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

Abstract

Introduction: The goal of insulin therapy in patients with 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 improved pharmacokinetic/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 topic considered (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, and hepatic 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 the three rapid-acting insulin analogs, which should be considered when designing treatment regimens for special patient groups.

Keywords: insulin analogs; pharmacodynamics; pharmacokinetics; type 2 diabetes mellitus.

Figure 1

Mean 24-hour physiologic serum insulin and plasma glucose levels in nondiabetic subjects. Reprinted from Am J Med, vol. 113, issue 4, Gerich, Novel insulins: expanding options in diabetes management, pp. 308–316, Copyright (2002), with permission from Elsevier.

Figure 2

The regulation of metabolism by insulin. Reprinted from Nature, vol. 414, issue 6865, Saltiel and Kahn, Insulin signalling and the regulation of glucose and lipid metabolism, pp. 799–806, Copyright (2001), with permission from Nature Publishing Group. Abbreviation: FFA, free fatty acids.