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Sitagliptin phosphate: a DPP-4 inhibitor for the treatment of type 2 diabetes mellitus.
Clin Ther. 2007 Dec; 29(12):2614-34.CT

Abstract

BACKGROUND

Sitagliptin phosphate, the first dipeptidyl peptidase 4 (DPP-4) inhibitor, provides a new treatment option for patients with type 2 diabetes.

OBJECTIVE

The purpose of this article is to review the pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, and cost of sitagliptin in adults with type 2 diabetes.

METHODS

A literature search of MEDLINE (1966-May 10, 2007), Iowa Drug Information Service (1966-May 10, 2007), and International Pharmaceutical Abstracts (1970-May 10, 2007) was performed using the terms sitagliptin and MK-0431. English-language, original research and review articles were reviewed, as were citations from these articles. The 2005 and 2006 American Diabetes Association Scientific Abstracts were searched, and the US Food and Drug Administration review of the new drug application for sitagliptin and select information from the manufacturer were consulted.

RESULTS

By inhibiting DPP-4, sitagliptin enhances postprandial levels of active glucagon-like peptide-1 (GLP-1), leading to a rise in insulin release and decrease in glucagon secretion from pancreatic alpha-cells. Sitagliptin is 87% orally bioavailable, undergoes minimal hepatic metabolism, and is primarily excreted unchanged (approximately 79%) in the urine. At doses >or=100 mg QD, DPP-4 activity is inhibited by >80%, with a consequent 2-fold rise in active GLP-1 levels. The reduction in glycosylated hemoglobin (HbA(1c)) observed with 100 mg QD of sitagliptin in Phase III monotherapy trials ranged from approximately 0.5% to 0.6% (P <or= 0.001 vs placebo). In Phase III combination trials, HbA(1c) was reduced by approximately 0.7% when added to metformin and approximately 0.9% with pioglitazone (P < 0.001 vs placebo). Markers of beta-cell function, including proinsulin/insulin ratio and homeostasis model assessment of beta-cell function, were improved with sitagliptin treatment. In studies, sitagliptin has been well tolerated; significant hypoglycemia and weight gain have not been noted.

CONCLUSIONS

When used alone or in combination with metformin or pioglitazone, sitagliptin has been associated with significant reductions in HbA(1c) and has been well tolerated. Before its place in therapy can be firmly established, long-term studies evaluating the safety of prolonged DPP-4 inhibition are necessary.

Authors+Show Affiliations

International Drug Information Center, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 Dekalb Avenue, Brooklyn, NY 11201, USA. tina.zerilli@liu.eduNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

18201579

Citation

Zerilli, Tina, and Eunice Y. Pyon. "Sitagliptin Phosphate: a DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus." Clinical Therapeutics, vol. 29, no. 12, 2007, pp. 2614-34.
Zerilli T, Pyon EY. Sitagliptin phosphate: a DPP-4 inhibitor for the treatment of type 2 diabetes mellitus. Clin Ther. 2007;29(12):2614-34.
Zerilli, T., & Pyon, E. Y. (2007). Sitagliptin phosphate: a DPP-4 inhibitor for the treatment of type 2 diabetes mellitus. Clinical Therapeutics, 29(12), 2614-34. https://doi.org/10.1016/j.clinthera.2007.12.034
Zerilli T, Pyon EY. Sitagliptin Phosphate: a DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus. Clin Ther. 2007;29(12):2614-34. PubMed PMID: 18201579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sitagliptin phosphate: a DPP-4 inhibitor for the treatment of type 2 diabetes mellitus. AU - Zerilli,Tina, AU - Pyon,Eunice Y, PY - 2007/9/19/accepted PY - 2008/1/19/pubmed PY - 2008/7/2/medline PY - 2008/1/19/entrez SP - 2614 EP - 34 JF - Clinical therapeutics JO - Clin Ther VL - 29 IS - 12 N2 - BACKGROUND: Sitagliptin phosphate, the first dipeptidyl peptidase 4 (DPP-4) inhibitor, provides a new treatment option for patients with type 2 diabetes. OBJECTIVE: The purpose of this article is to review the pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, and cost of sitagliptin in adults with type 2 diabetes. METHODS: A literature search of MEDLINE (1966-May 10, 2007), Iowa Drug Information Service (1966-May 10, 2007), and International Pharmaceutical Abstracts (1970-May 10, 2007) was performed using the terms sitagliptin and MK-0431. English-language, original research and review articles were reviewed, as were citations from these articles. The 2005 and 2006 American Diabetes Association Scientific Abstracts were searched, and the US Food and Drug Administration review of the new drug application for sitagliptin and select information from the manufacturer were consulted. RESULTS: By inhibiting DPP-4, sitagliptin enhances postprandial levels of active glucagon-like peptide-1 (GLP-1), leading to a rise in insulin release and decrease in glucagon secretion from pancreatic alpha-cells. Sitagliptin is 87% orally bioavailable, undergoes minimal hepatic metabolism, and is primarily excreted unchanged (approximately 79%) in the urine. At doses >or=100 mg QD, DPP-4 activity is inhibited by >80%, with a consequent 2-fold rise in active GLP-1 levels. The reduction in glycosylated hemoglobin (HbA(1c)) observed with 100 mg QD of sitagliptin in Phase III monotherapy trials ranged from approximately 0.5% to 0.6% (P <or= 0.001 vs placebo). In Phase III combination trials, HbA(1c) was reduced by approximately 0.7% when added to metformin and approximately 0.9% with pioglitazone (P < 0.001 vs placebo). Markers of beta-cell function, including proinsulin/insulin ratio and homeostasis model assessment of beta-cell function, were improved with sitagliptin treatment. In studies, sitagliptin has been well tolerated; significant hypoglycemia and weight gain have not been noted. CONCLUSIONS: When used alone or in combination with metformin or pioglitazone, sitagliptin has been associated with significant reductions in HbA(1c) and has been well tolerated. Before its place in therapy can be firmly established, long-term studies evaluating the safety of prolonged DPP-4 inhibition are necessary. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/18201579/Sitagliptin_phosphate:_a_DPP_4_inhibitor_for_the_treatment_of_type_2_diabetes_mellitus_ DB - PRIME DP - Unbound Medicine ER -