A Lower Baseline Urinary Glucose Excretion Predicts a Better Response to the Sodium Glucose Cotransporter 2 Inhibitor

We aimed to identify the clinical variables associated with a better glucose-lowering response to the sodium glucose cotransporter 2 inhibitor ipragliflozin in people with type 2 diabetes mellitus (T2DM). We especially focused on urinary glucose excretion (UGE). This was a single-arm multicenter prospective study. A total of 92 people with T2DM aged 20 to 70 years with glycosylated hemoglobin (HbA1c) levels ≥7.0% and ≤9.5% were enrolled. Ipragliflozin (50 mg) was added to the background therapy for these people for 12 weeks. After 3 months treatment with ipragliflozin, the mean HbA1c levels were decreased from 7.6% to 6.9% and 62.0% of the people reached the HbA1c target of less than 7.0% (P<0.001). In addition, body weight, blood pressure, and lipid parameters were improved after ipragliflozin treatment (all P<0.001). The baseline HbA1c (r=0.66, P<0.001) and morning spot urine glucose to creatinine ratio (r=−0.30, P=0.001) were independently associated with the HbA1c reduction. Ipragliflozin treatment for 12 weeks improves glycemic control and other metabolic parameters. A higher HbA1c and lower UGE at baseline predicts a better glucose-lowering efficacy of ipragliflozin.

A Review on Efficacy and Safety of SGLT2 Inhibitors as Add-on Therapy with Metformin

BACKGROUND: The new type of diabetes treatment, SGLT2 inhibitors, has been approved for monotherapy and combination therapy, but medical insurance is only allowed in combination therapy with metformin, which is the first choice for type 2 diabetes treatment. METHODS: The SGLT2 inhibitors prescribed in Korea are dapagliflozin, empagliflozin and ipragliflozin. A review was conducted using Pubmed to evaluate efficacy and safety for these medications with metformin combination therapy. 10 studies were selected by searching for keywords and related references and were reviewed in full. The mechanism of action, pharmacokinetics, and the economics of treatment with SGLT2 inhibitors were examined. RESULTS: SGLT2 inhibitors had moderate glycemic control when added to the treatment of patients with type 2 diabetes who were not being regulated by metformin monotherapy. They also showed positive effects such as weight loss, as well as the lowering of blood pressure. Hypotension and serious side effects were relatively low. However, the risk of genital infection was increased. CONCLUSION: The SGLT2 inhibitors are a new class of drugs that promote glucose excretion in the urine. They are a good choice for combination therapy with metformin for the treatment of type 2 diabetes, with weight loss and very low risk of serious side effects.

Efficacy and Safety of Ipragliflozin in Reducing Body Mass in Patients with Type 2 Diabetes Mellitus:A Systematic Review / 医药导报

Objective To systematically evaluate the efficacy and safety of ipragliflozin in reducing the body weight of patients with type 2 diabetes mellitus. Methods Cochrane Library,PubMed,Embase,Medline,CNKI,CBM,VIP and Wanfang data CBM were screened for randomized controlled trials ( RCTs) of type 2 diabetes mellitus treated with ipragliflozin.After the extraction of the data from RCTs and assessing the methodological quality evaluation,the data were analyzed by RevMan5. 3. 5 software. Results A total of 1688 patients were enrolled in 10 RCTs in the study.Meta-analysis showed that the body mass loss [MD＝-1.56,95%CI＝(-1.88,-1.24),P<0.000 01],mass reduction≥5.0%[RR＝2.17,95%CI＝(1.42,3.32),P＝0.000 3], and waist circumference reduction [MD＝-1.16,95%CI＝(-1.58,-0.74),P<0.000 01) were significantly better than those in the placebo group .The incidence of treatment emergent adverse events [RR＝1.05,95%CI＝(0.97,1.14),P＝0.20] and the incidence of serious adverse events [ RR＝0. 56, 95%CI＝( 0. 29, 1. 05), P＝0. 07] were not significant difference between ipragliflozin and placebo. Conclusion Ipragliflozin can significantly reduce the body mass of patients with type 2 diabetes mellitus,and the adverse reactions are mild. It’s necessary to pay attention to the risk of hypoglycemia when ipragliflzin is combined with insulin.

Drug-induced Liver Injury Caused by Ipragliflozin Administration with Causality Established by a Positive Lymphocyte Transformation Test (LTT) and the Roussel Uclaf Causality Assessment Method (RUCAM): A Case Report

ABSTRACT A 75-year old male patient had been regularly visiting our hospital for the management of his type 2 diabetes mellitus since he was diagnosed at age 64 years. When he developed hypoglycemic episodes with sulfonylurea, ipragliflozin (50 mg/day) was started to replace the sulfonylurea therapy. However, 49 days after starting ipragliflozin, his AST increased from 13 to 622 U/L, ALT increased from 9 to 266 U/L, ALP increased from 239 to 752 U/L, and γ-GTP increased from 19 to 176 U/L. ZTT was 3.5 U, TTT was 0.4 U, and total bilirubin was 0.7 mg/dL. IgM hepatitis A antibody, hepatitis B antigen, hepatitis C virus antibody, IgM CMV antibody, and IgM EB VCA antibody were negative, whereas a lymphocyte transformation test for ipragliflozin was positive. Abdominal CT scan showed mild fatty liver but no sign of nodular lesions. Following admission to our hospital, he received liver supportive therapy with the discontinuation of ipragliflozin therapy. He was discharged from the hospital 18 days later with AST and ALT levels reduced to 20 U/L and 13 U/L, respectively. Based on the clinical presentation of this patient, it is highly important to monitor liver function along with other possible clinical complications (e.g., dehydration, ketosis, and urinary tract infection) associated with SGLT2 inhibitor therapy.

