Alogliptin; A Review of a New Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for the Treatment of Type 2 Diabetes Mellitus

Said, Sarmad; Nwosu, Azikiwe C.; Mukherjee, Debabrata; Hernandez, German T.

doi:10.2174/1871529x14666140701095849

Cited by 12 publications

(8 citation statements)

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“…the base study appear to be generally comparable to those reported in studies of the presently marketed daily DPP-4 inhibitors (2)(3)(4)(5)(6). In the case of 2-h PMG, the incorporation of a study design in which the MTT was always performed at trough (day 7) supports the concept that the degree of DPP-4 inhibition observed at trough with the 25-mg dose is sufficient for maximal clinical efficacy.…”

Section: Discussionsupporting

confidence: 74%

Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4 Inhibitor for the Treatment of Patients With Type 2 Diabetes

et al. 2015

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OBJECTIVEThis study was conducted to determine the optimal dose of omarigliptin, a onceweekly (q.w.) dipeptidyl peptidase IV (DPP-4) inhibitor, for the treatment of patients with type 2 diabetes and evaluate the long-term safety of that dose. RESEARCH DESIGN AND METHODSIn a multicenter, double-blind, 12-week, dose-range finding study, 685 oral antihyperglycemic agent-naïve or washed-out subjects with type 2 diabetes were randomized to one of five once-weekly doses of omarigliptin (0.25 mg, 1 mg, 3 mg, 10 mg, or 25 mg) or placebo. The primary efficacy end point was change from baseline in HbA 1c , and secondary end points were 2-h postmeal glucose (PMG) and fasting plasma glucose (FPG). Analysis included all patients who received at least one dose of the study medication. Subjects who completed the base study were eligible to enter a 66-week extension study. RESULTSOnce-weekly treatment for 12 weeks with omarigliptin provided dose-related reductions in HbA 1c , 2-h PMG, and FPG. At week 12, the omarigliptin 25-mg dose provided the greatest glycemic efficacy. The placebo-adjusted least-squares mean reductions from baseline in HbA 1c , 2-h PMG, and FPG were 20.72% (27.8 mmol/mol), 22.5, and 21.3 mmol/L, respectively (all P < 0.001). The incidence of adverse events was similar across dose groups, with a low incidence of symptomatic hypoglycemia and no effect on body weight. Omarigliptin was generally well-tolerated throughout the base and extension studies. CONCLUSIONSOmarigliptin 25 mg q.w., compared with placebo, provided significant glucose lowering and was generally well tolerated for up to 78 weeks in patients with type 2 diabetes.Dipeptidyl peptidase IV (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes by prolonging the half-life of incretin peptides, which stimulate insulin secretion and decrease glucagon release in a glucose-dependent manner (1). Studies with daily DPP-4 inhibitors have demonstrated a good efficacy, safety, and tolerability profile as monotherapy and as an add-on to other antihyperglycemic agents (AHAs) (2-6). Omarigliptin (MK-3102) is a potent, selective, oral DPP-4 inhibitor with a half-life that supports once-weekly dosing (7). Availability of a once-weekly administered oral

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Section: Discussionsupporting

confidence: 74%

Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4 Inhibitor for the Treatment of Patients With Type 2 Diabetes

et al. 2015

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“…For detailed clinical pharmacology of alogliptin, please read recent reviews about this drug. 38,[41][42][43][44][45][46][47][48][49] Alogliptin as monotherapy or added to metformin, [50][51][52] pioglitazone, [53][54][55][56] glipizide, 57,58 glyburide/glibenclamide, 59 voglibose, [60][61][62] miglitol, 62 acarbose, 63 or insulin 64,65 significantly improves glycaemic control compared with placebo or active comparators in adult or elderly patients with inadequately controlled T2DM. This is associated with good gastrointestinal tolerability and a low incidence of hypoglycaemia.…”

