Endocrino

Pharmacokinetics and pharmacodynamics of insulin analogs in special populations with type 2 diabetes mellitus

Candis M Morello1,2
1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego
2School of Pharmacy, University of California San Francisco, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
Correspondence: Candis M Morello, PharmD,Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, MC 0657, La Jolla, CA 92093-0657, USA, Tel +1 858 822 5586, Fax +1 858 822 5591, Email candismorello@ucsd.edu
This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly citeAbstract
Introduction
The goal of insulin therapy in patientswith either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) is to match as closely as possible normal physiologic insulin secretion to control fasting and postprandial plasma glucose. Modifications of the insulin molecule have resulted in two long-acting insulin analogs (glargine and detemir) and three rapid-acting insulins (aspart, lispro, and glulisine) with improvedpharmacokinetic/pharmacodynamic (PK/PD) profiles. These agents can be used together in basal-bolus therapy to more closely mimic physiologic insulin secretion patterns.
Methods
This study reviews effects of the multiple demographic and clinical parameters in the insulin analogs glargine, detemir, lispro, aspart, and glulisine in patients with T2DM. A search was conducted on PubMed for each major topicconsidered (effects of injection site, age, race/ethnicity, obesity, renal or hepatic dysfunction, pregnancy, exercise, drug interactions) using the topic words and name of each type of insulin analog. Information was also obtained from the prescribing information for each insulin analog.
Results
The PK/PD profiles for insulin analogs may be influenced by many variables including age, weight, andhepatic and renal function. However, these variables do not have equivalent effects on all long-acting or rapid-acting insulin analogs.
Conclusion
Rapid-acting and long-acting insulin analogs represent major advances in treatment for patients with T2DM who require insulin therapy. However, there are potentially important PK and PD differences between the two long-acting agents and among thethree rapid-acting insulin analogs, which should be considered when designing treatment regimens for special patient groups.
Keywords: insulin analogs, type 2 diabetes mellitus, pharmacodynamics, pharmacokinetics
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Introduction
Type 2 diabetes mellitus (T2DM) is characterized by a marked and progressive disruption of normal physiologic insulin secretion. There are two keyaspects of insulin secretion in healthy individuals: (1) basal insulin secretion by pancreatic β cells that occurs continuously to maintain steady glucose levels for extended periods between meals, and (2) prandial secretion in which insulin is rapidly released in an initial first-phase spike in response to a meal, followed by prolonged insulin secretion that returns to basal levels after 2–3 hours(Figure 1).1–3 Insulin is a potent anabolic hormone that binds to insulin receptors to lower blood glucose by facilitating cellular uptake of glucose, amino acids, and fatty acids into skeletal muscle and fat and by inhibiting the output of glucose from the liver. Insulin increases the expression or activity of enzymes that catalyze glycogen, lipid, and protein synthesis, while inhibiting lipolysisand, proteolysis (Figure 2).4,5 In normal healthy individuals, physiologic basal and prandial insulin secretions maintain euglycemia, which affects fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) concentrations.
| Figure 1Mean 24-hour physiologic serum insulin and plasma glucose levels in nondiabetic subjects.3 |
| Figure 2The regulation of metabolism by insulin.5 |...