Anagliptin in the treatment of type 2 diabetes: safety, efficacy, and patient acceptability

Abstract

Anagliptin is a novel dipeptidyl peptidase-4 inhibitor that has been available in Japan since 2012. Because anagliptin is not generally used in countries other than Japan, there are only a small number of reports investigating the effects of anagliptin. In the present article, we review the safety and efficacy of anagliptin according to data obtained from preclinical trials and postmarketing studies. The usual dose of anagliptin is 200 mg daily, and increases in the dose up to 400 mg daily have been approved in cases in which the blood glucose–lowering effect is insufficient. In a Phase II trial, the reduction in the HbA1c values from baseline after 12 weeks monotherapy with 200 mg and 400 mg of daily anagliptin was 0.75%±0.50% and 0.82%±0.46%, respectively, and more than 40% of the subjects receiving anagliptin at a dose of 200 mg or 400 mg daily achieved an HbA1c level below 6.9%. Furthermore, the levels of HbA1c, fasting blood glucose, and postprandial blood glucose were significantly decreased at 52 weeks compared with the baseline values in a Phase III trial investigating the effects of anagliptin included in combination therapy with other oral antidiabetic agents. In a pooled analysis of Phase II and Phase II/III trials, the goal achievement rates for an HbA1c level below 7.0% at 12 weeks were 40.3%, 39.4%, 30.0%, and 34.8% in the patients treated with anagliptin combined with α-glucosidase inhibitors, thiazolidinediones, sulfonylureas, and biguanides, respectively. Meanwhile, the serum lipid concentrations significantly improved after the administration of anagliptin in a pooled analysis of Phase III trials, and no serious adverse effects have been reported in preclinical trials. Therefore, the use of anagliptin in patients with type 2 diabetes is considered to be safe and effective for both monotherapy and combination therapy.

Anagliptin ameliorates albuminuria and urinary liver-type fatty acid-binding protein excretion in patients with type 2 diabetes with nephropathy in a glucose-lowering-independent manner

“…However, switching to anagliptin from other DPP-4 inhibitors such as sitagliptin, alogliptin, vildagliptin, linagliptin or teneligliptin exhibited no significant change in HbA1c levels after 12 and 24 weeks of treatment with anagliptin in 20 participants. In addition to the glucose-lowering effect, previous reports have shown that anagliptin has a lipid-lowering effect, decreasing the plasma total cholesterol, LDL-C and TG levels, which was indicated by pooled analysis of phase III clinical trials 30. However, in this study, administration of anagliptin showed no change in lipid data after both 12 and 24 weeks of treatment.…”

Dipeptidyl dipeptidase-4 inhibitor, MK-0626, promotes bone marrow-derived endothelial progenitor cell bioactivities for vascular regeneration in diet-induced obese mice

“…Our ex vivo data revealed that proportion of primitive EPCs was higher than definitive EPCs in PB and BM in DIO mice, indicating that obesity-induced inflammatory milieu decrease stem/progenitor cell differentiation in ischemic tissue due to unproductive inflammation, which supports other studies [23,30,31]. The DPP-4 inhibitors, such as Sitagliptin [32], Vildagliptin [33], Linagliptin [34], Teneligliptin [35], Anagliptin [36], Trelagliptin [37], and Omarigliptin [38] are already in use for clinical treatment of diabetes.…”

DPP4 in diabetes

“…In patients with renal impairment, which is a very common complication of T2DM, sitagliptin is more suitable than sulfonylureas ( 100 ). Anagliptin, which is only approved since 2012 in the Japanese market, seems to have serum lipid-lowering and anti-atherogenic actions as well, which makes it unique among the gliptins approved so far ( 101 , 102 ). Anagliptin has an IC50 of 3.3 nM and its main excretion route is renal elimination ( 101 , 103 ).…”