Incretin Mimetics and DPP-IV Inhibitors: New Paradigms for the Treatment of Type 2 Diabetes

Deborah Hinnen; Loretta L. Nielsen; Amy Waninger; Pamela Kushner

doi:10.3122/jabfm.19.6.612

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Table 1.

Pharmacological Treatment Choices for Patients with Type 2 Diabetes

Pharmacologic Treatment Classes	Mechanism of Action	Effects/Characteristics	Adverse Events
Biguanide (metformin)	Decrease hepatic glucose production Decrease intestinal glucose absorption Increase glucose uptake by skeletal muscle and fat	Reduce blood glucose concentration Increase sensitivity to insulin Reduce blood lipid levels Oral administration	Diarrhea Nausea Vomitting May cause lactic acidosis
Sulfonylureas	Stimulate pancreatic β-cell insulin secretion	Reduce blood glucose concentration Lower risk of hypoglycemia than insulin Oral administration	Hypoglycemia Weight gain Nausea Vomiting
Thiazolidinediones	Improve target cell response to insulin Decrease hepatic glucose output Increase insulin-dependent glucose uptake in skeletal muscle and fat	Reduce blood glucose concentration Beneficial alteration of blood lipid levels Possible beneficial effects on pancreas and cardiovascular risk factors Oral administration	Alteration in liver function indicators Anemia Detrimental cardiac effects Edema Weight gain
Meglitinides and d-phenylalanine derivatives	Stimulate glucose-mediated insulin secretion	Reduce blood glucose concentration Reduce postprandial glucose excursions Stimulates insulin secretion Oral administration	Hypoglycemia Diarrhea Weight gain
α-Glucosidase inhibitors	Inhibit pancreatic α-amylase and membrane-bound α-glucosidase enzymes Inhibit intestinal disaccharide metabolism, delaying glucose absorption	Reduce blood glucose concentration Reduce postprandial glucose excursions Level out daytime glucose concentrations Disperse calories over time Weight neutral Oral administration	Abdominal pain Diarrhea Flatulence Possible elevated liver enzymes
Insulin and insulin analogues	Replace/supplement endogenous insulin hormone to correct deficiency	Reduce blood glucose concentration Subcutaneous injection	Hypoglycemia Weight gain
Potential therapeutics discussed in this article
Incretin mimetics: Exenatide (others in clinical testing)	Replace/supplement endogenous incretin hormone(s) glucoregulatory activity Adjunctive therapy with metformin and/or sulfonylureas	Reduce blood glucose concentration Reduce postprandial glucose excursions Enhance glucose-dependent insulin secretion Suppress inappropriately elevated glucagon secretion Reduce food intake Slow gastric emptying Weight reduction or weight neutral Possible beneficial effects on pancreas (preclinical diabetes models) Subcutaneous injection	Nausea Vomiting Increased hypoglycemia when administered with sulfonylureas Awaiting clinical data for combination with other antidiabetic treatments
DPP-IV inhibitors (clinical testing)	Inhibit peptide hormone metabolism by DPP-IV enzyme, thus increasing blood concentations of endogenous, bioactive forms of GLP-1 and other peptides	Reduce blood glucose concentration Reduce postprandial glucose excursions Weight neutral Possible beneficial effects on pancreas and insulin sensitivity (preclinical diabetes models) Oral administration Status of disease progression may impact efficacy	Adverse events data not yet publicly available. Phase 3 clinical trials in progress for full efficacy & safety profile

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Disclosure statements for: Incretin Mimetics and DPP-IV Inhibitors: New Paradigms for the Treatment of Type 2 Diabetes Deborah Hinnen, Loretta L. Nielsen, Amy Waninger, and Pamela Kushner J Am Board Fam Med 2006 19: 612-620

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Disclosure Statements - Disclosure statements for: Incretin Mimetics and DPP-IV Inhibitors: New Paradigms for the Treatment of Type 2 Diabetes. Deborah Hinnen, Loretta L. Nielsen, Amy Waninger, and Pamela Kushner. J Am Board Fam Med 2006;19:612-620