Evolving concepts of type 2 diabetes management with oral medications: new approaches to an old disease.
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, CB(1) 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.
University of California, San Diego, CA, USA. rrhenry@ucsd.edu
Robert R
RR
Henry
D000284:Administration, Oral; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors
D007004:Hypoglycemic Agents; D043884:Receptor, Cannabinoid, CB1