Document Detail


Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial.
MedLine Citation:
PMID:  22431673     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2, may improve glycemic control with a lower dose of insulin and attenuate the associated weight gain in patients with inadequate control despite high doses of insulin.
OBJECTIVE: To evaluate the efficacy and safety of adding dapagliflozin therapy in patients whose type 2 diabetes mellitus is inadequately controlled with insulin with or without oral antidiabetic drugs.
DESIGN: A 24-week, randomized, placebo-controlled, multicenter trial followed by a 24-week extension period. An additional 56-week extension period is ongoing. (ClinicalTrials.gov registration number: NCT00673231)
SETTING: 126 centers in Europe and North America from 30 April 2008 to 19 November 2009.
PATIENTS: 808 patients with inadequately controlled type 2 diabetes mellitus receiving at least 30 U of insulin daily, with or without up to 2 oral antidiabetic drugs.
INTERVENTION: Patients were randomly assigned in a 1:1:1:1 ratio and allocated with a computer-generated scheme to receive placebo or 2.5, 5, or 10 mg of dapagliflozin, once daily, for 48 weeks.
MEASUREMENTS: The primary outcome was change in hemoglobin A(1c) from baseline to 24 weeks. Secondary outcomes included changes in body weight, insulin dose, and fasting plasma glucose level at 24 weeks and during the 24-week extension period. Adverse events were evaluated throughout both 24-week periods.
RESULTS: 800 patients were analyzed. After 24 weeks, mean hemoglobin A(1c) decreased by 0.79% to 0.96% with dapagliflozin compared with 0.39% with placebo (mean difference, -0.40% [95% CI, -0.54% to -0.25%] in the 2.5-mg group, -0.49% [CI, -0.65% to -0.34%] in the 5-mg group, and -0.57% [CI, -0.72% to -0.42%] in the 10-mg group). Daily insulin dose decreased by 0.63 to 1.95 U with dapagliflozin and increased by 5.65 U with placebo (mean difference, -7.60 U [CI, -10.32 to -4.87 U] in the 2.5-mg group, -6.28 U [CI, -8.99 to -3.58 U] in the 5-mg group, and -6.82 U [CI, -9.56 to -4.09 U] in the 10-mg group). Body weight decreased by 0.92 to 1.61 kg with dapagliflozin and increased by 0.43 kg with placebo (mean differences, -1.35 kg [CI, -1.90 to -0.80 kg] in the 2.5-mg group, -1.42 kg [CI, -1.97 to -0.88 kg] in the 5-mg group, and -2.04 kg [CI, -2.59 to -1.48 kg] in the 10-mg group). These effects were maintained at 48 weeks. Compared with the placebo group, patients in the pooled dapagliflozin groups had a higher rate of hypoglycemic episodes (56.6% vs. 51.8%), events suggesting genital infection (9.0% vs. 2.5%), and events suggesting urinary tract infection (9.7% vs. 5.1%).
LIMITATION: Insulin doses were not titrated to target, and the study was not designed to evaluate long-term safety.
CONCLUSION: Dapagliflozin improves glycemic control, stabilizes insulin dosing, and reduces weight without increasing major hypoglycemic episodes in patients with inadequately controlled type 2 diabetes mellitus.
PRIMARY FUNDING SOURCE: AstraZeneca and Bristol-Myers Squibb.
Authors:
John P H Wilding; Vincent Woo; Norman G Soler; Andrea Pahor; Jennifer Sugg; Katja Rohwedder; Shamik Parikh;
Related Documents :
18413493 - The collecting duct is the major source of prorenin in diabetes.
22669803 - Review of the safety and efficacy of exenatide once weekly for the treatment of type 2 ...
8565423 - Physical activity in the treatment and prevention of diabetes.
Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of internal medicine     Volume:  156     ISSN:  1539-3704     ISO Abbreviation:  Ann. Intern. Med.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-20     Completed Date:  2012-05-02     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  0372351     Medline TA:  Ann Intern Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  405-15     Citation Subset:  AIM; IM    
Affiliation:
University Hospital Aintree, Liverpool, United Kingdom. j.p.h.wilding@liverpool.ac.uk
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00673231
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Blood Glucose / metabolism
Blood Pressure / drug effects
Child
Diabetes Mellitus, Type 2 / blood,  drug therapy*,  physiopathology
Female
Genital Diseases, Female / chemically induced
Genital Diseases, Male / chemically induced
Glucosides / adverse effects,  therapeutic use*
Heart Rate / drug effects
Hemoglobin A, Glycosylated / metabolism
Humans
Hypoglycemia / chemically induced
Hypoglycemic Agents / administration & dosage*
Insulin / administration & dosage*
Male
Middle Aged
Sodium-Glucose Transport Proteins / antagonists & inhibitors*
Treatment Outcome
Weight Loss
Young Adult
Chemical
Reg. No./Substance:
0/2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; 0/Blood Glucose; 0/Glucosides; 0/Hemoglobin A, Glycosylated; 0/Hypoglycemic Agents; 0/Insulin; 0/Sodium-Glucose Transport Proteins
Investigator
Investigator/Affiliation:
F Hoppichler / ; A Luger / ; R Prager / ; M Roden / ; T Kotter / ; G Schernthaner / ; A Borisova / ; I Daskalova / ; K Hristozov / ; G Lazarova / ; M Orbetzova / ; M Petkova / ; A Slavcheva / ; Y Stoykova / ; C Tankova / ; N Veleva / ; S Zaharieva / ; J Ardilouze / ; R Aronson / ; P Boucher / ; J Carthy / ; P Dzongowski / ; D Gaudet / ; S Godsell / ; R Goldenberg / ; R Hart / ; R Houlden / ; S Kaiser / ; H Khandwala / ; D Landry / ; D Lau / ; D O'Keefe / ; J Sigalas / ; G Tellier / ; Y Twum-Barima / ; V Woo / ; J Alanko / ; S Kurl / ; J Mäkelä / ; L Niskanen / ; R Paul / ; M Perhonen / ; S Pihlman / ; A Rissanen / ; J Strand / ; T Valle / ; T Bieler / ; F Fuchs / ; D Götze / ; M Hanefeld / ; A Mölle / ; B Paschen / ; L Rose / ; M Schumacher / ; S Semmler / ; W Sehnert / ; B Tillenburg / ; U Wendisch / ; B Winkelmann / ; S Bain / ; I Farmer / ; G S Jassel / ; D Owen / ; R Reed / ; H Simpson / ; C Strang / ; J Wilding / ; L Deák / ; M Gurzó / ; I Hegyi / ; Z Kerényi / ; A Lászlóczky / ; K Páll / ; J Pénzes / ; I Reiber / ; K Révész / ; A Somogyi / ; G Tamás / ; G Vándorfi / ; M Castro Cabezas / ; E de Koning / ; R Timmerman / ; A van de Wiel / ; C Crisan / ; I Ferariu / ; M Vlaiculescu / ; G Arutyunov / ; A Dreval / ; E Grineva / ; I Karpova / ; Z Kobalava / ; E Krasilnikova / ; V Kukharchuk / ; O Lantseva / ; M Pavlova / ; D Privalov / ; L Strongin / ; S Tereschenko / ; N Vorokhobina / ; T Zhelninova / ; K Belesova / ; J Fabry / ; T Kupcova / ; M Macko / ; V Paulovic / ; L Tomasova / ; J Truban / ; A Vargova / ; A Calle Pascual / ; L De Teresa Parreño / ; S Durán García / ; N Freixenet / ; R Gomis de Barbará / ; O González Albarrán / ; J M González Clemente / ; R Bernstein / ; O Brusco / ; R Graf / ; J Freeman / ; J Hoekstra / ; R Khairi / ; B Lubin / ; P Norwood / ; J Reed / ; J Rosenstock / ; N Soler / ; D Sugimoto / ; T Wahl /
Comments/Corrections
Comment In:
Ann Intern Med. 2012 Mar 20;156(6):466-7   [PMID:  22431678 ]
Summary for patients in:
Ann Intern Med. 2012 Mar 20;156(6):I-44   [PMID:  22431686 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Mutations in the protease gene associated with virological failure to lopinavir/ritonavir-containing...
Next Document:  Peer mentoring and financial incentives to improve glucose control in African American veterans: a r...