Evolving concepts of type 2 diabetes management with oral medications: new approaches to an old disease

ABSTRACT

Background: Type 2 diabetes is often accompanied by co-morbid conditions such as hypertension and dyslipidemia, which, coupled with persistent hyperglycemia, result in significant macrovascular and microvascular complications. Type 2 diabetes treatments focus primarily on controlling hyperglycemia, hypertension, and dyslipidemia to stabilize the disease and minimize complications. Despite treatment, control of hyperglycemia and the conditions associated with type 2 diabetes are suboptimal in the majority of patients. Research efforts have concentrated on the development of new therapies for type 2 diabetes, including agents that could be used both as monotherapy and in combination with established oral antidiabetic agents to improve glycemic control and reduce the disease burden on patients.

Objective: To review published literature on oral agents in development for type 2 diabetes, with a focus on their mechanism of action and impact on concomitant risk factors.

Methods: After identifying oral agents in late-stage development for type 2 diabetes using the R&D Insight database, a literature review was conducted through PubMed for studies (preferably randomized, controlled trials) on dipeptidyl peptidase-IV inhibitors, CB₁ cannabinoid receptor blockers, and bile acid sequestrants. Where limited published data were available, abstracts from recent major conferences were searched. Other emerging therapies targeting pathways involved in modifying insulin resistance, glycogenolysis, and gluconeogenesis are also discussed.

Conclusions: A variety of novel therapies for type 2 diabetes are in development, which will provide patients and diabetes care providers more choices for the management of this disease. Importantly, many of these treatments offer the potential to significantly improve multiple metabolic parameters.

Key words: :

• Glucose
• Oral antidiabetic agents
• Type 2 diabetes mellitus

Acknowledgments

Declaration of interest: This Review was funded by the Department of Veteran Affairs, the Veterans Affairs San Diego Healthcare System and Daiichi Sankyo, Inc. RRH has received grant/research support from Bristol Myers-Squibb, Daiichi Sankyo, GlaxoSmithKline, Novartis, Novo Nordisk, Roche, and Takeda; is a consultant/speaker for Bristol Myers-Squibb, Daiichi Sankyo, DiObex, Eli Lilly, GlaxoSmithKline, Novartis, Novo Nordisk, Roche, sanofi-aventis, and Takeda. Editorial assistance for the preparation of this manuscript was provided by Karen Stauffer, PhD of Wolters Kluwer Health and funded by Daiichi Sankyo.