Efficacy and safety of ipragliflozin treatment for type 2 diabetes:a Meta-analysis / 实用医学杂志

Objective To assess the efficacy and safety of ipragliflozin ,a sodium glucose cotransporter 2 (SGLT2)inhibitor,for the treatment of type 2 diabetes. Methods Pubmed,the Cochrane Library,EMbase,CBM and CNKI databases was searched to identify randomized controlled trials(RCTs)pertinent to of ipragliflozin. The risk of bias of the included RCTs was assessed according to the Cochrane Handbook for Systematic Reviews of Inter-ventions Version 5.1.The RevMan 5.3 software was used for Meta-analysis. Results Ten RCTs with 2,390 partici-pants were included,Meta analysis showed that ipragliflozin was more effective than placebo in improving HbA1c level,and could concurrently reduce body weight,blood pressure,and the fasting plasma glucose(FPG)but not increase the risk of hypoglycemia. There were no statistically significant differences in the occurrence of urinary tract infection and genital infection as well as serious adverse events. Conclusion As a safe method ,ipragliflozin can effectively improve the HbA1c level in type 2 diabetes,help patients lose weight and reduce blood pressure.

Ipragliflozin in the treatment of type 2 diabetes:a Meta analysis / 重庆医学

Objective To evaluate the efficacy and safety of different doses of Ipragliflozin in the treatment of type 2 diabetes patients.Methods The randomized controlled trials (RCTs) about Ipragliflozin in treatment of type 2 diabetes patients were retrieved from the databases,including Cochrane Library,PubMed,Embase,Medline,CNKI,Wangfang,VIP and CBM.The data were extracted and evaluated by two researchers independently,and the Meta-analysis was performed via RevMan5.2.Results A total of 10 RCTs involving 1 928 patients were included.The results of Meta-analysis showed that glycosylated hemoglobin (HbA1c)[12.5 mg/d:MD=-0.46,95％CI (-0.69,-0.23);25 mg/d:MD=-0.97,95％CI (-1.00,-0.94);50 mg/d:MD=-0.94,95％CI (-1.20,-0.69);100 mg/d:MD=-0.93,95％CI (-1.72,-0.15);150 mg/d:MD=-0.57,95％CI (-0.89,-0.26);200 mg/d:MD=-0.74,95％CI (-1.14,-0.34);300 mg/d:MD=-0.64,95％CI (-0.86,-0.43)],fasting blood glucose (FPG) [12.5 mg/d:MD=-1.52,95％CI(-1.58,-1.47);25 mg/d:MD=-1.98,95％CI (-2.04,-1.93);50 mg/d:MD=-2.53,95％CI(-2.59,-2.48);100 mg/d:MD=-3.27,95％CI(-3.32,-3.21);150 mg/d:MD=-1.29,95％CI (-1.90,-0.68);200 mg/d:MD=-3.34,95％CI (-4.78,-1.90);300 mg/d:MD=-1.73,95％CI(-2.28,-1.18)] and body weight [12.5mg/d:MD=-0.92,95％CI(-1.36,-0.47);25 mg/d:MD=-1.30,95％CI (-1.81,-0.79);50 mg/d:MD=-1.58,95％CI (-1.80,-1.35);100 mg/d:MD=-1.31,95％CI(-1.65,-0.97);150 mg/d:MD=-1.51,95％CI (-2.42,-0.60);300 mg/d:MD=-1.73,95％ CI (-2.63,-0.83)] were significantly reduced in the different doses of Ipragliflozin group than that in the placebo group,and the dose of 50 mg/d and 100 mg/d were better.There was no significant difference in the incidence rate of the overall adverse reaction,hypoglycemic events,urinary tract infection and genital infection between the different doses of Ipragliflozin group and the placebo group (P＞0.05),but data showed that dose of 50 mg/d was more security than 100 mg/d (RR:1.02 vs.2.18,1.83 vs.2.88,1.01 vs.1.72,1.85 vs.2.98).Conclusion Ipragliflozin is effective and safe for the patients with type 2 diabetes,which could effectively control the patients' HbA1c,FPG and body weight,and 50 mg/d may be the best dose.

