Trial reportEuropean journal of endocrinology2017

Heart rate acceleration with GLP-1 receptor agonists in type 2 diabetes patients: an acute and 12-week randomised, double-blind, placebo-controlled trial.

Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Trynke Hoekstra, Mark H H Kramer, Michaela Diamant, Daniël H van Raalte

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in European journal of endocrinology, 2017. The graph read 3 numbers from its abstract, feeding 3 cells of the map: it supports the treatment in 1, favours the comparator in 1. Cited by 19 papers, 1 of them a synthesis that pooled it.

3numbers the graph read from it
2cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

← favours the treatmentfavours the comparator →
-12.67.500 · no effect
RHRExenatide-infusion vs placebofavours the comparator · hypertension, t2dfeeds one cell of the map
Δ 7.50<0.001
METHODS: In total, 57 type 2 diabetes patients (mean ± s.d. age: 62.8 ± 6.9 years; BMI: 31.8 ± 4.1 kg/m RESULTS: Exenatide-infusion increased RHR (mean ± s.e.m. +7.5 ± 0.9 BPM, P < 0.001), and systolic and diastolic BP (both P < 0.05), compared with placebo.
Systolic BPliraglutide vs placebofavours the treatment · hypertension, t2dfeeds one cell of the map
Δ -12.6<0.01
Twelve-week treatment with liraglutide increased RHR (+6.6 ± 2.1 BPM), while reducing systolic BP (-12.6 ± 4.7 mmHg) and stroke volume (all P < 0.01).

Read, but not usablea number the graph found but could not read as for or against

RHRliraglutide vs placebodirection of benefit for this outcome is not defined · hypertension, t2dfeeds one cell of the map
Δ 6.60<0.01
Twelve-week treatment with liraglutide increased RHR (+6.6 ± 2.1 BPM), while reducing systolic BP (-12.6 ± 4.7 mmHg) and stroke volume (all P < 0.01).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

GLP-1 receptor agonists×body weight & composition

ContradictsOpen on the map →What to test next →

40 readable studies in this cell: 83 favour the treatment, 15 find no difference, 11 favour the comparator.

Belief with this paper
0.90replicated · 64 families support, 7 contradict · against placebo
Without it
0.91This paper moves it by −0.01.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2017
Δ 7.50
NCT012722193,731 enrolled · 2011
Δ -5.39-5.82 to -4.95
Δ -17.3-18.1 to -16.6
NCT017204463,297 enrolled · 2013
Δ -2.95-3.47 to -2.44
NCT035489351,961 enrolled · 2018
Δ -12.4-13.4 to -11.5
NCT039879191,879 enrolled · 2019
Δ -1.70-2.60 to -0.70
NCT026078651,864 enrolled · 2016
Δ -2.50-3.00 to -2.00
NCT056467061,407 enrolled · 2023
Δ -14.8-16.2 to -13.4
NCT018365231,398 enrolled · 2013
Δ -4.90-5.65 to -4.16
NCT035527571,210 enrolled · 2018
Δ -6.21-7.28 to -5.15
NCT007344741,202 enrolled · 2008
Δ -1.50-2.08 to -0.92
Δ -10.4-11.2 to -9.50
NCT020581471,170 enrolled · 2014
Δ 14.38.37 to 20.3

GLP-1 receptor agonists×blood pressure

SupportsOpen on the map →What to test next →

10 readable studies in this cell: 4 favour the treatment, 5 find no difference, 1 favour the comparator.

Belief with this paper
0.50contested · 3 families support, 1 contradict · against placebo
Without it
0.39This paper moves it by +0.11.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2017
Δ -12.6
NCT00676338820 enrolled · 2008
Δ 0.36-1.02 to 1.73
NCT00781937422 enrolled · 2008
Treatment Contrast -2.72-4.69 to -0.76
NCT02492763176 enrolled · 2015
Δ -1.10-6.20 to 4.10
change -0.90-1.60 to -0.10
NCT04019197108 enrolled · 2019
β coefficient -0.05-0.10 to -0.01
NCT0488111060 enrolled · 2021
Δ -0.00-5.80 to 5.80

GLP-1 receptor agonists×cardiac & vascular function

No readable resultOpen on the map →What to test next →

6 readable studies in this cell: 3 favour the treatment, 2 find no difference, 1 favour the comparator.

