Alogliptin plus voglibose in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label, long-term extension.
ABSTRACT To compare the efficacy and safety of alogliptin and placebo as add-on therapy in Japanese patients with type 2 diabetes who experienced inadequate glycemic control on voglibose plus diet/exercise therapy.
During an 8 week screening phase, patients aged ≥ 20 years were stabilized on voglibose 0.2 mg three times daily plus diet/exercise therapy. Those with HbA1c between ≥ 6.9% and <10.4% were randomly assigned to 12 weeks' double-blind treatment with once daily alogliptin 12.5 or 25 mg, or placebo. The primary endpoint was the change in HbA1c at 12 weeks from baseline. Patients then entered an open-label, 40 week extension trial (patients in the placebo group were randomly allocated to alogliptin 12.5 or 25 mg).
www.clinicaltrials.gov ; pivotal trial NCT01263483; Long term trial NCT01263509.
Least square mean change in HbA1c after 12 weeks' therapy from baseline (primary endpoint) was significantly greater in the alogliptin 12.5 mg (-0.96%; P < 0.0001) and 25 mg (-0.93%; P < 0.0001) groups compared with placebo (+0.06%). This was associated with statistically significant improvements in other measures of glycemic control, in particular sustained reductions in fasting plasma glucose and postprandial plasma glucose. These benefits were maintained for the duration of the 1 year study and, importantly, they were achieved without detrimental effects on tolerability/safety. In particular, there was no increase in the rate of hypoglycemia and almost no changes in mean body weight.
Addition of once daily alogliptin to voglibose monotherapy in Japanese patients with uncontrolled type 2 diabetes produced clinically significant improvements in glycemic control, and was well tolerated.
Article: Dipeptidyl peptidase-4 inhibitors attenuate endothelial function as evaluated by flow-mediated vasodilatation in type 2 diabetic patients.[show abstract] [hide abstract]
ABSTRACT: Endothelial dysfunction is an independent predictor for cardiovascular events in patients with type 2 diabetes (T2DM). Glucagon like peptide-1 (GLP-1) reportedly exerts vasodilatory actions, and inhibitors of dipeptidyl peptidase-4 (DPP-4), an enzyme-degrading GLP-1, are widely used to treat T2DM. We therefore hypothesized that DPP-4 inhibitors (DPP-4Is) improve endothelial function in T2DM patients and performed 2 prospective, randomized crossover trials to compare the DPP-4I sitagliptin and an α-glucosidase inhibitor, voglibose (in study 1) and the DPP-4Is sitagliptin and alogliptin (in study 2). In study 1, 24 men with T2DM (46±5 years) were randomized to sitagliptin or voglibose for 6 weeks without washout periods. Surprisingly, sitagliptin significantly reduced flow-mediated vasodilatation (FMD; -51% compared with baseline, P<0.05) of the brachial artery despite improved diabetic status. In contrast, voglibose did not affect FMD. To confirm this result and determine whether it is a class effect, we conducted another trial (study 2) to compare sitagliptin and alogliptin in 42 T2DM patients (66±8 years) for 6 weeks with 4-week washout periods. Both DPP-4Is improved glycemic control but significantly attenuated FMD (7.2/4.3%, P<0.001, before/after sitagliptin; 7.0/4.8%, P<0.001, before/after alogliptin, respectively). Interestingly, FMD reduction was less evident in subjects who were on statins or whose LDL cholesterol levels were reduced by them, but this was not correlated with parameters including DPP-4 activity and GLP-1 levels or diabetic parameters. Our 2 independent trials demonstrated that DPP-4 inhibition attenuated endothelial function as evaluated by FMD in T2DM patients. This unexpected unfavorable effect may be a class effect of DPP-4Is. URL: http://center.umin.ac.jp, Unique Identifiers: UMIN000005682 (sitagliptin versus voglibose) and UMIN000005681 (sitagliptin versus alogliptin).Journal of the American Heart Association. 01/2013; 2(1):e003277.