Clinical InvestigationImpact of Sitagliptin on Markers of β-cell Function: A Meta-Analysis
Section snippets
Study Selection
A systematic literature search of MEDLINE from 1966 through July 2008; EMBASE from 1990 through July 2008; and the Cochrane Database to identify randomized clinical trials of sitagliptin utilization with a primary or secondary endpoint of HOMA-β or PI/IR was conducted. A search strategy using the MeSH and text keywords MK-431 and sitagliptin was utilized. A manual search of abstracts presented between 2003 and 2007 at the American Diabetes Association Scientific Sessions was conducted. In
RESULTS
Study selection process is described in Figure 1. Of 201 screened articles and abstracts, 150 relevant articles and abstracts were identified, 43 were retrieved for detailed evaluation, and 12 met inclusion criteria. Eleven studies24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34. (n = 3039) for HOMA-β and 8 studies26., 27., 28., 29., 30., 31., 32., 33. (n = 2325) for PI/IR provided data adequate for meta-analysis in the primary cohort (Table 2). Four studies (n = 1425) were included in the
DISCUSSION
Although some studies did not demonstrate a significant difference versus placebo in HOMA-β26., 31. or PI/IR,30., 33. the totality of data demonstrates a statistically significant improvement in both HOMA-β and PI/IR favoring sitagliptin. The Cardiovascular Health Study indicates that controlling for insulin sensitivity, a 20% decrease in HOMA-β is associated with a 9% increase in both the odds of incident coronary heart disease and 6-year all-cause mortality.36 Although HOMA-β is a significant
CONCLUSIONS
DPP-IV inhibitors seem to benefit short-term surrogate measures of β-cell function (HOMA-β) and dysfunction (PI/IR) versus placebo; thereby representing an agent for early intervention to lower the burden of type 2 diabetes. This effect may be particularly useful in combination with an agent that addresses additional mechanisms of β-cell destruction (TZD) or provides complementary augmentation of GLP-1 (metformin).41., 47. Despite significant improvement in HOMA-β index and PI/IR from placebo,
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2011, Clinical TherapeuticsCitation Excerpt :Sitagliptin was associated with significant improvements in HOMA-B and/or proinsulin:insulin ratios compared with placebo or an active comparator in several randomized, controlled studies.140-148 A meta-analysis of randomized, controlled trials of sitagliptin found significant improvement versus placebo in HOMA-B (+12.03%; 95% CI, 9.45–14.60) and proinsulin:insulin ratio (–0.06; 95% CI: –0.08 to –0.04) with the drug.162 However, effects on HOMA-B were statistically greater with the active comparators compared with sitagliptin (+5.64% with the active comparators; 95% CI, 0.38–10.90) and statistically similar proinsulin:insulin ratio (+0.01 with the active comparators; 95% CI, –0.04 to 0.06).
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2011, American Journal of MedicineCitation Excerpt :Sitagliptin has been shown to improve both HOMA-B and proinsulin–insulin ratio.156–162,168,169 In a meta-analysis of randomized controlled trials, while sitagliptin was superior to placebo in improving HOMA-B and proinsulin–insulin ratio, it was significantly inferior to active comparators regarding HOMA-B and statistically similar to active comparators regarding proinsulin–insulin ratio.175 Vildagliptin has been shown to improve insulin secretory rate,165,166,172 and saxagliptin has been shown to improve HOMA-2β.164,170
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2022, Frontiers in Endocrinology
Dr. East has received research funding from Abbott and Novo Nordisk. Dr. East is on the Speaker’s Bureau for Pfizer and Sankyo-Daiichi. Dr. Riche is on the Speaker’s Bureau for Pfizer.
Abstract was presented at the American College of Clinical Pharmacy Annual Meeting on October 15, 2007.