PMID- 24007456
OWN - NLM
STAT- MEDLINE
DCOM- 20140507
LR  - 20221207
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 12
DP  - 2013 Sep 5
TI  - Rationale, design and baseline characteristics of a 4-year (208-week) phase III 
      trial of empagliflozin, an SGLT2 inhibitor, versus glimepiride as add-on to 
      metformin in patients with type 2 diabetes mellitus with insufficient glycemic 
      control.
PG  - 129
LID - 10.1186/1475-2840-12-129 [doi]
AB  - BACKGROUND: Sulfonylureas (SUs) are commonly used in the treatment of type 2 
      diabetes (T2DM), usually as second-line treatment after the failure of metformin. 
      However, SUs are associated with poor durability, hypoglycemia and weight gain. 
      Empagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor in 
      development for the treatment of T2DM. In Phase II/III trials, empagliflozin 
      reduced hyperglycemia, body weight and blood pressure, with a low incidence of 
      hypoglycemia. The aim of this Phase III study is to compare the effects of 
      empagliflozin and the SU glimepiride as second-line therapy in patients with T2DM 
      inadequately controlled with metformin immediate release (IR) and diet/exercise. 
      METHOD: After a 2-week placebo run-in, patients were randomized to receive 
      empagliflozin 25 mg once daily (qd) or glimepiride 1-4 mg qd double-blind for 2 
      years, in addition to metformin IR. Patients who participate in the initial 
      2-year randomization period will be eligible for a 2-year double-blind extension. 
      The primary endpoint is change from baseline in HbA1c. Secondary endpoints are 
      change from baseline in body weight, the incidence of confirmed hypoglycemia and 
      changes in systolic and diastolic blood pressure. Exploratory endpoints include 
      markers of insulin secretion, body composition and responder analyses. Safety 
      endpoints include the incidence of adverse events (AEs) (including macro- and 
      microvascular adverse events) and changes from baseline in clinical laboratory 
      parameters. RESULTS: Between August 2010 and June 2011, 1549 patients were 
      randomized and 1545 patients were treated. At baseline, mean (SD) age was 55.9 
      (10.4) years, HbA1c was 7.92 (0.84)%, body mass index was 30.11 (5.59) kg/m(2), 
      systolic blood pressure was 133.5 (15.9) mmHg and diastolic blood pressure was 
      79.5 (9.4) mmHg. DISCUSSION: This is the largest study to compare the efficacy 
      and safety of an SGLT2 inhibitor with an SU in patients with T2DM inadequately 
      controlled on metformin to date. In addition to determining the effects of these 
      treatments on glycemic control over the long term, this study will investigate 
      effects on beta-cell function, cardiovascular risk factors and markers of renal 
      function/damage. The results will help to inform the choice of second-line 
      treatment in patients with T2DM who have failed on metformin. TRIAL REGISTRATION: 
      Clinicaltrials.gov NCT01167881.
FAU - Ridderstrale, Martin
AU  - Ridderstrale M
AD  - Steno Diabetes Center, Niels Steensens Vej 2-4, DK-2820, Gentofte, Denmark. 
      mtrd@steno.dk.
FAU - Svaerd, Robbyna
AU  - Svaerd R
FAU - Zeller, Cordula
AU  - Zeller C
FAU - Kim, Gabriel
AU  - Kim G
FAU - Woerle, Hans J
AU  - Woerle HJ
FAU - Broedl, Uli C
AU  - Broedl UC
CN  - EMPA-REG H2H-SU trial investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT01167881
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130905
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Biomarkers)
RN  - 0 (Glucosides)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (SLC5A2 protein, human)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0 (Sulfonylurea Compounds)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 6KY687524K (glimepiride)
RN  - 9100L32L2N (Metformin)
RN  - HDC1R2M35U (empagliflozin)
SB  - IM
MH  - Aged
MH  - Benzhydryl Compounds/adverse effects/*therapeutic use
MH  - Biomarkers/blood
MH  - Blood Pressure
MH  - Body Mass Index
MH  - Clinical Protocols
MH  - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy/physiopathology
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Glucosides/adverse effects/*therapeutic use
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects/*therapeutic use
MH  - Male
MH  - Metformin/adverse effects/*therapeutic use
MH  - Middle Aged
MH  - *Research Design
MH  - Sodium-Glucose Transporter 2/metabolism
MH  - *Sodium-Glucose Transporter 2 Inhibitors
MH  - Sulfonylurea Compounds/adverse effects/*therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC3844307
EDAT- 2013/09/07 06:00
MHDA- 2014/05/08 06:00
PMCR- 2013/09/05
CRDT- 2013/09/07 06:00
PHST- 2013/05/28 00:00 [received]
PHST- 2013/08/29 00:00 [accepted]
PHST- 2013/09/07 06:00 [entrez]
PHST- 2013/09/07 06:00 [pubmed]
PHST- 2014/05/08 06:00 [medline]
PHST- 2013/09/05 00:00 [pmc-release]
AID - 1475-2840-12-129 [pii]
AID - 10.1186/1475-2840-12-129 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2013 Sep 5;12:129. doi: 10.1186/1475-2840-12-129.