Alogliptin: a new dipeptidyl peptidase-4 inhibitor with potential anti-atherogenic properties

Kutoh, Eiji; Kaneoka, Noriko; Hirate, M.

doi:10.3109/07435800.2014.952743

Cited by 14 publications

(21 citation statements)

References 25 publications

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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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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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“…The final analysis included 33 subjects. Subjects were encouraged to follow previously described exercise and diet regimens [17, 18]. Subjects provided informed consent, and the study protocol was approved by the Ethical Committee/Institutional Review Board of Gyoda General Hospital.…”

Section: Methodsmentioning

confidence: 99%

“…Blood was collected from patients in the fasting state before breakfast, and the standard technique was used to measure these parameters as described previously [18]. HbA 1c and FBG were measured once a month.…”

Section: Methodsmentioning

confidence: 99%

Distinct Glucose-Lowering Mechanisms of Ipragliflozin Depending on Body Weight Changes

Kutoh¹,

Murayama²,

Wada³

et al. 2016

Drugs R D

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BackgroundSodium-glucose co-transporter 2 inhibitors have been shown to reduce body weight. However, little is known about whether a reduction in body weight affects glycemic and non-glycemic parameters.ObjectivesThe aim of this study was to investigate the link between the changes in body weight and those in metabolic parameters in drug-naïve subjects with type 2 diabetes mellitus (T2DM) receiving ipragliflozin monotherapy.MethodsSubjects received ipragliflozin monotherapy 25–50 mg/day for 3 months (n = 33). They were then divided into two groups: group L (‘lost’; n = 17) comprised patients who lost weight (change [Δ] in body mass index [BMI] ≤ −0.75, p < 0.00001), and group N (‘neutral’; n = 16) comprised patients who did not lose weight (ΔBMI > −0.75, not significant [NS]).ResultsIn these two groups, similar reductions were observed in glycated hemoglobin (HbA1c) levels (group L: 9.76–8.02%, p < 0.00001; group N: 10.07–8.36%, p < 0.0005). Homeostasis model assessment (HOMA)-B levels increased in both groups, with inter-group differences (p < 0.05; +38.91 vs. +96.83% in group L and N, respectively). However, some parameters showed distinct regulatory patterns. For instance, in group L, reductions were observed in HOMA-R (−20.18%, p < 0.04) and uric acid (UA; −8.91%, p < 0.02) levels. Correlations were seen between the change in HOMA-R and those in fasting blood glucose (FBG) levels (R = 0.557, p < 0.02). Non-significant increases in free fatty acid (FFA) levels and decreases in non-high-density lipoprotein cholesterol (non-HDL-C) or low-density lipoprotein cholesterol (LDL-C) levels were also noted. In group N, reductions in FFA levels (−17.07%, p < 0.05) were observed, and negative correlations were seen between ΔHOMA-B and ΔFBG (R = −0.4781, p < 0.05) and between Δ FFA and Δ HOMA-B levels (R = −0.4305, p < 0.05). Non-significant increases in non-HDL-C and LDL-C levels were also noted. Inter-group differences existed between group L and group N in the changes in non-HDL-C and LDL-C levels (both p < 0.05).ConclusionsThese results indicate that ipragliflozin may possess distinct dual glucose-lowering mechanisms depending on body weight changes. Degrees of insulin resistance decrease in subjects who lose weight. Conversely, ipragliflozin reduces lipotoxicity (FFA levels), thereby activating beta-cell function, in subjects who do not lose weight. Similar glycemic efficacies were observed in both cases. In patients who lost weight, ipragliflozin was associated with improvements in the levels of metabolic parameters related to cardiovascular risk factors, including UA and atherogenic lipid levels (non-HDL-C and LDL-C) compared with those who did not lose weight.

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“…Increases of BMI with teneligliptin were noted in low HOMA-R group (Table 4). Although it is generally believed that DPP-4 inhibitors are weight neutral, some researchers reported weight gain upon improvements of blood glucose levels and potential mechanisms of bodyweight gain by DPP-4 inhibitors were postulated [27]. It remains to be investigated whether this increase of BMI has any impact on the increased risk of cardiovascular disorders.…”

Section: Baseline Differences and Differential Effects Of Metabolic Pmentioning

confidence: 97%

Teneligliptin, a Chemotype Prolyl-Thiazolidine-Based Novel Dipeptidyl Peptidase-4 Inhibitor with Insulin Sensitizing Properties

Kutoh¹,

Wada²,

Terayama³

2016

Clin Drug Investig

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These results indicate that: (i) teneligliptin ameliorates insulin sensitivity and non-HDL-C levels in subjects with high degrees of insulin resistance. This is not the case with sitagliptin, though similar glycemic efficacies were observed. (ii) glycemic efficacy of teneligliptin may be determined by the balance of its capacity in modulating insulin resistance and beta-cell function depending on the degrees of baseline insulin resistance.

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Alogliptin: a new dipeptidyl peptidase-4 inhibitor with potential anti-atherogenic properties

Cited by 14 publications

References 25 publications

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

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

Distinct Glucose-Lowering Mechanisms of Ipragliflozin Depending on Body Weight Changes

Teneligliptin, a Chemotype Prolyl-Thiazolidine-Based Novel Dipeptidyl Peptidase-4 Inhibitor with Insulin Sensitizing Properties

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