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Published on: April 20, 2017
Insulinotropic meglitinide analogues
1Department of Metabolic Medicine, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, Du Cane Road, W12 0NN, London, UK. a.dornhorst@ic.ac.uk
Abstract:
The loss of early-phase insulin secretion is an important and early event in the natural history of type 2 diabetes. Because a normal pattern of insulin secretion is essential for the effective control of postprandial metabolism, a rational basis for the development of agents that target early-phase insulin release exists. Conventional oral hypoglycaemic agents do not target, or adequately control, postprandial glycaemia. The emergence of new classes of oral agent with a more specific mode of action provides, for the first time, an opportunity to restore early-phase insulin release. One such drug class is the meglitinide analogues (repaglinide, nateglinide, and mitiglinide). These drugs are ideally suited for combination use with metformin. They could also prove effective in combination with a thiazolidinedione, a drug class that targets insulin resistance. Exogenous insulin is frequently required in the late management of type 2 diabetes. However, one hope for newer combinations of diabetic drugs is that the functional life of the beta cell can be extended, thereby delaying the need for insulin injections.
Insights
Loss of early insulin secretion is key in type 2 diabetes. New meglitinide drugs can restore this, potentially delaying the need for insulin therapy.
Area of Science:
- Endocrinology
- Pharmacology
- Metabolic Diseases
Background:
- Early-phase insulin secretion is crucial for managing postprandial metabolism.
- Type 2 diabetes is characterized by the loss of this early insulin release.
- Conventional oral hypoglycemic agents inadequately control postprandial glucose levels.
Purpose of the Study:
- To explore the rationale for developing agents targeting early-phase insulin release.
- To introduce meglitinide analogues as a novel therapeutic class for type 2 diabetes.
- To discuss the potential of these agents in combination therapies.
Main Methods:
- Review of existing literature on type 2 diabetes pathophysiology and treatment.
- Analysis of the mechanism of action of meglitinide analogues.
- Evaluation of potential combination therapies with metformin and thiazolidinediones.
Main Results:
- Meglitinide analogues (repaglinide, nateglinide, mitiglinide) can restore early-phase insulin release.
- These agents are suitable for combination with metformin.
- Potential efficacy in combination with thiazolidinediones, which address insulin resistance.
Conclusions:
- Newer oral agents, specifically meglitinides, offer a targeted approach to restoring early insulin secretion.
- Combination therapies involving meglitinides may improve glycemic control and potentially extend beta-cell function.
- The goal is to delay the eventual need for exogenous insulin in type 2 diabetes management.
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