Active- and placebo-controlled dose-finding study to assess the efficacy, safety, and tolerability of multiple doses of ipragliflozin in patients with type 2 diabetes mellitus

Fonseca, Vivian; Ferrannini, Ele; Wilding, John; Wilpshaar, Wim; Dhanjal, Perminder; Ball, Greg; Klasen, Sally

doi:10.1016/j.jdiacomp.2012.11.005

Cited by 79 publications

(88 citation statements)

References 13 publications

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“…PK properties of ipragliflozin and sitagliptin, pioglitazone or glimepiride were investigated in three separate open-label, randomized, two-way crossover design trials in healthy subjects [31]. These studies demonstrated that acutely, administration of ipragliflozin to sitagliptin, pioglitazone or glimepiride does not change the PK [33] Fonseca et al [40] Wilding et al »31 kg/m 2 , T2DM diagnosis: »5 years) participated in a double-blind, randomized placebo-controlled trial conducted in multiple centers [33]. Subjects received four different once daily doses of ipragliflozin (12.5, 50, 150 or 300 mg), placebo or metformin (1000 increased to 1500 mg/day) for 12 weeks.…”

Section: Pks and Metabolismmentioning

confidence: 99%

“…A number of Phase II and Phase III trials reported similar frequencies of treatment emergent adverse events (TEAE) in the ipragliflozin and placebo groups [30,[33][34][35][36][38][39][40]. Although one Phase III trial [41] demonstrated significantly higher incidence of TEAEs in the ipragliflozin group (76%) compared to placebo (62%), there was no difference in drug-related TEAEs across the groups.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

“…HbA1c reduction combined with a concomitant increase in placebo is 1 --1.3%. The percentage of patients who achieved a target HbA1c of < 7% was significantly higher in the ipragliflozin group compared to the placebo across number of studies [33,34,36,38,39,41]. Ipragliflozin consistently lowered body weight and waist circumference in all reported trials [34,36,38,39,41].…”

Section: Expert Opinionmentioning

confidence: 99%

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Ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes

Hedrington

2015

Expert Opinion on Drug Metabolism & Toxicology

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Section: Pks and Metabolismmentioning

confidence: 99%

Section: Safety and Tolerabilitymentioning

confidence: 99%

Section: Expert Opinionmentioning

confidence: 99%

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Ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes

Hedrington

2015

Expert Opinion on Drug Metabolism & Toxicology

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“…Here, we investigated the effect of ipragliflozin, an orally active and selective SGLT2 inhibitor [20][21][22][23][24], on the simultaneous progression of diabetic retinopathy, nephropathy, and neuropathy in individual SDT fatty rats. …”

Section: Introductionmentioning

confidence: 99%

Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats

Takakura

Toyoshi²,

Hayashizaki

et al. 2016

Life Sciences

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“…19) The GK rats exhibit decreased β-cell numbers and function which is accompanied by mild hyperglycemia, impaired glucose-induced insulin secretion, and peripheral insulin resistance. [20][21][22][23][24] Here, using dual-energy X-ray absorptiometry (DEXA), we investigated the effect of the selective SGLT2 inhibitor ipragliflozin 13,[25][26][27][28][29] on body composition in GK rats.…”

Section: )mentioning

confidence: 99%

The Sodium Glucose Cotransporter 2 Inhibitor Ipragliflozin Promotes Preferential Loss of Fat Mass in Non-obese Diabetic Goto–Kakizaki Rats

Takasu

Hayashizaki

Hirosumi

et al. 2017

Biological & Pharmaceutical Bulletin

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Sodium glucose cotransporter 2 (SGLT2) inhibitors improve hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. In addition to their antihyperglycemic effect, SGLT2 inhibitors also reduce body weight and fat mass in obese and overweight patients with T2DM. However, whether or not SGLT2 inhibitors similarly affect body composition of non-obese patients with T2DM remains unclear. In this study, we investigated the effect of the SGLT2 inhibitor ipragliflozin on body composition in a Goto-Kakizaki (GK) rat model of non-obese T2DM. GK rats were treated with ipragliflozin once daily for 9 weeks, starting at 23 weeks of age. Body composition was then analyzed using dual-energy X-ray absorptiometry. Treatment with ipragliflozin increased urinary glucose excretion, reduced hemoglobin A1c (HbA1c) levels and suppressed body weight gain as the dose increased. Body composition analysis revealed that body fat mass was lower in the ipragliflozin-treated groups than in the control group, while lean body mass and bone mineral contents were comparable between groups. Thus, an SGLT2 inhibitor ipragliflozin was found to promote preferential loss of fat mass in a rat model of non-obese T2DM. Ipragliflozin might also promote preferential loss of fat in non-obese patients with T2DM.Key words ipragliflozin; sodium glucose cotransporter 2 (SGLT2) inhibitor; body composition; anti-diabetic drug; type 2 diabetes mellitus Type 2 diabetes mellitus (T2DM) is characterized by either or both disturbed insulin secretion from pancreatic β-cells or insufficient action of insulin (insulin resistance) in peripheral tissues.1,2) Treatment of T2DM typically starts with diet and exercise to reduce excess body weight, which is effective for glycemic control, 3) as extra fat is known to increase insulin resistance.4) If glycemic control cannot be effectively achieved through diet and exercise, treatment then progresses to the use of several types of oral antihyperglycemic drug. 5,6) However, most of these compounds either induce weight gain (insulin, sulfonylureas, glinides, and thiazolidinediones) or help maintain current weight (metformin, α-glucosidase inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors).5,6) Achieving weight loss along with fat loss using such medications has thus far proven difficult. 7)Sodium glucose cotransporter 2 (SGLT2) inhibitors have recently been developed as antidiabetic drugs. 8,9) SGLT2, a low-affinity and high-capacity glucose transporter, is expressed specifically on the luminal surface of cells in the S1 segment of the proximal tubule 10) and reabsorbs approximately 90% of glucose in the glomerular filtrates in normal glucose-tolerant individuals. 8)SGLT2 inhibitors prevent this reabsorption, thereby increasing urinary glucose excretion and subsequently decreasing blood glucose levels. Treatment with SGLT2 inhibitors improves glycemic parameters and is associated with reduction in body weight in patients with T2DM. 11,12) Further, reduction of waist circumference...

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Active- and placebo-controlled dose-finding study to assess the efficacy, safety, and tolerability of multiple doses of ipragliflozin in patients with type 2 diabetes mellitus

Cited by 79 publications

References 13 publications

Ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes

Ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes

Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats

The Sodium Glucose Cotransporter 2 Inhibitor Ipragliflozin Promotes Preferential Loss of Fat Mass in Non-obese Diabetic Goto–Kakizaki Rats

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