PMID- 25414932
OWN - NLM
STAT- MEDLINE
DCOM- 20150112
LR  - 20221207
IS  - 1941-9260 (Electronic)
IS  - 0032-5481 (Linking)
VI  - 126
IP  - 6
DP  - 2014 Oct
TI  - Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus 
      stratified by cardiovascular disease history and cardiovascular risk factors: 
      analysis of 3 clinical trials.
PG  - 19-32
LID - 10.3810/pgm.2014.10.2818 [doi]
AB  - OBJECTIVE: To test the effectiveness and safety of saxagliptin 5 mg/d in patients 
      with type 2 diabetes mellitus (T2DM) with and without history of cardiovascular 
      disease (CVD) or cardiovascular (CV) risk factors. METHODS: The authors conducted 
      a post hoc analysis of data from 3 randomized studies that compared saxagliptin 
      versus placebo as initial combination therapy with metformin for 24 weeks (N = 
      648) and versus placebo as an add-on to insulin with and without metformin for 24 
      weeks (N = 455), and assessed noninferiority to glipizide as an add-on to 
      metformin for 52 weeks (N = 858). Efficacy outcomes were the adjusted mean change 
      from baseline in glycated hemoglobin (HbA1c) level, fasting plasma glucose 
      concentration, and body weight and the proportion of patients achieving an HbA1c 
      level < 7%. Pairwise comparisons were performed in subgroups with 1) history/no 
      history of CVD, 2) >/= 2 versus 0 to 1 CV risk factors, 3) hypertension/no 
      hypertension, and 4) statin use/no statin use. Adverse events (AE) and 
      hypoglycemia were monitored. RESULTS: In the initial combination therapy study, 
      reductions in HbA1c level from baseline were greater with saxagliptin versus 
      placebo in all subgroups (difference [saxagliptin - placebo], -0.38% to -0.67%). 
      In the add-on to insulin +/- metformin study, differences in adjusted mean change 
      in HbA1c level versus placebo ranged from -0.23% to -0.58% across subgroups. In 
      the noninferiority to glipizide study, adjusted mean changes in HbA1c level were 
      comparable between saxagliptin and glipizide, across subgroups (difference, 
      0.08%-0.21%). No evidence suggested clinically relevant treatment-by-subgroup 
      interactions in pairwise comparison. Incidences of >/= 1 AE were comparable across 
      subgroups. Incidences of confirmed hypoglycemia with saxagliptin were 0 in both 
      metformin add-on studies and 1.2% to 7.8% with saxagliptin + insulin +/- metformin. 
      CONCLUSION: In patients with T2DM, saxagliptin 5 mg/d was similarly effective in 
      improving glycemic control, with an AE profile similar to that of placebo, 
      irrespective of CVD history, number of CV risk factors, hypertension, or statin 
      use. TRIAL REGISTRATION: www.ClinicalTrials.gov identifiers: NCT00327015, 
      NCT00575588, NCT00757588.
FAU - Cook, William
AU  - Cook W
AD  - AstraZeneca, Wilmington, DE. william.cook@astrazeneca.com.
FAU - Minervini, Gianmaria
AU  - Minervini G
FAU - Bryzinski, Brian
AU  - Bryzinski B
FAU - Hirshberg, Boaz
AU  - Hirshberg B
LA  - eng
SI  - ClinicalTrials.gov/NCT00327015
SI  - ClinicalTrials.gov/NCT00575588
SI  - ClinicalTrials.gov/NCT00757588
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Postgrad Med
JT  - Postgraduate medicine
JID - 0401147
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptides)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 9100L32L2N (Metformin)
RN  - 9GB927LAJW (saxagliptin)
RN  - PJY633525U (Adamantane)
RN  - X7WDT95N5C (Glipizide)
SB  - IM
MH  - Adamantane/adverse effects/*analogs & derivatives/therapeutic use
MH  - Adult
MH  - Blood Glucose/metabolism
MH  - Body Weight
MH  - Cardiovascular Diseases/*complications
MH  - Diabetes Mellitus, Type 2/blood/complications/*drug therapy
MH  - Dipeptides/adverse effects/*therapeutic use
MH  - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/*therapeutic use
MH  - Drug Therapy, Combination
MH  - Fasting
MH  - Glipizide/therapeutic use
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Hypoglycemia/chemically induced
MH  - Hypoglycemic Agents/therapeutic use
MH  - Insulin/therapeutic use
MH  - Metformin/therapeutic use
MH  - Risk Factors
EDAT- 2014/11/22 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/11/22 06:00
PHST- 2014/11/22 06:00 [entrez]
PHST- 2014/11/22 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - 10.3810/pgm.2014.10.2818 [doi]
PST - ppublish
SO  - Postgrad Med. 2014 Oct;126(6):19-32. doi: 10.3810/pgm.2014.10.2818.