of early PPG results from the agreement in timing of TI’s insulin-induced glucose demand and glucose absorption from a mixed meal. The duration of PPG control is dose dependent. Consistent with its short duration of effect, PPG started to rise approximately 120 minutes after dosing, but TI’s rapid clearance suggests a small supplemental dose may be taken at that time to extend control with little risk of late postprandial hypoglycemia.
Conclusion : These studies confirm that TI, with its well-timed, insulin-mediated glucose disposal and suppression of EGP, can handle early absorption of glucose during mixed meals.
David Kendall– Chief Medical Officer, MannKind Corporation, Westlake Village, CA, California
Marshall Grant– Senior Director, Clinical Pharmacology, MannKind Corporation, Westlake Village, CA
Rich Bergenstal– Executive Director, International Diabetes Center, Park Nicollet, Minneapolis, MN
Anne Peters– Director, USC Clinical Diabetes Programs, Keck School of Medicine, University of Southern California, Los Angeles, CA
Frank Pompilio– Vice President, Medical Affairs, MannKind Corporation, Westlake Village, CA, Westlake Village, California
Simon Bruce– Clinical Development, Kinexum Services LLC, San Diego, CA
Chief Medical Officer
MannKind Corporation, Westlake Village, CA, California
David Kendall (MD) is the Chief Medical Officer for MannKind Corporation. Dr. Kendall’s career includes over 30 years of experience in diabetes and metabolism research, clinical management, research, and policy advocacy. Dr. Kendall received his MD at the University of Minnesota and earned a BA in Biology from St. Olaf College.
Senior Director, Clinical Pharmacology
MannKind Corporation, Westlake Village, CA
Marshall Grant (PhD, MSc) is the Senior Director of Clinical Pharmacology. Dr. Grant obtained his PhD in Chemical Engineering from Princeton University, and later his MSc in Pharmacokinetic Modeling and Simulation from the University of Manchester.
Executive Director, International Diabetes Center
Park Nicollet, Minneapolis, MN
Rich Bergenstal (MD) is the Executive Director of the International Diabetes Center at Park Nicollet. Dr. Bergenstal is also the former President of Medicine and Science for the American Diabetes Association. He obtained his MD at the University of Chicago.
Director, USC Clinical Diabetes Programs
Keck School of Medicine, University of Southern California, Los Angeles, CA
I am a Professor of Medicine at the Keck School of Medicine of the University of Southern California, Director of the USC Clinical Diabetes Programs and Director and physician for the USC Westside Center for Diabetes.
Vice President, Medical Affairs
MannKind Corporation, Westlake Village, CA
Westlake Village, California
Frank Pompilio (PharmD) is the Vice President of Medical Affairs for MannKind Corporation. Dr. Pompilio has over 25 years experience in healthcare, pharmaceutical, and biotechnology industries. Dr. Pompilio holds a Bachelor of Science in Pharmacology from University of California, Santa Barbara and a Doctorate in Pharmacy from the University of Southern California. He completed a post-graduate residency at the University of Arizona. Following his residency he spent five years as an Assistant Professor of Clinical Pharmacy at the University of Southern California School of Pharmacy where he practiced as a surgical intensive care pharmacist and educator. He has held positions with Kythera Biopharmaceuticals, Allergan, Amgen, and Bristol-Myers Squibb in the areas of Medical Communications, Medical Information, and Medical Science Liaison functions focused on the synthesis and communication of clinical and scientific data to engage and educate the healthcare community with the goal of optimizing patient care.
Kinexum Services LLC, San Diego, CA
Simon Bruce (MD) is a Clinical Development consultant with Kinexum Services, LLC with nearly 20 years of experience within large pharmaceutical companies and small to medium sized biotech companies alike. Dr. Bruce obtained his MD at the University of Texas Southwestern, completed his residency at the University of Minnesota, was trained in Internal Medicine with a sub-specialization in Endocrinology at the National Institutes of Health, and obtained his BSc from Yale University.