Efficacy and safety of sitagliptin monotherapy and combination therapy in Japanese type 2 diabetes patients

Kubota, Akira; Maeda, Hitoshi; Kanamori, Akira; Matoba, Kiyokazu; Jin, Yasuyuki; Minagawa, Fuyuki; Obana, Mitsuo; Iemitsu, Kotaro; Ito, Shogo; Amamiya, Hikaru; Kaneshiro, Mizuki; Takai, Masahiko; Kaneshige, Hideaki; Hoshino, Kazuhiko; Ishikawa, Masashi; Minami, Nobuaki; Takuma, Tetsuro; Sasai, Nobuo; Aoyagi, Sachio; Kawata, Takehiro; Mokubo, Atsuko; Takeda, Hiroshi; Honda, Shinichi; Machimura, Hideo; Motomiya, Tetsuya; Waseda, Manabu; Naka, Yoshifumi; Tanaka, Yasushi; Terauchi, Yasuo; Matsuba, Ikuro

doi:10.1111/j.2040-1124.2012.00221.x

Cited by 40 publications

(36 citation statements)

References 31 publications

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“…It has been reported (17,18) that combination therapies of DPP-4 inhibitors and sulfonylureas are often used for glycemic control in type 2 diabetes, but cause hypoglycemia in some cases. The incidence rate of hypoglycemia for DPP-4 inhibitors combined with gliclazide is lower than that for combination with glibenclamide or glimepiride (19).…”

Section: Discussionmentioning

confidence: 99%

Role of Epac2A/Rap1 Signaling in Interplay Between Incretin and Sulfonylurea in Insulin Secretion

et al. 2014

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Incretin-related drugs and sulfonylureas are currently used worldwide for the treatment of type 2 diabetes. We recently found that Epac2A, a cAMP binding protein having guanine nucleotide exchange activity toward Rap, is a target of both incretin and sulfonylurea. This suggests the possibility of interplay between incretin and sulfonylurea through Epac2A/Rap1 signaling in insulin secretion. In this study, we examined the combinatorial effects of incretin and various sulfonylureas on insulin secretion and activation of Epac2A/Rap1 signaling. A strong augmentation of insulin secretion by combination of GLP-1 and glibenclamide or glimepiride, which was found in Epac2A+/+ mice, was markedly reduced in Epac2A−/− mice. In contrast, the combinatorial effect of GLP-1 and gliclazide was rather mild, and the effect was not altered by Epac2A ablation. Activation of Rap1 was enhanced by the combination of an Epac-selective cAMP analog with glibenclamide or glimepiride but not gliclazide. In diet-induced obese mice, ablation of Epac2A reduced the insulin secretory response to coadministration of the GLP-1 receptor agonist liraglutide and glimepiride. These findings clarify the critical role of Epac2A/Rap1 signaling in the augmenting effect of incretin and sulfonylurea on insulin secretion and provide the basis for the effects of combination therapies of incretin-related drugs and sulfonylureas.

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Section: Discussionmentioning

confidence: 99%

Role of Epac2A/Rap1 Signaling in Interplay Between Incretin and Sulfonylurea in Insulin Secretion

et al. 2014

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“…The Kanagawa Diabetes Study Group has previously published clinical findings on the short-term efficacy, safety and pleiotropic effects of sitagliptin in large numbers of patients [1][2][3]. The Group has additionally reported long-term maintenance of glycemic control in Japanese patients with type 2 diabetes receiving this drug [4].…”

Section: Introductionmentioning

confidence: 99%

Effects of sitagliptin on the serum creatinine in Japanese type 2 diabetes

Maeda

Kubota

Kanamori

et al. 2015

Diabetes Research and Clinical Practice

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“…Dipeptidyl peptidase-4 DPP4 inhibitors are widely used in Japan, and it is possible to achieve good glycemic control without hypoglycemia using this class of drugs [3][4][5] . However, although patient weight does not usually change when using DPP4 inhibitors, deteriorations in glycemic control may occur with weight gain 6 .…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of luseogliflozin monotherapy in Japanese patients with type 2 diabetes mellitus: a 12-week, randomized, placebo-controlled, phase II study

Seino

Sasaki

Fukatsu

et al. 2014

Current Medical Research and Opinion

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Objective: Luseogliflozin is a novel sodium glucose cotransporter 2 inhibitor for type 2 diabetes mellitus (T2DM) treatment. An exploratory Phase II study was conducted to assess the efficacy and safety of several doses of luseogliflozin in Japanese T2DM patients. Patients and methods:Japanese T2DM patients aged 20-74 years with hemoglobin A1c (HbA1c) of 6.9-10.5%, fasting plasma glucose (FPG) !126 mg/dL and on diet therapy were randomized in a double-blind manner to receive luseogliflozin (0.5, 2.5, or 5 mg) or placebo once daily for 12 weeks (n ¼ 61, 61, 61, and 56, respectively). The primary endpoint was the change in HbA1c from baseline to end of treatment. Other endpoints included FPG, 2 h postprandial plasma glucose (PPG) in a meal tolerance test (MTT), and body weight. Drug safety was also assessed.Trial registration: Japan Pharmaceutical Information Center (identifier: JapicCTI-090908). Results:Changes in HbA1c from baseline to end of treatment were À0.36, À0.62, and À0.75% in the 0.5, 2.5, and 5 mg luseogliflozin groups, respectively, versus þ0.06% in the placebo group (all P50.001). The reductions in FPG and 2 h-PPG in the MTT were also significantly greater in the luseogliflozin groups (all P50.01) without increases in insulin levels from baseline. Luseogliflozin reduced body weight at all doses. There were no significant differences in the incidences of adverse events among groups. Most adverse events were mild in severity. There were no serious adverse events. Conclusions:Although this was a small-scale study with a short duration, all tested doses of luseogliflozin significantly improved glycemic control, reduced body weight, and were well tolerated in Japanese T2DM patients over the 12-week treatment period.

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Efficacy and safety of sitagliptin monotherapy and combination therapy in Japanese type 2 diabetes patients

Cited by 40 publications

References 31 publications

Role of Epac2A/Rap1 Signaling in Interplay Between Incretin and Sulfonylurea in Insulin Secretion

Role of Epac2A/Rap1 Signaling in Interplay Between Incretin and Sulfonylurea in Insulin Secretion

Effects of sitagliptin on the serum creatinine in Japanese type 2 diabetes

Efficacy and safety of luseogliflozin monotherapy in Japanese patients with type 2 diabetes mellitus: a 12-week, randomized, placebo-controlled, phase II study

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