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A randomized, double-blind, placebo-controlled study on long-term efficacy and safety of ipragliflozin treatment in patients with type 2 diabetes mellitus and renal impairment: results of the long-term ASP1941 safety evaluation in patients with type 2 diabetes with renal impairment (LANTERN) study.

ABSTRACT: To assess the effects of renal impairment (RI) on the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus (T2DM).A cohort of Japanese patients with T2DM and mild to moderate RI and poor glycaemic control, despite diet/exercise therapy alone or diet/exercise therapy in combination with an oral hypoglycaemic agent (an ?-glucosidase inhibitor, a sulfonylurea, or pioglitazone), were randomized in a double-blind manner to 50?mg ipragliflozin or placebo once daily for 24?weeks. The patients continued open-label ipragliflozin for a 28-week extension period (total treatment duration: 52?weeks).Ipragliflozin significantly decreased glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels and body weight from baseline to week 24 (last observation carried forward) compared with placebo in all patients with RI. The decreases in HbA1c and FPG levels were statistically significant in patients with mild RI, but not in patients with moderate RI. Ipragliflozin significantly reduced body weight in both RI groups. The improvements in glycaemic control were maintained in the 28-week extension period. Ipragliflozin was associated with no clinically significant safety concerns, and its safety profiles were not influenced by the severity of RI.Ipragliflozin significantly improved glycaemic control and body weight in patients with T2DM with mild RI, but did not improve glycaemic control in patients with moderate RI. Ipragliflozin is a valid treatment option for patients with mild RI but not those with moderate RI.

SUBMITTER: Kashiwagi A

PROVIDER: S-EPMC5024052 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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A randomized, double-blind, placebo-controlled study on long-term efficacy and safety of ipragliflozin treatment in patients with type 2 diabetes mellitus and renal impairment: results of the long-term ASP1941 safety evaluation in patients with type 2 diabetes with renal impairment (LANTERN) study.

Kashiwagi A A Takahashi H H Ishikawa H H Yoshida S S Kazuta K K Utsuno A A Ueyama E E

Diabetes, obesity & metabolism 20150201 2

<h4>Aims</h4>To assess the effects of renal impairment (RI) on the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus (T2DM).<h4>Methods</h4>A cohort of Japanese patients with T2DM and mild to moderate RI and poor glycaemic control, despite diet/exercise therapy alone or diet/exercise therapy in combination with an oral hypoglycaemic agent (an α-glucosidase inhibitor, a sulfonylurea, or pioglitazone), were randomized in a double-blind manner to 50 mg ipragliflozin or ...[more]

PMID: 25347938

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Project description:OBJECTIVE: Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m(2)) are at particular cardiovascular risk. Fenofibrate's safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate's effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. RESEARCH DESIGN AND METHODS: Type 2 diabetic patients (aged 50-75 years) with eGFR ?30 mL/min/1.73 m(2) were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30-59, 60-89, and ?90 mL/min/1.73 m(2)). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine >400 ?mol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat. RESULTS: Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80-0.99]; P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30-59 mL/min/1.73 m(2): 0.68 [0.47-0.97], P = 0.035; eGFR ?90 mL/min/1.73 m(2): 0.85 [0.70-1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment. CONCLUSIONS: Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive.

