Greater dose-ranging effects on A1C levels than on glucosuria with LX4211, a dual inhibitor of SGLT1 and SGLT2, in patients with type 2 diabetes on metformin monotherapy.

Abstract:

OBJECTIVE:To assess the dose-ranging efficacy and safety of LX4211, a dual inhibitor of sodium-glucose cotransporter (SGLT) 1 and SGLT2, in type 2 diabetes. RESEARCH DESIGN AND METHODS:Type 2 diabetic patients inadequately controlled on metformin were randomly assigned to 75 mg once daily, 200 mg once daily, 200 mg twice daily, or 400 mg once daily of LX4211 or placebo. Primary end point was A1C change from baseline to week 12. Secondary end points included changes in blood pressure (BP) and body weight. RESULTS:Baseline characteristics in 299 patients randomly assigned to LX4211 or placebo in this 12-week dose-ranging study were similar: mean age 55.9 years, A1C 8.1% (65 mmol/mol), BMI 33.1 kg/m(2), and BP 124/79 mmHg. LX4211 significantly reduced A1C to week 12 in a dose-dependent manner by 0.42% (4.6 mmol/mol), 0.52% (5.7 mmol/mol), 0.80% (8.7 mmol/mol), and 0.92% (10.0 mmol/mol), respectively (P < 0.001 each), compared with 0.09% (1.0 mmol/mol) for placebo. Greater A1C reductions were produced by 400 mg once a day than 200 mg once a day LX4211 without higher urinary glucose excretion, suggesting a contribution of SGLT1 inhibition. Significant reductions were seen in body weight (-1.85 kg; P < 0.001) and systolic BP (-5.7 mmHg; P < 0.001), but diastolic BP was unchanged (-1.6; P = 0.164). Adverse events with LX4211 were mild to moderate and similar to placebo, including urinary tract infections and gastrointestinal-related events; genital infections were limited to LX4211 groups (0-5.0%). No hypoglycemia occurred. CONCLUSIONS:Dual inhibition of SGLT1/SGLT2 with LX4211 produced significant dose-ranging improvements in glucose control without dose-increasing glucosuria and was associated with reductions in weight and systolic BP in metformin-treated patients with type 2 diabetes.

journal_name

Diabetes Care

journal_title

Diabetes care

authors

Rosenstock J,Cefalu WT,Lapuerta P,Zambrowicz B,Ogbaa I,Banks P,Sands A

doi

10.2337/dc14-0890

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

431-8

issue

3

eissn

0149-5992

issn

1935-5548

pii

dc14-0890

journal_volume

38

pub_type

杂志文章,多中心研究,随机对照试验
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    pub_type: 杂志文章,随机对照试验

    doi:10.2337/dc15-0515

    authors: Hernandez TL,Van Pelt RE,Anderson MA,Reece MS,Reynolds RM,de la Houssaye BA,Heerwagen M,Donahoo WT,Daniels LJ,Chartier-Logan C,Janssen RC,Friedman JE,Barbour LA

    更新日期:2016-01-01 00:00:00

  • High levels of education are associated with an increased risk of latent autoimmune diabetes in adults: results from the Nord-Trøndelag health study.

    abstract:OBJECTIVE:To investigate whether the risk for autoimmune diabetes in adults differs between socioeconomic groups and to compare such risk with that for type 2 diabetes. RESEARCH DESIGN AND METHODS:The inhabitants of the Norwegian county of Nord-Trøndelag were investigated by questionnaires and clinical examinations on...

    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/dc10-1061

    authors: Olsson L,Ahlbom A,Grill V,Midthjell K,Carlsson S

    更新日期:2011-01-01 00:00:00

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    abstract:OBJECTIVE:To provide reliable data on the incidence of insulin-dependent diabetes mellitus (IDDM) in children (< 15 years of age) in Avellaneda, Argentina. RESEARCH DESIGN AND METHODS:A registry was established in Avellaneda, Argentina. The first registry was started in 1989, retrospective data collection was updated ...

    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/diacare.17.9.1022

    authors: Sereday MS,Martí ML,Damiano MM,Moser ME

    更新日期:1994-09-01 00:00:00

  • Low prevalence of islet autoantibodies in patients with gestational diabetes mellitus.

    abstract:OBJECTIVE:To determine the proportion of patients with gestational diabetes mellitus (GDM) who have serological characteristics typical of IDDM. RESEARCH DESIGN AND METHODS:Islet cell antibodies (ICAs), insulin autoantibodies (IAAs), GAD65, and IA-2 antibodies were measured in 145 pregnant women with GDM, 33 with impa...

    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/diacare.20.1.81

    authors: Dozio N,Beretta A,Belloni C,Castiglioni M,Rosa S,Bosi E,Bonifacio E

    更新日期:1997-01-01 00:00:00

  • Risk of Anemia With Metformin Use in Type 2 Diabetes: A MASTERMIND Study.

