PMID- 21802144
OWN - NLM
STAT- MEDLINE
DCOM- 20111212
LR  - 20221207
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 33
IP  - 8
DP  - 2011 Aug
TI  - Saxagliptin: a clinical review in the treatment of type 2 diabetes mellitus.
PG  - 1005-22
LID - 10.1016/j.clinthera.2011.06.016 [doi]
AB  - BACKGROUND: Some conventional therapies for type 2 diabetes mellitus (T2DM) fail 
      to address the progressive nature of the disease, and as a result, they may 
      become ineffective in maintaining normoglycemia. Antihyperglycemic agents have 
      been developed to target incretin hormones, specifically glucagon-like peptide 
      (GLP)-1. Incretin analogues and agents that delay GLP-1 degradation, the 
      dipeptidyl peptidase (DPP)-4 inhibitors, offer mechanisms of action that may 
      improve T2DM management. Saxagliptin was approved by the US Food and Drug 
      Administration in July 2009 and by the European Medicines Evaluation Agency in 
      October 2009 for use as monotherapy or in combination regimens for the treatment 
      of T2DM. OBJECTIVE: The aim of this article was to review the mechanism of 
      action, pharmacology, clinical efficacy, and tolerability associated with the use 
      of saxagliptin in patients with T2DM. METHODS: MEDLINE, BIOSIS, International 
      Pharmaceutical Abstracts, and Google Scholar were searched for English-only 
      clinical trials and therapeutic reviews published between 1966 and June 15, 2011 
      (search term: saxagliptin). Additional trials and reviews were identified from 
      the reference lists of published articles. RESULTS: Findings on efficacy and 
      tolerability were obtained from 11 completed Phase III clinical trials. In trials 
      in saxagliptin-naive patients, changes from baseline in glycosylated hemoglobin 
      (HbA(1c)) ranged from -0.72% to -0.90% in the saxagliptin treatment arms compared 
      with -0.27% with placebo (all, P < 0.007). When saxagliptin was used in 
      combination with metformin for 24 weeks, the adjusted mean reductions from 
      baseline in HbA(1c) and the proportions of patients achieving target HbA(1c) 
      (<7.0%) were significantly greater with saxagliptin + metformin compared with 
      monotherapy with either drug (all, P </= 0.0001). When saxagliptin was used in 
      combination with a sulfonylurea or a thiazolidinedione, the changes in HbA(1c) 
      ranged from -0.54% to -0.64% and -0.66% to -0.94%, respectively, in a 
      dose-dependent manner (P </= 0.0007 vs monotherapies). Based on changes in HbA(1c), 
      saxagliptin + metformin was reported to be noninferior to sitagliptin + metformin 
      (-0.52% and -0.62%, respectively; difference, 0.09% [95% CI, -0.01% to 0.20%]). 
      Saxagliptin was reported to have been well tolerated, with the most common 
      adverse events being upper respiratory infection, urinary tract infection, 
      headache, and nasopharyngitis. A systematic review of cardiovascular events in 
      pooled trial results of saxagliptin use reported no increased cardiovascular risk 
      compared with metformin, glyburide, or placebo (relative risk, 0.24 [0.09-0.63]). 
      CONCLUSIONS: Saxagliptin, used as monotherapy and in combination regimens, has 
      been associated with significant reductions in HbA(1c) and significant increases 
      in the rate of achieving target HbA(1c) in patients with T2DM. It has been 
      reported to be well tolerated compared with other oral antihyperglycemic agents. 
      Based on the findings from the studies in this review, the primary role of 
      saxagliptin is expected to be in combination therapy with other antihyperglycemic 
      agents.
CI  - Copyright (c) 2011 Elsevier HS Journals, Inc. All rights reserved.
FAU - Kania, Deanna S
AU  - Kania DS
AD  - Purdue University, College of Pharmacy, Indianapolis, Indiana, USA. 
      deanna.kania@va.gov
FAU - Gonzalvo, Jasmine D
AU  - Gonzalvo JD
FAU - Weber, Zachary A
AU  - Weber ZA
LA  - eng
PT  - Journal Article
PT  - Review
PT  - Systematic Review
DEP - 20110728
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Dipeptides)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 9GB927LAJW (saxagliptin)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/adverse effects/*analogs & derivatives/pharmacology/therapeutic use
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Dipeptides/adverse effects/pharmacology/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects/pharmacology/*therapeutic use
EDAT- 2011/08/02 06:00
MHDA- 2011/12/14 06:00
CRDT- 2011/08/02 06:00
PHST- 2011/06/30 00:00 [accepted]
PHST- 2011/08/02 06:00 [entrez]
PHST- 2011/08/02 06:00 [pubmed]
PHST- 2011/12/14 06:00 [medline]
AID - S0149-2918(11)00485-1 [pii]
AID - 10.1016/j.clinthera.2011.06.016 [doi]
PST - ppublish
SO  - Clin Ther. 2011 Aug;33(8):1005-22. doi: 10.1016/j.clinthera.2011.06.016. Epub 
      2011 Jul 28.