PMID- 28086882
OWN - NLM
STAT- MEDLINE
DCOM- 20171004
LR  - 20181113
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 16
IP  - 1
DP  - 2017 Jan 13
TI  - Differential effects of glucagon-like peptide-1 receptor agonists on heart rate.
PG  - 6
LID - 10.1186/s12933-016-0490-6 [doi]
LID - 6
AB  - While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase 
      heart rate (HR), it is insufficiently recognized that the extent varies greatly 
      between the various agonists and is affected by the assessment methods employed. 
      Here we review published data from 24-h time-averaged HR monitoring in healthy 
      individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either 
      short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, 
      exenatide LAR, liraglutide, albiglutide, or dulaglutide (N = 1112; 
      active-treatment arms). HR effects observed in two independent head-to-head 
      trials of lixisenatide and liraglutide (N = 202; active-treatment arms) are also 
      reviewed. Short-acting GLP-1 RAs, exenatide and lixisenatide, are associated with 
      a transient (1-12 h) mean placebo- and baseline-adjusted 24-h HR increase of 
      1-3 beats per minute (bpm). Conversely, long-acting GLP-1 RAs are associated with 
      more pronounced increases in mean 24-h HR; the highest seen with liraglutide and 
      albiglutide at 6-10 bpm compared with dulaglutide and exenatide LAR at 3-4 bpm. 
      For both liraglutide and dulaglutide, HR increases were recorded during both the 
      day and at night. In two head-to-head comparisons, a small, transient mean 
      increase in HR from baseline was observed with lixisenatide; liraglutide induced 
      a substantially greater increase that remained significantly elevated over 24 h. 
      The underlying mechanism for increased HR remains to be elucidated; however, it 
      could be related to a direct effect at the sinus node and/or stimulation of the 
      sympathetic nervous system, with this effect related to the duration of action of 
      the respective GLP-1 RAs. In conclusion, this review indicates that the effects 
      on HR differ within the class of GLP-1 RAs: short-acting GLP-1 RAs are associated 
      with a modest and transient HR increase before returning to baseline levels, 
      while some long-acting GLP-1 RAs are associated with a more pronounced and 
      sustained increase during the day and night. Findings from recently completed 
      trials indicate that a GLP-1 RA-induced increase in HR, regardless of magnitude, 
      does not present an increased cardiovascular risk for subjects with T2DM, 
      although a pronounced increase in HR may be associated with adverse clinical 
      outcomes in those with advanced heart failure.
FAU - Lorenz, Martin
AU  - Lorenz M
AD  - R&D Diabetes Division, Sanofi-Aventis Deutschland GmbH, Industrial Park Hochst, 
      Bldg. H831, 65926, Frankfurt am Main, Germany. martin.lorenz@sanofi.com.
FAU - Lawson, Francesca
AU  - Lawson F
AD  - R&D Diabetes Division, Sanofi, Bridgewater, NJ, USA.
FAU - Owens, David
AU  - Owens D
AD  - Institute of Life Sciences College of Medicine, Swansea University, Swansea, UK.
FAU - Raccah, Denis
AU  - Raccah D
AD  - University Hospital Sainte-Marguerite, Marseille, France.
FAU - Roy-Duval, Christine
AU  - Roy-Duval C
AD  - R&D Diabetes Division, Sanofi, Chilly-Mazarin, France.
FAU - Lehmann, Anne
AU  - Lehmann A
AD  - R&D Clinical Sciences & Operations, Sanofi-Aventis Deutschland GmbH, Frankfurt am 
      Main, Germany.
FAU - Perfetti, Riccardo
AU  - Perfetti R
AD  - Global Medical Affairs, Sanofi, Bridgewater, NJ, USA.
FAU - Blonde, Lawrence
AU  - Blonde L
AD  - Department of Endocrinology, Frank Riddick Diabetes Institute, Ochsner Medical 
      Center, New Orleans, LA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170113
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 62340-29-8 (Glucagon-Like Peptides)
RN  - 839I73S42A (Liraglutide)
RN  - WTT295HSY5 (dulaglutide)
SB  - IM
MH  - Animals
MH  - Cardiovascular Diseases/drug therapy/physiopathology
MH  - Diabetes Mellitus, Type 2/drug therapy/physiopathology
MH  - Glucagon-Like Peptide-1 Receptor/*agonists/*physiology
MH  - Glucagon-Like Peptides/analogs & derivatives/pharmacology/therapeutic use
MH  - Heart Rate/*drug effects/*physiology
MH  - Humans
MH  - Hypoglycemic Agents/pharmacology/therapeutic use
MH  - Immunoglobulin Fc Fragments/pharmacology/therapeutic use
MH  - Liraglutide/pharmacology/therapeutic use
MH  - Recombinant Fusion Proteins/pharmacology/therapeutic use
MH  - Risk Factors
PMC - PMC5237337
OTO - NOTNLM
OT  - Glucagon-like peptide-1 receptor agonist
OT  - Heart rate
OT  - Type 2 diabetes mellitus
EDAT- 2017/01/15 06:00
MHDA- 2017/10/05 06:00
PMCR- 2017/01/13
CRDT- 2017/01/15 06:00
PHST- 2016/09/23 00:00 [received]
PHST- 2016/12/26 00:00 [accepted]
PHST- 2017/01/15 06:00 [entrez]
PHST- 2017/01/15 06:00 [pubmed]
PHST- 2017/10/05 06:00 [medline]
PHST- 2017/01/13 00:00 [pmc-release]
AID - 10.1186/s12933-016-0490-6 [pii]
AID - 490 [pii]
AID - 10.1186/s12933-016-0490-6 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2017 Jan 13;16(1):6. doi: 10.1186/s12933-016-0490-6.