Clinical Application of Incretin-Based Therapy: Therapeutic Potential, Patient Selection and Clinical Use  David M. Kendall, MD, Robert M. Cuddihy, MD, Richard M. Bergenstal, MD  The American Journal of Medicine  Volume 122, Issue 6, Pages S37-S50 (June 2009) DOI: 10.1016/j.amjmed.2009.03.015 Copyright © 2009 Terms and Conditions

Figure 1 Postulated role of insulin resistance, β-cell dysfunction, and an impaired incretin effect in the pathogenesis of type 2 diabetes mellitus. (Adapted from J Clin Endocrinol Metab,23Diabetes,24,27Eur J Clin Endocrinol,25 and J Clin Invest.26) The American Journal of Medicine 2009 122, S37-S50DOI: (10.1016/j.amjmed.2009.03.015) Copyright © 2009 Terms and Conditions

Figure 2 Representative depiction of the natural history of type 2 diabetes mellitus highlighting the role of insulin resistance, insulin deficiency, and impaired incretin effect. Both the time course and relative function are descriptive. These 3 core pathophysiologic defects likely combine to contribute to the progressive nature of the disease, and may account for much of the deterioration in glucose control observed clinical in patients with type 2 diabetes. IFG = impaired fasting glucose; IGT = impaired glucose tolerance. For glucose, 1 mg/dL = 0.5551 mmol/L. (Courtesy of the International Diabetes Center © 2008.) The American Journal of Medicine 2009 122, S37-S50DOI: (10.1016/j.amjmed.2009.03.015) Copyright © 2009 Terms and Conditions

Figure 3 International Diabetes Center (IDC) treatment algorithm for the management of type 2 diabetes center. This recommended approach to treatment underscores the central importance of established glycemic targets and the critical role of diabetes self-management education and nutrition and activity counseling. It further underscores the selection of drug therapies based on pathophysiologic characteristics and individual patient characteristics. To convert glucose measurements, 1 mg/dL = 0.5551 mmol/L. CV = cardiovascular; DPP-4 = dipeptidyl peptidase–4; FPG = fasting plasma glucose; GI = gastrointestinal; GLP-1 = glucagonlike peptide–1; OA = oral antidiabetic medication; RPG = random plasma glucose; SMBG = self-monitoring of blood glucose; SU = sulfonylurea; TZD = thiazolidinedione. *Saxagliptin and liraglutide pending US and EU regulatory review at time of this publication. †Limited clinical data for combination therapy with insulin plus either DPP-4 inhibitor or GLP-1 agonist. (Adapted from Diabetes Care,38,39,43,44J Fam Pract,40J Clin Outcomes Manag,41Am J Manag Care,42Staged Diabetes Management: a Systematic Approach,45Endocr Pract,46 and Popul Health Manag.47 Courtesy of the International Diabetes Center © 2009.) The American Journal of Medicine 2009 122, S37-S50DOI: (10.1016/j.amjmed.2009.03.015) Copyright © 2009 Terms and Conditions