Abstract:
BACKGROUND:Sitagliptin is a highly selective oral dipeptidyl peptidase-4 inhibitor. This drug increases the plasma concentration of active glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide. These two hormones then simulate the secretion of insulin in a glucose-dependent manner and inhibit glucagon secretion, thus reducing circulating glucose levels. In animal models, GLP-1 increases beta-cell mass. OBJECTIVE:To review the efficacy and safety of sitagliptin in combined therapies (as add on or initial combination treatment) in type 2 diabetes. METHODS:A Medline search on published clinical trials involving sitagliptin in combined therapies was performed; additional information from published papers and abstracts to congresses on preclinical and basic science issues was also included to support the mechanistic rationale of combinations. RESULTS/CONCLUSION:In humans sitagliptin administration reduces fasting and postprandial glucose and A1c levels. Sitagliptin is as effective as glipizide (close to 0.7% mean A1c reduction), but has fewer hypoglycemic events than other oral insulin secretagogues. Since metformin reduces hepatic glucose production and increases GLP-1 release, combined therapy with sitagliptin becomes complementary and has been shown to have important additive effects. Sitagliptin combined with pioglitazone resulted in improved metabolic control when compared with pioglitazone plus placebo. Combined administration with insulin requires further studies. The weight neutral effect of sitagliptin, its glucose-dependent action (lower risk of hypoglycemia), the beneficial effects on beta-cell function and its eventual protective action on beta-cell mass makes it an excellent option for monotherapy or combined with metformin, glitazones or even sulfonylurea.
journal_name
Expert Opin Pharmacotherjournal_title
Expert opinion on pharmacotherapyauthors
Gagliardino JJ,Santoro S,Arellano S,Di Girolamo Gdoi
10.1517/14656566.9.9.1495subject
Has Abstractpub_date
2008-06-01 00:00:00pages
1495-507issue
9eissn
1465-6566issn
1744-7666journal_volume
9pub_type
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journal_title:Expert opinion on pharmacotherapy
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