PMID- 25754396
OWN - NLM
STAT- MEDLINE
DCOM- 20160129
LR  - 20221207
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 17
IP  - 6
DP  - 2015 Jun
TI  - Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose 
      co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of 
      metformin.
PG  - 591-598
LID - 10.1111/dom.12460 [doi]
AB  - AIM: To investigate the efficacy and safety of ertugliflozin, in a phase II 
      dose-ranging study, in patients with type 2 diabetes mellitus (T2DM) inadequately 
      controlled on metformin. METHODS: A total of 328 patients [mean T2DM duration, 
      6.3 years; mean glycated haemoglobin (HbA1c), 8.1%] were randomized to once-daily 
      ertugliflozin (1, 5, 10, 25 mg), sitagliptin (100 mg) or placebo, for 12 weeks. 
      The primary efficacy endpoint was change from baseline to week 12 in HbA1c 
      concentration and the secondary efficacy endpoints were changes from baseline to 
      week 12 in body weight, fasting plasma glucose (FPG) and systolic/diastolic blood 
      pressure (SBP/DBP). Safety and tolerability were also monitored. RESULTS: 
      Ertugliflozin (1-25 mg/day) produced significant reductions in HbA1c 
      concentration [placebo-corrected least-squares mean (LSM) -0.45% (1 mg) to -0.72% 
      (25 mg); p </= 0.002, similar to sitagliptin (-0.76%; p = 0.0001)], FPG (LSM -1.17 
      to -1.90 mmol/l; p < 0.0001) and body weight (-1.15 to -2.15%; p < 0.0001). The 
      LSM SBP decreased by -3.4 to -4.0 mmHg from baseline with ertugliflozin 
      5-25 mg/day. No reductions in body weight or blood pressure were observed with 
      sitagliptin. After randomization, 2.7% of patients (9/328) withdrew because of 
      adverse events (AEs); the frequency of AEs was evenly distributed across groups. 
      No dose-related increase in AE frequency occurred with ertugliflozin. 
      Hypoglycaemia was reported in 5 (1.5%) randomized participants (all in the 
      ertugliflozin group). The frequency of urinary tract infection was 3.2% for 
      ertugliflozin (pooled across groups), 1.8% for sitagliptin, 7.4% for placebo, and 
      the frequency of genital fungal infections was 3.7% for ertugliflozin (pooled) 
      versus 1.9% for placebo. CONCLUSION: Ertugliflozin (1-25 mg/day) improved 
      glycaemic control, body weight and blood pressure in patients with T2DM 
      suboptimally controlled on metformin, and was well tolerated.
CI  - (c) 2015 John Wiley & Sons Ltd.
FAU - Amin, N B
AU  - Amin NB
AD  - Pfizer Worldwide Research and Development, Pfizer Inc, Cambridge, MA, USA.
FAU - Wang, X
AU  - Wang X
AD  - Pfizer Worldwide Research and Development, Pfizer Inc, Cambridge, MA, USA.
FAU - Jain, S M
AU  - Jain SM
AD  - TOTALL Diabetes Hormone Institute, Indore, India.
FAU - Lee, D S
AU  - Lee DS
AD  - Pfizer Worldwide Research and Development, Pfizer Inc, Cambridge, MA, USA.
FAU - Nucci, G
AU  - Nucci G
AD  - Pfizer Worldwide Research and Development, Pfizer Inc, Cambridge, MA, USA.
FAU - Rusnak, J M
AU  - Rusnak JM
AD  - Pfizer Worldwide Research and Development, Pfizer Inc, Cambridge, MA, USA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150331
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Blood Glucose)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transport Proteins)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 6C282481IP (ertugliflozin)
RN  - 9100L32L2N (Metformin)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood Glucose/drug effects/metabolism
MH  - Blood Pressure/drug effects
MH  - Body Weight/drug effects
MH  - Bridged Bicyclo Compounds, Heterocyclic/*administration & dosage
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Therapy, Combination/methods
MH  - Female
MH  - Genital Diseases, Female/chemically induced
MH  - Genital Diseases, Male/chemically induced
MH  - Glycated Hemoglobin/drug effects/metabolism
MH  - Humans
MH  - Hypoglycemia/chemically induced
MH  - Hypoglycemic Agents/*administration & dosage
MH  - Male
MH  - Metformin/*administration & dosage
MH  - Middle Aged
MH  - Mycoses/chemically induced
MH  - Sitagliptin Phosphate/administration & dosage
MH  - Sodium-Glucose Transport Proteins/*antagonists & inhibitors
MH  - Urinary Tract Infections/chemically induced
OTO - NOTNLM
OT  - HbA1c
OT  - PF-04971729
OT  - ertugliflozin
OT  - sodium-glucose linked co-transporter (SGLT)
OT  - type 2 diabetes mellitus (T2DM)
EDAT- 2015/03/11 06:00
MHDA- 2016/01/30 06:00
CRDT- 2015/03/11 06:00
PHST- 2014/12/12 00:00 [received]
PHST- 2015/02/21 00:00 [revised]
PHST- 2015/03/03 00:00 [accepted]
PHST- 2015/03/11 06:00 [entrez]
PHST- 2015/03/11 06:00 [pubmed]
PHST- 2016/01/30 06:00 [medline]
AID - 10.1111/dom.12460 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2015 Jun;17(6):591-598. doi: 10.1111/dom.12460. Epub 2015 
      Mar 31.