Incretin-Based Therapies for the Treatment of Type 2 Diabetes: Evaluation of the Risks and Benefits

  1. Daniel J. Drucker, MD1,
  2. Steven I. Sherman, MD2,
  3. Fred S. Gorelick, MD3,
  4. Richard M. Bergenstal, MD4,
  5. Robert S. Sherwin, MD3 and
  6. John B. Buse, MD, PHD5
  1. 1Department of Medicine, Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Ontario;
  2. 2The University of Texas M.D. Anderson Cancer Center, Houston, Texas;
  3. 3Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut;
  4. 4International Diabetes Center, Minneapolis, Minnesota;
  5. 5Division of Endocrinology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
  1. Corresponding author: Daniel J. Drucker, d.drucker{at}utoronto.ca.

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.

Figure 1

Relative comparison of properties exhibited by different classes of agents approved for the treatment of type 2 diabetes. CVD, cardiovascular disease; TG, triglycerides; CHF, congestive heart failure. A1C reduction depends on starting A1C.

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 …

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