Efficacy and Safety of Ipragliflozin in Japanese Patients With Type 2 Diabetes: Interim Outcome of the ASSIGN-K Study

Iizuka, Takashi; Iemitsu, Kotaro; Takihata, Masahiro; Takai, Masahiko; Nakajima, Shigeru; Minami, Nobuaki; Umezawa, Shinichi; Kanamori, Akira; Takeda, Hiroshi; Kawata, Takehiro; Ito, Shogo; Kikuchi, Taisuke; Amemiya, Hikaru; Kaneshiro, Mizuki; Mokubo, Atsuko; Takuma, Tetsuo; Machimura, Hideo; Tanaka, Keiji; Asakura, Taro; Kubota, Akira; Aoyagi, Sachio; Hoshino, Kazuhiko; Ishikawa, Masashi; Matsuzawa, Yoko; Obana, Mitsuo; Sasai, Nobuo; Kaneshige, Hideaki; Minagawa, Fuyuki; Saito, Tatsuya; Shinoda, Kazuaki; Miyakawa, Masaaki; Tanaka, Yasushi; Terauchi, Yasuo; Matsuba, Ikuro

doi:10.14740/jocmr2417w

Cited by 38 publications

(59 citation statements)

References 24 publications

(30 reference statements)

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“…The efficacy and safety of SGLT2 inhibitors, either as monotherapy or in combination with other drugs, in Japanese patients with T2DM has been reported in several studies . Because a large proportion of patients with T2DM in Japan are taking a DPP‐4 inhibitor, SGLT2 inhibitors are often prescribed as add‐on therapy to DPP‐4 inhibitors in clinical practice . SGLT2 inhibitors block glucose reabsorption in the kidney, and their use in combination with a DPP‐4 inhibitor brings together distinct mechanisms of action for reducing glucose levels .…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of canagliflozin as add‐on therapy to teneligliptin in Japanese patients with type 2 diabetes mellitus: Results of a 24‐week, randomized, double‐blind, placebo‐controlled trial

Kadowaki

Inagaki

Kondo³

et al. 2017

Diabetes Obesity Metabolism

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AimsTo investigate efficacy and safety of the sodium–glucose co‐transporter 2 (SGLT2) inhibitor canagliflozin administered as add‐on therapy to the dipeptidyl peptidase‐4 (DPP‐4) inhibitor teneligliptin in patients with type 2 diabetes mellitus (T2DM).Materials and methodsWe conducted a multicentre, randomized, double‐blind, placebo‐controlled, phase 3 clinical trial in Japanese patients with T2DM who had inadequate glycaemic control with teneligliptin. Patients were randomized to receive teneligliptin 20 mg plus either canagliflozin 100 mg (T + C, n = 70) or placebo (T + P, n = 68) once daily. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24. Other endpoints included changes in fasting plasma glucose, body weight, proinsulin/C‐peptide ratio, homeostatic model assessment 2‐%B and adverse events. Patients also underwent mixed‐meal tolerance tests.ResultsThe difference between the T + C and T + P groups for HbA1c change from baseline to week 24 was −0.88% (least‐squares mean, P < .001). Fasting plasma glucose, body weight and the proinsulin/C‐peptide ratio were significantly lower in the T + C group than in the T + P group. Homeostatic model assessment 2‐%B improved with T + C compared with T + P. The T + C group exhibited a decrease in the 2‐hour postprandial plasma glucose and plasma glucose area under the curve (AUC)0‐2h in a mixed‐meal tolerance test. No significant between‐group differences were observed for C‐peptide AUC0 ‐2h or glucagon AUC0 ‐2h after meals. Incidences of adverse events were 60.0% and 47.1% in the T + C and T + P groups, respectively. No hypoglycaemia was observed.ConclusionsCanagliflozin administered as add‐on therapy to teneligliptin was effective and well tolerated in Japanese T2DM patients.

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Section: Introductionmentioning

confidence: 99%

Efficacy and safety of canagliflozin as add‐on therapy to teneligliptin in Japanese patients with type 2 diabetes mellitus: Results of a 24‐week, randomized, double‐blind, placebo‐controlled trial

Kadowaki

Inagaki

Kondo³

et al. 2017

Diabetes Obesity Metabolism

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Section: )mentioning

confidence: 99%

“…In a clinical study of overweight patients with T2DM, treatment with ipragliflozin induced modest weight loss accompanied by a reduction in fat mass, while also improving glycemic control. 14,15) Analysis of body composition revealed that the reduction of body fat was the largest contributor to the reduction in body weight. 15) Dapagliflozin also reduced total body weight in obese patients with T2DM, predominantly by reducing total-body fat mass, wherein the decrease in visceral fat mass was greater than that in subcutaneous fat mass.…”

Section: )mentioning

confidence: 99%

“…14,15) Analysis of body composition revealed that the reduction of body fat was the largest contributor to the reduction in body weight. 15) Dapagliflozin also reduced total body weight in obese patients with T2DM, predominantly by reducing total-body fat mass, wherein the decrease in visceral fat mass was greater than that in subcutaneous fat mass. 38,39) Merovci et al further demonstrated that two weeks' treatment with dapagliflozin improved muscle insulin sensitivity in obese patients with T2DM.…”

Section: )mentioning

confidence: 99%

“…11,12) Further, reduction of waist circumference or fat mass has been reported in overweight or obese patients with T2DM. [13][14][15] In animal studies, SGLT2 inhibitors enhanced glucosuria, increased usage of fatty acids instead of glucose as an energy source, and reduced body fat mass in high-fat diet-induced obese (DIO) rats.16-18) However, whether or not SGLT2 inhibitors similarly affect body weight and body composition in non-obese T2DM patients or animal models of T2DM remains unclear.Goto-Kakizaki (GK) rats, a model of spontaneous nonobese T2DM, were produced from a colony of non-diabetic Wistar rats by selective breeding with glucose intolerance as a selection index.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.…”

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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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Adverse Drug Events Observed with the Novel Sodium/Glucose Co-Transporter 2 Inhibitor Ipragliflozin for the Treatment of Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Studies

et al. 2020

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Introduction: Type 2 diabetes mellitus (T2DM) is becoming a major issue worldwide. To effectively control the blood sugar of patients with T2DM, several novel oral hypoglycemic agents (OHAs) are being developed. Sodium/glucose co-transporter 2 (SGLT 2) inhibitors have recently shown beneficial outcomes in patients with T2DM. In this analysis, we aimed to systematically compare the adverse drug events observed with ipragliflozin versus placebo for the treatment of patients with T2DM. Methods: http://www.ClinicalTrials.gov, the bibliographic database of life science and

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Efficacy and Safety of Ipragliflozin in Japanese Patients With Type 2 Diabetes: Interim Outcome of the ASSIGN-K Study

Cited by 38 publications

References 24 publications

Efficacy and safety of canagliflozin as add‐on therapy to teneligliptin in Japanese patients with type 2 diabetes mellitus: Results of a 24‐week, randomized, double‐blind, placebo‐controlled trial

Efficacy and safety of canagliflozin as add‐on therapy to teneligliptin in Japanese patients with type 2 diabetes mellitus: Results of a 24‐week, randomized, double‐blind, placebo‐controlled trial

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

Adverse Drug Events Observed with the Novel Sodium/Glucose Co-Transporter 2 Inhibitor Ipragliflozin for the Treatment of Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Studies

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