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    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/dc20-1104

    authors: Donnelly LA,Dennis JM,Coleman RL,Sattar N,Hattersley AT,Holman RR,Pearson ER

    更新日期:2020-10-01 00:00:00

  • A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes.

    abstract:OBJECTIVE:Supplementation of type II diabetic diets with n-3 fatty acids (FAs) from fish oil (FO) has been associated with lowered triglyceride and VLDL levels, although reports of impaired glycemic control have limited their use. Effects of n-3FAs from nonmarine sources are less well documented. Therefore, an investig...

    journal_title:Diabetes care

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2337/diacare.19.5.463

    authors: McManus RM,Jumpson J,Finegood DT,Clandinin MT,Ryan EA

    更新日期:1996-05-01 00:00:00

  • Blood or urine glucose-based insulin therapy and control of glycemia. Computer-simulation study.

    abstract::Adjustment algorithms for conventional insulin therapy must be tested for safety and efficacy before clinical implementation. We did this by computer simulation. Accordingly, a computer simulator of human intermediary metabolism created 10 randomly chosen diabetic subjects for study. All were well defined with respect...

    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/diacare.13.4.393

    authors: Albisser AM,Sozzi S,Strack TR

    更新日期:1990-04-01 00:00:00

  • Prognostic value of resting heart rate on cardiovascular and renal outcomes in type 2 diabetic patients: a competing risk analysis in a prospective cohort.

    abstract:OBJECTIVE:Epidemiological studies and randomized clinical trials have demonstrated in various populations that resting heart rate (RHR) was an independent predictor of cardiovascular (CV) risk and all-cause mortality. However, few data specifically evaluated the relationship between RHR and long-term CV and renal compl...

    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/dc11-2468

    authors: Miot A,Ragot S,Hammi W,Saulnier PJ,Sosner P,Piguel X,Torremocha F,Marechaud R,Hadjadj S

    更新日期:2012-10-01 00:00:00

  • Insulin analogs--is there a compelling case to use them? No!

    abstract::The availability of insulin analogs has offered insulin replacement strategies that are proposed to more closely mimic normal human physiology. Specifically, there are a considerable number of reports demonstrating that prandial insulin analogs (lispro, aspart, glulisine) have pharmacokinetic and pharmacodynamic profi...

    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/dc13-2915

    authors: Davidson MB

    更新日期:2014-06-01 00:00:00

  • Markers of insulin resistance are strong risk factors for retinopathy incidence in type 1 diabetes.

    abstract:OBJECTIVE:To determine the incidence of retinopathy and the relative importance of its risk factors in type 1 diabetes. RESEARCH DESIGN AND METHODS:This is a 7.3-year follow-up of 764 of 1,215 (63%) people with type 1 diabetes across Europe, aged 15-60 years at baseline with no retinopathy (the EURODIAB Prospective Co...

    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/diacare.24.2.284

    authors: Chaturvedi N,Sjoelie AK,Porta M,Aldington SJ,Fuller JH,Songini M,Kohner EM,EURODIAB Prospective Complications Study.

    更新日期:2001-02-01 00:00:00

  • Assessing the impact of visual acuity on quality of life in individuals with type 2 diabetes using the short form-36.

    abstract:OBJECTIVE:We sought to ascertain quality-of-life measures and utility values associated with visual acuity in type 2 diabetes. RESEARCH DESIGN AND METHODS:The Medical Outcome Study Short Form with 36 items (SF-36) was administered to 4,051 individuals with type 2 diabetes who were enrolled in the Lipids in Diabetes St...

    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/dc05-2150

    authors: Clarke PM,Simon J,Cull CA,Holman RR

    更新日期:2006-07-01 00:00:00

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    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/diacare.18.11.1460

    authors: Lavery LA,Lavery DC,Quebedeax-Farnham TL

    更新日期:1995-11-01 00:00:00

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    journal_title:Diabetes care

    pub_type: 杂志文章,评审

    doi:10.2337/diacare.14.3.249

    authors: Julius S

    更新日期:1991-03-01 00:00:00

  • Personal computer programs to assist with self-monitoring of blood glucose and self-adjustment of insulin dosage.

    abstract::We have developed computer programs in compiled BASIC for the IBM-PC and compatible microcomputers for use by physicians, paramedical personnel, and/or patients to assist with self-monitoring of blood glucose (SMBG) and self-adjustment of insulin dosage. The programs can potentially assist with patient education and m...

    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/diacare.9.1.61

    authors: Pernick NL,Rodbard D

    更新日期:1986-01-01 00:00:00

  • No Evidence of Increase in Calcitonin Concentrations or Development of C-Cell Malignancy in Response to Liraglutide for Up to 5 Years in the LEADER Trial.

    abstract:OBJECTIVE:To describe the changes in serum levels of calcitonin in liraglutide- and placebo-treated patients in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation (LEADER) trial over a 3.5-5-year period. RESEARCH DESIGN AND METHODS:Patients (n = 9,340) wi...

    journal_title:Diabetes care

    pub_type: 杂志文章,随机对照试验

    doi:10.2337/dc17-1956

    authors: Hegedüs L,Sherman SI,Tuttle RM,von Scholten BJ,Rasmussen S,Karsbøl JD,Daniels GH,LEADER Publication Committee on behalf of the LEADER Trial Investigators.

