Incretin-Based Therapies for the Treatment of Type 2 Diabetes: Evaluation of the Risks and Benefits
- Daniel J. Drucker, MD1,
- Steven I. Sherman, MD2,
- Fred S. Gorelick, MD3,
- Richard M. Bergenstal, MD4,
- Robert S. Sherwin, MD3 and
- John B. Buse, MD, PHD5
- 1Department of Medicine, Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Ontario;
- 2The University of Texas M.D. Anderson Cancer Center, Houston, Texas;
- 3Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut;
- 4International Diabetes Center, Minneapolis, Minnesota;
- 5Division of Endocrinology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
- Corresponding author: Daniel J. Drucker, .
Type 2 diabetes is a complex metabolic disorder characterized by hyperglycemia arising from a combination of insufficient insulin secretion together with resistance to insulin action. The incidence and prevalence of type 2 diabetes are rising steadily, fuelled in part by a concomitant increase in the worldwide rates of obesity. As longitudinal studies of type 2 diabetes provide evidence linking improved glycemic control with a reduction in the rates of diabetes-associated complications, there is considerable interest in the therapy of type 2 diabetes (Fig. 1), with a focus on the development and use of new agents that exhibit improved efficacy and safety relative to current available medicines.
Although the number of patients with type 2 diabetes that successfully achieve target levels of A1C is steadily improving, a substantial number of subjects continue to fall short of acceptable treatment goals, leaving them at high risk for development of diabetes-associated complications (1). More importantly, a large number of subjects with type 2 diabetes fail to achieve target values for glucose, lipids, and blood pressure, with only 12.2% of patients meeting target values despite recent improvements in therapeutic agents targeting hyperglycemia, dyslipidemia, and hypertension (2). The development of multiple new agents for the treatment of type 2 diabetes has broadened the options for patient-specific therapy. However, no currently available agents exhibit the ideal profile of exceptional glucose-lowering efficacy to safely achieve target levels of glycemia in a broad range of patients. Hence, highly efficacious agents that exhibit unimpeachable safety, excellent tolerability, and ease of administration to ensure long-term adherence and that also clearly reduce common comorbidities and complications of diabetes are …