Section: Dpp-4 Inhibitors In Diabetes Treatmentmentioning

confidence: 99%

Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

Chen

Zhou

et al. 2015

Clin Exp Pharma Physio

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SUMMARYDipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral antidiabetic drugs that improve glycaemic control without causing weight gain or increasing hypoglycaemic risk in patients with type 2 diabetes mellitus (T2DM). The eight available DPP-4 inhibitors, including alogliptin, anagliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin, are small molecules used orally with identical mechanism of action and similar safety profiles in patients with T2DM. DPP-4 inhibitors may be used as monotherapy or in double or triple combination with other oral glucoselowering agents such as metformin, thiazolidinediones, or sulfonylureas. Although DPP-4 inhibitors have the same mode of action, they differ by some important pharmacokinetic and pharmacodynamic properties that may be clinically relevant in some patients. The main differences between the eight gliptins include: potency, target selectivity, oral bioavailability, elimination half-life, binding to plasma proteins, metabolic pathways, formation of active metabolite(s), main excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug-drug interactions. The off-target inhibition of selective DPP-4 inhibitors is responsible for multiorgan toxicities such as immune dysfunction, impaired healing, and skin reactions. As a drug class, the DPP-4 inhibitors have become accepted in clinical practice due to their excellent tolerability profile, with a low risk of hypoglycaemia, a neutral effect on body weight, and once-daily dosing. It is unknown if DPP-4 inhibitors can prevent disease progression. More clinical studies are needed to validate the optimal regimens of DPP-4 inhibitors for the management of T2DM when their potential toxicities are closely monitored.

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“…This article aims to update our knowledge on the clinical pharmacology of alogliptin used for the treatment of T2DM, with a focus on clinical pharmacodynamics and pharmacokinetics, adverse effects, drug interactions and future directions. For detailed clinical pharmacology of alogliptin, please read recent reviews about this drug …”

Section: Introductionmentioning

confidence: 99%

“…For detailed clinical pharmacology of alogliptin, please read recent reviews about this drug. 19,[21][22][23][24][25][26][27][28][29]…”

Section: Introductionmentioning

confidence: 99%

An update on the clinical pharmacology of the dipeptidyl peptidase 4 inhibitor alogliptin used for the treatment of type 2 diabetes mellitus

Chen

Zhou

et al. 2015

Clin Exp Pharma Physio

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SUMMARYAlogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor that is a class of relatively new oral hypoglycaemic drugs used in patients with type 2 diabetes (T2DM), can be used as monotherapy or in combination with other anti-diabetic agents, including metformin, pioglitazone, sulfonylureas and insulin with a considerable therapeutic effect. Alogliptin exhibits favorable pharmacokinetic and pharmacodynamic profiles in humans. Alogliptin is mainly metabolized by cytochrome P450 (CYP2D6) and CYP3A4. Dose reduction is recommended for patients with moderate or worse renal impairment. Side effects of alogliptin include nasopharyngitis, upper-respiratory tract infections and headache. Hypoglycaemia is seen in about 1.5% of the T2DM patients. Rare but severe adverse reactions such as acute pancreatitis, serious hypersensitivity including anaphylaxis, angioedema and severe cutaneous reactions such as Stevens-Johnson syndrome have been reported from post-marketing monitoring. Pharmacokinetic interactions have not been observed between alogliptin and other drugs including glyburide, metformin, pioglitazone, insulin and warfarin. The present review aimed to update the clinical information on pharmacodynamics, pharmacokinetics, adverse effects and drug interactions, and to discuss the future directions of alogliptin.

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Alogliptin; A Review of a New Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for the Treatment of Type 2 Diabetes Mellitus

Cited by 12 publications

References 0 publications

Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4 Inhibitor for the Treatment of Patients With Type 2 Diabetes

Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4 Inhibitor for the Treatment of Patients With Type 2 Diabetes

Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

An update on the clinical pharmacology of the dipeptidyl peptidase 4 inhibitor alogliptin used for the treatment of type 2 diabetes mellitus

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