Background: Progressive beta-cell dysfunction and beta-cell failure are fundamental pathogenic consequences of type 2 diabetes. Dipeptidyl peptidase-IV inhibitors may exhibit improvement on preclinical measures of both beta-cell function, homeostasis model assessment of beta-cell (HOMA-beta) index, and beta-cell dysfunction, proinsulin/insulin ratio (PI/IR), correlating to beta-cell survival.
Research design and methods: A systematic literature search through July 2008 was conducted to extract a consensus of randomized, controlled trials of sitagliptin therapy on measures of beta-cell function. A random-effects model meta-analysis evaluated effects on HOMA-beta and PI/IR versus placebo. Several subgroup analyses, including active control, were conducted. Studies were included if they met the following criteria: (1) randomized trials on sitagliptin; (2) placebo or active control; and (3) data reported on HOMA-beta or PI/IR.
Results: A total of 11 trials (n = 3039) reported effects on HOMA-beta and 8 trials (n = 2325) on PI/IR versus placebo. Four trials (n = 1425) were included in the active control subgroup analysis. Sitagliptin significantly improved HOMA-beta index by 12.03% [95% confidence interval (CI), 9.45-14.60] versus placebo. Sitagliptin also significantly decreased PI/IR -0.06 (95% CI, -0.08 to -0.04). Sitagliptin was inferior to active control for HOMA-beta index [5.64% (95% CI, 0.38-10.90)], but not different in terms of PI/IR [0.01 (95% CI, -0.04 to 0.06)].
Conclusions: Despite significant improvement in HOMA-beta index and PI/IR from placebo, there does not seem to be a benefit of dipeptidyl peptidase-IV inhibitors over other agents with respect to beta-cell function/activity. Long-term prevention of beta-cell dysfunction cannot be ruled out.