Dipeptidyl Peptidase-4 (DPP-4) 억제제
Dipeptidyl Peptidase-4 Inhibitor
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초록
Recent advances in incretin biology have led to the development of a new class of oral anti-diabetic drugs. To date, there are twoknown incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), of which theformer is a more important therapeutic target for type 2 diabetes. GLP-1 is secreted by intestinal L-cells in response to oral nutrientintake, and it stimulates insulin secretion and suppresses glucagon secretion in a glucose-dependent manner. However, both GLP-1and GIP are rapidly degraded by dipeptidyl peptidase-4 (DPP-4), a multifunctional type II transmembrane glycoprotein. Thus,several DPP-4 inhibitors with different pharmacologic features are now available and can be used either as monotherapy or incombination with other anti-diabetic agents for the treatment of type 2 diabetes. In both therapeutic regimens, DPP-4 inhibitorshave been shown to reduce hemoglobin A1c levels by approximately 0.5-0.8%. In clinical trials, DPP-4 inhibitors were generallywell-tolerated, posed a low risk of hypoglycemia, and did not increase body weight. Despite some reports of a possible increasedrisk of pancreatitis with GLP-1 receptor agonists and DPP-4 inhibitors, no causal associations have been found. Recent randomizedcontrolled clinical trials have shown that DPP-4 inhibitors did not increase or decrease the rates of major adverse cardiovascularevents in patients with type 2 diabetes at high risk of cardiovascular disease, even though this class of anti-diabetic agents hadvarious salutary effects in many studies involving animals or healthy and diabetic humans. Additional studies will be required toresolve these disparate conclusions.
Abstract
Recent advances in incretin biology have led to the development of a new class of oral anti-diabetic drugs. To date, there are twoknown incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), of which theformer is a more important therapeutic target for type 2 diabetes. GLP-1 is secreted by intestinal L-cells in response to oral nutrientintake, and it stimulates insulin secretion and suppresses glucagon secretion in a glucose-dependent manner. However, both GLP-1and GIP are rapidly degraded by dipeptidyl peptidase-4 (DPP-4), a multifunctional type II transmembrane glycoprotein. Thus,several DPP-4 inhibitors with different pharmacologic features are now available and can be used either as monotherapy or incombination with other anti-diabetic agents for the treatment of type 2 diabetes. In both therapeutic regimens, DPP-4 inhibitorshave been shown to reduce hemoglobin A1c levels by approximately 0.5-0.8%. In clinical trials, DPP-4 inhibitors were generallywell-tolerated, posed a low risk of hypoglycemia, and did not increase body weight. Despite some reports of a possible increasedrisk of pancreatitis with GLP-1 receptor agonists and DPP-4 inhibitors, no causal associations have been found. Recent randomizedcontrolled clinical trials have shown that DPP-4 inhibitors did not increase or decrease the rates of major adverse cardiovascularevents in patients with type 2 diabetes at high risk of cardiovascular disease, even though this class of anti-diabetic agents hadvarious salutary effects in many studies involving animals or healthy and diabetic humans. Additional studies will be required toresolve these disparate conclusions.
참고문헌 (36)
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