18 findings across 12 drug records. Domain pages are descriptive indexes, not advice.
Most represented records
Glucagon (native; Physiology) (4)
Cotadutide (2)
Liraglutide (2)
Retatrutide (2)
Dulaglutide (1)
Evidence spread
High evidence 2Moderate evidence 2Low evidence 9Very low evidence 5
CotadutideMARKETED
heart-rate-chronotropyIncrease
Low evidence
In a single-dose phase 1 study (36 on drug, 12 placebo), the balanced GLP-1/glucagon dual agonist cotadutide (MEDI0382) showed a dose-dependent increase in heart rate;...
SourceAmbery PD et al., Br J Clin Pharmacol 2018;84(10):2325-2335Source
Full findingIn a single-dose phase 1 study (36 on drug, 12 placebo), the balanced GLP-1/glucagon dual agonist cotadutide (MEDI0382) showed a dose-dependent increase in heart rate; treatment-emergent adverse events were mild/moderate (commonest vomiting, nausea, dizziness).
Populationsingle-dose phase 1 study, 36 on drug / 12 placebo
Fundingindustry - AstraZeneca/MedImmune (trial sponsor; inferred from registration trial)
Scope limitssmall sample (N~48); short duration
Comparatorsplacebo
DulaglutideMARKETED
heart-rate-chronotropyIncrease
High evidence
Dulaglutide produces a small increase in pulse rate, consistent with the GLP-1 receptor agonist class, observed in the AWARD-5 dose-finding analysis.
SourceSkrivanek Z, Gaydos BL, Chien JY, et al. Dose-finding results in an adaptive, seamless, r...Source
PopulationAWARD-5: adaptive double-blind randomised dose-finding trial; type 2 diabetes on metformin; pulse rate measured as a Bayesian dose-selection criterion vs placebo at 26 weeks.
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Scope limitsNET-NEW gather (WI-5). Opens the dulaglutide heart-rate-chronotropy cell with a per-drug record (previously inherited only via the SURPASS-CVOT comparator arm). The +0.78 bpm at 2.0 mg with a credible interval crossing zero is recorded faithfully - a small class-consistent chronotropic signal, not a large effect. Observation only; the 'why' open. Industry (Eli Lilly). Council interpretive review not yet run. funding_basis inferred-wrapper at gather; resolve to disclosed locator if load-bearing.
Comparatorsplacebo; sitagliptin
GIP (native; Isoglycaemic Clamp Infusion)MARKETED
heart-rate-chronotropyNo change
Low evidence
Under a two-stage somatostatin (pancreatic) clamp in healthy young men (n=10), native GIP infusion produced NO change in heart rate, blood pressure or flow-mediated...
SourceKarstoft K et al., Am J Physiol Endocrinol Metab 2015;308(5):E426-33Source
Full findingUnder a two-stage somatostatin (pancreatic) clamp in healthy young men (n=10), native GIP infusion produced NO change in heart rate, blood pressure or flow-mediated dilation; the sole haemodynamic change was increased femoral-artery blood flow during hyperglycaemia. The cleanest isolating human GIP haemodynamic dataset - a measured HR null under acute infusion.
A systematic review of native GIP(1-42) administration in humans (67 studies, 30 min to 6 days) found that, among the 15% of studies reporting safety events, the most...
SourceHelsted MM et al., Peptides 2024;177:171214Source
Full findingA systematic review of native GIP(1-42) administration in humans (67 studies, 30 min to 6 days) found that, among the 15% of studies reporting safety events, the most frequent was a moderate and transient increase in heart rate; no correlation between achieved GIP concentration and reported events.
Populationsystematic review of 67 human native-GIP(1-42) administration studies
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsComposite class record; per-agent bpm from secondary/review sources, identifiers not all PubMed-verified this pass. Cross-refs the LIVE HFrEF HR/safety caution.
Comparatorsplacebo
GLP-1 (native; Physiology)MARKETED
heart-rate-chronotropyNot directional
Low evidence
The GLP-1 receptor localises to myocytes of the human (and monkey) sinoatrial node by validated-monoclonal-antibody immunohistochemistry (and to renal/lung arterial...
SourcePyke C et al., Endocrinology 2014;155(4):1280-90Source
Full findingThe GLP-1 receptor localises to myocytes of the human (and monkey) sinoatrial node by validated-monoclonal-antibody immunohistochemistry (and to renal/lung arterial smooth muscle); it is NOT found in working cardiomyocytes - giving an anatomical DIRECT substrate for the GLP-1 heart-rate effect at the sinoatrial node.
Populationhuman and monkey cardiac tissue; validated monoclonal-antibody immunohistochemistry localisation study
Fundingindustry - Novo Nordisk (validated monoclonal antibody; sponsor-authored)
Scope limitssingle-centre/referral-enriched; sponsor-authored COI (Novo Nordisk antibody)
Comparatorsn/a
Glucagon (native; Physiology)MARKETED
heart-rate-chronotropyIncrease
Low evidence
An intravenous glucagon bolus (2 or 5 mg) in 29 patients produced immediate positive inotropy, raised cardiac output and positive chronotropy, peaking within ~10 min...
SourceMurtagh JG et al., Br Heart J 1970;32(3):307Source
Full findingAn intravenous glucagon bolus (2 or 5 mg) in 29 patients produced immediate positive inotropy, raised cardiac output and positive chronotropy, peaking within ~10 min and dissipating within ~30 min; in acute myocardial infarction glucagon raised cardiac output by 42%. The classic human positive-chronotropy/inotropy dataset.
