PMID- 30259238
OWN - NLM
STAT- MEDLINE
DCOM- 20191021
LR  - 20191022
IS  - 1534-3170 (Electronic)
IS  - 1523-3782 (Linking)
VI  - 20
IP  - 11
DP  - 2018 Sep 26
TI  - Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Risk Reduction in 
      Type 2 Diabetes Mellitus: Is It a Class Effect?
PG  - 113
LID - 10.1007/s11886-018-1051-2 [doi]
AB  - PURPOSE OF REVIEW: Mimetics and analogs that extend the half-life of native 
      glucagon-like peptide-1 (GLP-1), i.e., glucagon-like peptide-1 receptor agonists 
      (GLP-1 RAs), at therapeutic doses, are indicated as adjuncts to diet and 
      exercise, to improve glycemic control in adults with type 2 diabetes mellitus 
      (T2DM). In patients with T2DM, GLP-1 RAs not only affect improvements in impaired 
      beta cell and alpha cell function, suppress appetite, and induce weight loss but 
      also possess multiple cardiovascular protective properties that potentially have 
      a beneficial impact on atherosclerotic cardiovascular disease (ASCVD) morbidity 
      and mortality. RECENT FINDINGS: Required to demonstrate CV safety, compared to 
      standard-of-care antidiabetic therapies, GLP-1 RAs have revealed statistically 
      significant non-inferiority (p < 0.001), among CV outcome trials (CVOTs) thus far 
      completed. Once-daily liraglutide and once-weekly semaglutide demonstrated 
      significant superiority (p = 0.01 and p = 0.02, respectively), reducing 3-point 
      composite major adverse cardiovascular events (MACE) in extreme risk secondary 
      prevention adults with T2DM. Once-weekly exenatide demonstrated only a 
      non-significant (p = 0.06) favorable trend for CV superiority, possibly due to 
      in-trial mishaps, including placebo drop-ins with other CV protective 
      medications. The short half-life lixisenatide was neutral (p = 0.81) in reducing 
      MACE, most likely due to ineffective once-daily dosing. Structural differences 
      among GLP-1 mimetics and analogs may explain potency differences in both A1C 
      reduction and weight loss that may parallel important cardiovascular protective 
      properties of the GLP-1 RA class. Significant superiority in reducing 3-point 
      composite MACE in adults with T2DM with GLP-1 RAs has been limited to liraglutide 
      and semaglutide. Careful attention to within-trial drop-in of cardioprotective 
      antidiabetic agents assuring equipoise between placebo and investigational 
      product groups might demonstrate significant MACE risk reduction with once-weekly 
      exenatide. Maintenance of 24-h circulating levels, by an alternative 
      administration method, may resurrect lixisenatide as a cardioprotective agent. 
      Before a GLP-1 RA bioequivalence "class effect" claim for composite MACE risk 
      reduction superiority can be fully discussed, we are obliged to wait for the 
      pending results of CVOTs with other GLP-1 RAs, particularly albiglutide and 
      dulaglutide, where steric hindrance may potentially inhibit full mimicry of 
      pharmacologic GLP-1.
FAU - Li, Yixing
AU  - Li Y
AD  - West Anaheim Medical Center, Department of Medicine, OPTI-West, 3033 West Orange 
      Ave, Anaheim, CA, 92804, USA.
FAU - Rosenblit, Paul D
AU  - Rosenblit PD
AD  - Dept. of Medicine, Div. Endocrinology, Diabetes & Metabolism, University 
      California, Irvine, School of Medicine, Irvine, CA, USA. pdrosenblit@yahoo.com.
AD  - Diabetes Out-Patient Clinic, UCI Medical Center, Orange, CA, USA. 
      pdrosenblit@yahoo.com.
AD  - Diabetes / Lipid Management & Research Center, 18821 Delaware St., Suite 202, 
      Huntington Beach, CA, 92648, USA. pdrosenblit@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180926
PL  - United States
TA  - Curr Cardiol Rep
JT  - Current cardiology reports
JID - 100888969
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - Cardiovascular Diseases/*drug therapy
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Drug Administration Schedule
MH  - Glucagon-Like Peptide 1/*analogs & derivatives
MH  - Glucagon-Like Peptide-1 Receptor/*agonists
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage
MH  - Randomized Controlled Trials as Topic
MH  - Risk Factors
MH  - Risk Reduction Behavior
OTO - NOTNLM
OT  - Cardiovascular disease
OT  - ELIXIR
OT  - EXSCEL
OT  - Glucagon-like peptide-1
OT  - HARMONY
OT  - LEADER
OT  - REWIND
OT  - Receptor agonists (GLP-1 RAs)
OT  - SUSTAIN-6
OT  - Type 2 diabetes mellitus (T2DM)
EDAT- 2018/09/28 06:00
MHDA- 2019/10/23 06:00
CRDT- 2018/09/28 06:00
PHST- 2018/09/28 06:00 [entrez]
PHST- 2018/09/28 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
AID - 10.1007/s11886-018-1051-2 [pii]
AID - 10.1007/s11886-018-1051-2 [doi]
PST - epublish
SO  - Curr Cardiol Rep. 2018 Sep 26;20(11):113. doi: 10.1007/s11886-018-1051-2.