    更新日期:2018-03-01 00:00:00

  • Effects of sucrose on carbohydrate and lipid metabolism in NIDDM patients.

    abstract::Recently, there has been increasing interest toward the liberalization of sucrose in the diets of individuals with non-insulin-dependent diabetes mellitus (NIDDM). However, there is evidence from several well-controlled prospective studies demonstrating that the consumption of moderate amounts of sucrose may result in...

    journal_title:Diabetes care

    pub_type: 杂志文章,评审

    doi:10.2337/diacare.12.1.62

    authors: Hollenbeck CB,Coulston AM,Reaven GM

    更新日期:1989-01-01 00:00:00

  • Impact of diabetes among revascularized patients in Japan and the U.S.

    abstract:OBJECTIVE:Approximately 25% of patients who undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) have diabetes, and the diagnosis of diabetes roughly doubles the mortality risk associated with coronary artery disease. However, the impact of diabetes may differ according to ethnicit...

    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/dc11-1547

    authors: Kohsaka S,Goto M,Nagai T,Lee VV,Elayda M,Furukawa Y,Fukushima M,Komeda M,Sakata R,Ohsugi M,Fukuda K,Wilson JM,Kita T,Kimura T

    更新日期:2012-03-01 00:00:00

  • Motor vehicle accidents and IDDM.

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    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/diacare.11.9.701

    authors: Songer TJ,LaPorte RE,Dorman JS,Orchard TJ,Cruickshanks KJ,Becker DJ,Drash AL

    更新日期:1988-10-01 00:00:00

  • Human leukocyte/endothelial cell interactions and mitochondrial dysfunction in type 2 diabetic patients and their association with silent myocardial ischemia.

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    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/dc12-1224

    authors: Hernandez-Mijares A,Rocha M,Rovira-Llopis S,Bañuls C,Bellod L,de Pablo C,Alvarez A,Roldan-Torres I,Sola-Izquierdo E,Victor VM

    更新日期:2013-06-01 00:00:00

  • Diabetes and impaired fasting glycemia in the tribes of Khagrachari hill tracts of Bangladesh.

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    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/diacare.27.5.1054

    authors: Abu Sayeed M,Mahtab H,Akter Khanam P,Abul Ahsan K,Banu A,Rashid AN,Azad Khan AK

    更新日期:2004-05-01 00:00:00

  • Screening for NIDDM in nonpregnant adults. A review of principles, screening tests, and recommendations.

    abstract::The economic burden of diabetes in the U.S. is now more than 90 billion dollars per year (113-115). In the diabetes community, there is a feeling that aggressive measures to detect diabetes in earlier stages may be warranted. Regardless of whether evidence is convincing that there are benefits from early detection of ...

    journal_title:Diabetes care

    pub_type: 杂志文章,评审

    doi:10.2337/diacare.18.12.1606

    authors: Engelgau MM,Aubert RE,Thompson TJ,Herman WH

    更新日期:1995-12-01 00:00:00

  • Heart rate variability in diabetes: relationship to age and duration of the disease.

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    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/diacare.8.1.64

    authors: Masaoka S,Lev-Ran A,Hill LR,Vakil G,Hon EH

    更新日期:1985-01-01 00:00:00

  • A single nucleotide polymorphism in STK11 influences insulin sensitivity and metformin efficacy in hyperinsulinemic girls with androgen excess.

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    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/dc09-1750

    authors: López-Bermejo A,Díaz M,Morán E,de Zegher F,Ibáñez L

    更新日期:2010-07-01 00:00:00

  • Impaired mitochondrial function and insulin resistance of skeletal muscle in mitochondrial diabetes.

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    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/dc08-2078

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    更新日期:2009-04-01 00:00:00

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    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/dc08-0553

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    更新日期:2008-09-01 00:00:00

  • Predictive properties of impaired glucose tolerance for cardiovascular risk are not explained by the development of overt diabetes during follow-up.

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    journal_title:Diabetes care

    pub_type: 杂志文章

    doi:10.2337/diacare.26.10.2910

    authors: Qiao Q,Jousilahti P,Eriksson J,Tuomilehto J

    更新日期:2003-10-01 00:00:00

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    journal_title:Diabetes care

    pub_type: 杂志文章

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    更新日期:2004-08-01 00:00:00

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    pub_type: 杂志文章

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    更新日期:2020-05-01 00:00:00

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    journal_title:Diabetes care

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

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    pub_type: 杂志文章

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