Population29 patients, single intravenous glucagon bolus 2-5 mg
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitssmall sample (N~29); short duration
Comparatorsn/a
Glucagon (native; Physiology)MARKETED
heart-rate-chronotropyIncrease
Very low evidence
Glucagon's positive inotropic/chronotropic cardiac effect is mediated by adenylyl-cyclase activation and inhibition of low-Km cAMP phosphodiesterase, raising cAMP and...
SourceMery PF et al., Nature 1990;345(6271):158-61Source
Full findingGlucagon's positive inotropic/chronotropic cardiac effect is mediated by adenylyl-cyclase activation and inhibition of low-Km cAMP phosphodiesterase, raising cAMP and enhancing the cardiac L-type Ca2+ current (ICa); the effect resembles a beta-adrenergic agent but is NOT blocked by propranolol.
Populationfrog and rat ventricular myocytes
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsanimal data; human relevance uncertain
Comparatorspropranolol
Glucagon (native; Physiology)MARKETED
heart-rate-chronotropyIncrease
Very low evidence
In isolated adult-mouse cardiac preparations, glucagon (0.1-100 nM) exerted concentration-dependent POSITIVE CHRONOTROPY in spontaneously beating right atria -...
SourceNeumann J et al., Int J Mol Sci 2025;27(1):126 (e-pub 2025-12-22)Source
Full findingIn isolated adult-mouse cardiac preparations, glucagon (0.1-100 nM) exerted concentration-dependent POSITIVE CHRONOTROPY in spontaneously beating right atria - reversed by GCGR antagonists and attenuated by the HCN-blocker ivabradine, but not by propranolol or the PDE4 inhibitor rolipram - while DECREASING force of contraction; GCGR mRNA was highest in right atrium.
Populationisolated adult-mouse cardiac preparations (spontaneously beating right atria; ventricle)
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsanimal data; human relevance uncertain
In isolated failing and non-failing human heart tissue (atria, ventricles, sinoatrial nodes), glucagon exerted NO inotropic or chronotropic effect (with or without the...
SourceAranda-Domene R et al. (Hernandez-Cascales), Cardiovasc Diabetol 2023;22(1):128Source
Full findingIn isolated failing and non-failing human heart tissue (atria, ventricles, sinoatrial nodes), glucagon exerted NO inotropic or chronotropic effect (with or without the PDE inhibitor IBMX) and glucagon receptors were NOT detected in the human samples; a non-human positive control confirmed assay validity. The key human-primary contested-null pole.
Populationisolated failing and non-failing human heart tissue (RA/LA/RV/LV/sinoatrial node); positive control confirmed assay validity
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Liraglutide raised sinoatrial firing rate by a DIRECT action on the node in isolated (denervated) rabbit Langendorff hearts and murine SAN myocytes: the effect...
SourceJons C et al., Life Sci 2021;282:119815Source
Full findingLiraglutide raised sinoatrial firing rate by a DIRECT action on the node in isolated (denervated) rabbit Langendorff hearts and murine SAN myocytes: the effect survived beta-blockade (propranolol) but was abolished by funny-current (I_f) blockade with ivabradine, isolating an I_f-mediated direct-SAN component independent of autonomic reflexes.
Populationisolated denervated rabbit Langendorff hearts and isolated murine sinoatrial-node myocytes
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsanimal data; human relevance uncertain
Comparatorspropranolol; ivabradine
RetatrutideINVESTIGATIONAL
heart-rate-chronotropyIncrease
Moderate evidence
Retatrutide caused dose-dependent HR increases peaking at 24 weeks then declining; the largest HR signal observed in the class, with a flagged arrhythmia caution.
SourceJastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526Source
PopulationN=338 adults with obesity; retatrutide 1-12 mg vs placebo; 48 weeks; phase 2 (NCT04881760).
In isolated mouse right atria, retatrutide itself exerted positive chronotropy that was antagonised by the GCGR antagonist adomeglivant, potentiated by rolipram (PDE4...
SourceNeumann J et al., Naunyn Schmiedebergs Arch Pharmacol 2025;398(12):17147-17160Source
Full findingIn isolated mouse right atria, retatrutide itself exerted positive chronotropy that was antagonised by the GCGR antagonist adomeglivant, potentiated by rolipram (PDE4 inhibition) and abolished by the PKA inhibitor H89 - but NOT weakened by propranolol; the authors conclude retatrutide excites beating rate via GCGR, signalling through cAMP/PKA.
Populationisolated mouse right atria (and left atria for force of contraction)
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsanimal data; human relevance uncertain
Semaglutide produces a modest resting heart-rate rise versus placebo (class chronotropic effect).
SourceMarso SP et al. (SUSTAIN-6), NEJM, 2016;375:1834-1844; plus class HR summariesSource
PopulationT2D (SUSTAIN-6) and obesity (STEP) populations; s.c. semaglutide vs placebo.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsconference/abstract-level
Comparatorsplacebo
SurvodutideINVESTIGATIONAL
heart-rate-chronotropyIncrease
Moderate evidence
In the phase 2 obesity dose-finding trial (NCT04667377), survodutide raised heart rate by a mean ~2.7 bpm (all doses pooled) versus ~0.1 bpm on placebo, with a...
Sourcele Roux CW et al., Diabetes Obes Metab 2024;27(2):993-996 (Letter; survodutide BP post hoc)Source
Full findingIn the phase 2 obesity dose-finding trial (NCT04667377), survodutide raised heart rate by a mean ~2.7 bpm (all doses pooled) versus ~0.1 bpm on placebo, with a post-hoc analysis reporting blood-pressure improvement; weight loss up to ~14.9% at 46 weeks.
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