Efficacy and safety of ipragliflozin treatment for type 2 diabetes:a Meta-analysis / 实用医学杂志

Objective To assess the efficacy and safety of ipragliflozin ,a sodium glucose cotransporter 2 (SGLT2)inhibitor,for the treatment of type 2 diabetes. Methods Pubmed,the Cochrane Library,EMbase,CBM and CNKI databases was searched to identify randomized controlled trials(RCTs)pertinent to of ipragliflozin. The risk of bias of the included RCTs was assessed according to the Cochrane Handbook for Systematic Reviews of Inter-ventions Version 5.1.The RevMan 5.3 software was used for Meta-analysis. Results Ten RCTs with 2,390 partici-pants were included,Meta analysis showed that ipragliflozin was more effective than placebo in improving HbA1c level,and could concurrently reduce body weight,blood pressure,and the fasting plasma glucose(FPG)but not increase the risk of hypoglycemia. There were no statistically significant differences in the occurrence of urinary tract infection and genital infection as well as serious adverse events. Conclusion As a safe method ,ipragliflozin can effectively improve the HbA1c level in type 2 diabetes,help patients lose weight and reduce blood pressure.

Ipragliflozin in the treatment of type 2 diabetes:a Meta analysis / 重庆医学

Objective To evaluate the efficacy and safety of different doses of Ipragliflozin in the treatment of type 2 diabetes patients.Methods The randomized controlled trials (RCTs) about Ipragliflozin in treatment of type 2 diabetes patients were retrieved from the databases,including Cochrane Library,PubMed,Embase,Medline,CNKI,Wangfang,VIP and CBM.The data were extracted and evaluated by two researchers independently,and the Meta-analysis was performed via RevMan5.2.Results A total of 10 RCTs involving 1 928 patients were included.The results of Meta-analysis showed that glycosylated hemoglobin (HbA1c)[12.5 mg/d:MD=-0.46,95％CI (-0.69,-0.23);25 mg/d:MD=-0.97,95％CI (-1.00,-0.94);50 mg/d:MD=-0.94,95％CI (-1.20,-0.69);100 mg/d:MD=-0.93,95％CI (-1.72,-0.15);150 mg/d:MD=-0.57,95％CI (-0.89,-0.26);200 mg/d:MD=-0.74,95％CI (-1.14,-0.34);300 mg/d:MD=-0.64,95％CI (-0.86,-0.43)],fasting blood glucose (FPG) [12.5 mg/d:MD=-1.52,95％CI(-1.58,-1.47);25 mg/d:MD=-1.98,95％CI (-2.04,-1.93);50 mg/d:MD=-2.53,95％CI(-2.59,-2.48);100 mg/d:MD=-3.27,95％CI(-3.32,-3.21);150 mg/d:MD=-1.29,95％CI (-1.90,-0.68);200 mg/d:MD=-3.34,95％CI (-4.78,-1.90);300 mg/d:MD=-1.73,95％CI(-2.28,-1.18)] and body weight [12.5mg/d:MD=-0.92,95％CI(-1.36,-0.47);25 mg/d:MD=-1.30,95％CI (-1.81,-0.79);50 mg/d:MD=-1.58,95％CI (-1.80,-1.35);100 mg/d:MD=-1.31,95％CI(-1.65,-0.97);150 mg/d:MD=-1.51,95％CI (-2.42,-0.60);300 mg/d:MD=-1.73,95％ CI (-2.63,-0.83)] were significantly reduced in the different doses of Ipragliflozin group than that in the placebo group,and the dose of 50 mg/d and 100 mg/d were better.There was no significant difference in the incidence rate of the overall adverse reaction,hypoglycemic events,urinary tract infection and genital infection between the different doses of Ipragliflozin group and the placebo group (P＞0.05),but data showed that dose of 50 mg/d was more security than 100 mg/d (RR:1.02 vs.2.18,1.83 vs.2.88,1.01 vs.1.72,1.85 vs.2.98).Conclusion Ipragliflozin is effective and safe for the patients with type 2 diabetes,which could effectively control the patients' HbA1c,FPG and body weight,and 50 mg/d may be the best dose.

Addition of Ipragliflozin to Metformin Treatment in Korean Patients with Type 2 Diabetes Mellitus: Subgroup Analysis of a Phase 3 Trial

BACKGROUND: This is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin. METHODS: This multicenter, placebo-controlled, double-blind, parallel-group study was carried out between November 2011 and January 2013. Patients entered a 2-week placebo pretreatment period, followed by a 24-week treatment period with either ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were measured and compared between the two treatment groups for patients enrolled in all 18 study sites in Korea. RESULTS: Eighty-two Korean patients received ipragliflozin (n=43) or placebo (n=39) during the study period. Mean changes in HbA1c levels from baseline to the end of treatment were –0.97% in the ipragliflozin group and –0.31% in the placebo group, with an adjusted between-group difference of –0.60% (P<0.001). Compared to placebo, FPG and body weight also decreased significantly (both P<0.001) from baseline after treatment in the ipragliflozin group, with between-group differences of –21.4 mg/dL and –1.53 kg, respectively. Decreased weight was the most common TEAE in the ipragliflozin group (7.0%); there were no reports of genital and urinary tract infection. CONCLUSION: Ipragliflozin treatment in addition to metformin led to significant improvement in glycemic outcomes and reduction in body weight in Korean patients with type 2 diabetes mellitus, compared with metformin treatment alone; the safety profile was comparable in both groups.