Incretin-based Combination Therapy in Type 2 Diabetes Mellitus

Article information

J Korean Med Assoc. 2009;52(10):1030-1036

Publication date (electronic) : 2009 October 31

doi : https://doi.org/10.5124/jkma.2009.52.10.1030

Division of Endocrinology and Metabolism/Department of Internal Medicine, Sungkyunkwan University School of Medicine, Korea. mslee0923@skku.edu

Abstract

While there are many therapies for type 2 diabetes are available including insulin secretagogues, insulin sensitizers and exogenous insulin, many patients are unable to reach recommended therapeutic targets. Incretin-based therapies have recently been introduced into clinical practice, and these novel therapies may make it possible to achieve improved glycemic control either with no weight gain (dipeptidyl peptidase-4 [DPP-4] inhibitors sitagliptin and vildagliptin, or with weight loss (glucagon-like peptide-1 [GLP-1] mimetics exenatide and liraglutide). This article aims to provide an overview of efficacy and safety data regarding incretin-based clinical trials in type 2 diabetic patients, and propose a systematic approach to treatment including patient selection and optimal treatment combination. In addition, preclinical data suggest that incretin-based therapies may also preserve-cell function. Therefore, these agents hold out promise of a truly disease-modifying therapy that would target the progressive nature of type 2 diabetes. Additional clinical trials will be required to test such hypothesis.

Keywords: DPP-4 inhibitors; GLP-1 mimetics; Incretin; Type 2 diabetes

References

1. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008. 3591577–1589.

2. Gilbert MP, Pratley RE. Efficacy and safety of incretin-based therapies in patients with type 2 diabetes mellitus. Am J Med 2009. 611–24.

3. Kendall DM, Cuddihy RM, Bergenstal RM. Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. Am J Med 2009. 637–50.

4. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B. Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009. 32193–203.

5. Chia CW, Egan JM. Incretin-based therapies in type 2 diabetes mellitus. J Clin Endocrinol Metab 2008. 933703–3716.

Article information Continued

Figure 1

Redefining of pathophysiology of type 2 diabetes. Insulin resistance, β-cell dysfunction, and impaired incretin effects play a significant role in the development and progression of hyperglycemia in type 2 diabetes.