Belief with this paper
0.50contested · 3 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
change 0.670.55 to 0.80
NCT04788511529 enrolled · 2021
Δ 7.804.80 to 10.9
NCT0488111060 enrolled · 2021
Δ 25.121.8 to 28.3

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

  1. Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus and Cardiovascular Disease: The Past, Present, and Future.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2022
    Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Review
  6. GLP-1 Receptor Agonist Prescription Patterns in themedRxiv : the preprint server for health sciences · 2026
    Article
  7. Article
  8. Possible mechanisms of action of glucagon-like peptide-1 receptor agonists on blood pressure beyond body weight.Hypertension research : official journal of the Japanese Society of Hypertension · 2025
    Review
  9. Article
  10. Observational
  11. Review
  12. Article
  13. Review
  14. Safety of Semaglutide.Frontiers in endocrinology · 2021 · on this map
    Review
  15. Review
  16. Review
  17. Observational
  18. Article
  19. Article
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Mark M SmitsDepartment of Internal MedicineDiabetes Center, VU University Medical Center, Amsterdam, The Netherlands mm.smits1@vumc.nl.
Lennart TonneijckDepartment of Internal MedicineDiabetes Center, VU University Medical Center, Amsterdam, The Netherlands.
Marcel H A MuskietDepartment of Internal MedicineDiabetes Center, VU University Medical Center, Amsterdam, The Netherlands.
Trynke HoekstraDepartment of Health Sciences and the EMGO Institute for Health and Care ResearchVU University, Amsterdam, The Netherlands and Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
Mark H H KramerDepartment of Internal MedicineDiabetes Center, VU University Medical Center, Amsterdam, The Netherlands.
Michaela DiamantDepartment of Internal MedicineDiabetes Center, VU University Medical Center, Amsterdam, The Netherlands.
Daniël H van RaalteDepartment of Internal MedicineDiabetes Center, VU University Medical Center, Amsterdam, The Netherlands.
Amsterdam UMC Location VUmc · NL

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

objectiveTo examine mechanisms underlying resting heart rate (RHR) increments of GLP-1 receptor agonists in type 2 diabetes patients.

designAcute and 12-week randomised, placebo-controlled, double-blind, single-centre, parallel-group trial.

methodsIn total, 57 type 2 diabetes patients (mean ± s.d. age: 62.8 ± 6.9 years; BMI: 31.8 ± 4.1 kg/m

resultsExenatide-infusion increased RHR (mean ± s.e.m. +7.5 ± 0.9 BPM, P < 0.001), and systolic and diastolic BP (both P < 0.05), compared with placebo. Vascular resistance increased during exenatide-infusion, whereas stroke volume and arterial stiffness decreased (P < 0.05). SNS activity and cardiac output were unaffected. Twelve-week treatment with liraglutide increased RHR (+6.6 ± 2.1 BPM), while reducing systolic BP (-12.6 ± 4.7 mmHg) and stroke volume (all P < 0.01). Cardiac output, vascular resistance, arterial stiffness and SNS activity remained unchanged (all P > 0.05).

conclusionsRHR acceleration with acute and 12-week GLP-1 receptor agonist treatment in type 2 diabetes patients is not explained by changes in SNS activity, and our data argue against vasodilation. In line with pre-clinical data, direct sino-atrial stimulation may be involved.

Indexed as

AgedBlood GlucoseBlood PressureDiabetes Mellitus, Type 2Double-Blind MethodExenatideFemaleGlucagon-Like Peptide-1 ReceptorHeart RateHumansHypoglycemic AgentsLiraglutideMaleMetforminMiddle AgedPeptidesBlood GlucoseExenatideGlucagon-Like Peptide-1 ReceptorHypoglycemic AgentsLiraglutideMetforminPeptidesSulfonylurea CompoundsVenoms

Identifiers

PMID27777261
OpenAlexW2536045672

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.