Project description:IntroductionThe present interim report of the STELLA-LONG TERM study aimed to examine the safety and effectiveness of ipragliflozin in real-word clinical practice in Japan using data up to 12 months. We also evaluated the effect of ipragliflozin on aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in patients with normal vs. abnormal liver function.MethodsThis is an ongoing 3-year post-marketing surveillance study. We analyzed data from Japanese type 2 diabetes mellitus (T2DM) patients who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015 at participating centers in Japan, and whose data were locked by 16 January 2018. The incidence of adverse drug reactions (ADRs) was evaluated for safety. Changes in glycemic control and body weight were evaluated for effectiveness. The effect on liver function was evaluated by changes in the fatty liver index, and changes in AST and ALT were evaluated in patients with normal and abnormal liver function.ResultsThe safety analysis set comprised 11,051 patients and the efficacy analysis set comprised 8788 patients. The incidence rates of ADRs and serious ADRs were 14.6% (1616/11,051) and 0.97% (107/11,051), respectively. Significant reductions (all P < 0.001 vs. baseline, paired t test) in glycated hemoglobin (- 0.8%), fasting plasma glucose (- 31.9 mg/dL), body weight (- 2.9 kg), and fatty liver index (- 8.7) were observed. In patients with normal liver function at baseline, no clinically significant changes in AST and ALT were observed. In patients with abnormal liver function at baseline, clinically and statistically significant decreases (P < 0.05 vs. baseline, two-sample t test) in AST (- 9.0 U/L) and ALT (- 14.7 U/L) levels were observed.ConclusionIpragliflozin was effective and well tolerated in Japanese patients with T2DM over 12 months in the real-world clinical setting. Improvements in liver function parameters (AST and ALT) were observed in T2DM patients with abnormal liver function.Trial registrationClinicalTrials.gov identifier, NCT02479399.FundingAstellas Pharma Inc., Japan.

Project description:INTRODUCTION:International clinical trials have shown that linagliptin significantly improves glycemic control and can be used at a single dose regardless of renal function in patients with type 2 diabetes (T2D). However, to date, no studies have evaluated the use of linagliptin in Japanese patients with T2D by renal function in routine clinical care. METHODS:This was a subgroup analysis of data from a prospective observational post-marketing surveillance (PMS) study of linagliptin conducted in Japan that evaluated the safety and effectiveness of linagliptin in routine clinical care for 3 years in Japanese patients with T2D. The subgroup analysis examined the patient population of this PMS study according to renal function using estimated glomerular filtration rate (eGFR) data. The incidence of linagliptin-related adverse events (adverse drug reactions [ADRs]) was the primary endpoint, and the change in glycated hemoglobin (HbA1c) from baseline to last observation was the secondary endpoint. RESULTS:Of the 2235 patients included in the safety analysis, eGFR was ≥ 90 mL/min/1.73 m2 (defined as group G1) in 16.9% (n = 377), ≥ 60 to < 90 mL/min/1.73 m2 (group G2) in 44.5% (n = 995), ≥ 30 to < 60 mL/min/1.73 m2 (group G3) in 21.7% (n = 486), ≥ 15 to < 30 mL/min/1.73 m2 (group G4) in 2.6% (n = 58) and < 15 mL/min/1.73 m2 (group G5) in 1.7% (n = 37). No eGFR data were available for 12.6% (n = 282) of patients. In these GFR groups, the incidence of ADRs with linagliptin was 6.9% in group G1, 11.1% in group G2, 13.8% in group G3, 15.5% in group G4 and 16.2% in group G5; the change in HbA1c from baseline to the last observation was - 1.11, - 0.64, - 0.35, - 0.46 and - 0.54% in the respective subgroups. CONCLUSIONS:Long-term linagliptin use showed sustained improvements in glycemic control with no new safety concerns regardless of renal function. TRIAL REGISTRATION:ClinicalTrials.gov (NCT01650259). FUNDING:This study was funded by Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly Japan K.K.

Dataset Information

A randomized, double-blind, placebo-controlled study on long-term efficacy and safety of ipragliflozin treatment in patients with type 2 diabetes mellitus and renal impairment: results of the long-term ASP1941 safety evaluation in patients with type 2 diabetes with renal impairment (LANTERN) study.

Publications

A randomized, double-blind, placebo-controlled study on long-term efficacy and safety of ipragliflozin treatment in patients with type 2 diabetes mellitus and renal impairment: results of the long-term ASP1941 safety evaluation in patients with type 2 diabetes with renal impairment (LANTERN) study.

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