What each regulator records
None of the three documents uses palpitations as a headline side effect; they measure the pulse and the heart tracing instead. The US label reports average heart rate, sinus tachycardia and first-degree atrioventricular (AV) block, a slower passage of the electrical signal between the upper and lower chambers. [1] The EU summary lists sinus tachycardia and first-degree AV block as common, and the EU leaflet translates these as an increased heart rate and slowing of the heart’s electrical currents. [3] Canada counts palpitations directly in its long-term events table and in its list of less common trial reactions, alongside tachycardia. [4]
| Finding and source | Trulicity® | Comparison |
|---|---|---|
| Average heart rate change, US and EU [1][3] | 0.75 mg and 1.5 mg: up 2 to 4 beats per minute | Placebo: not reported |
| Sinus tachycardia reported, US placebo-controlled trials [1] | 0.75 mg: 2.8% · 1.5 mg: 5.6% | Placebo: 3.0% |
| Sinus tachycardia at more than 2 visits [1] | 0.75 mg: 0.4% · 1.5 mg: 1.6% | Placebo: 0.2% |
| Sinus tachycardia with a rise of at least 15 beats per minute [1] | 0.75 mg: 1.3% · 1.5 mg: 2.2% | Placebo: 0.7% |
| Palpitations, Canadian studies of 26 to 104 weeks [4] | 0.75 mg: 19 of 1,671 (1.1%) · 1.5 mg: 8 of 1,671 (0.5%) | All comparators: 13 of 1,844 (0.7%) |
| First-degree AV block [1] | 0.75 mg: 1.7% · 1.5 mg: 2.3% | Placebo: 0.9% |
| EU frequency class [3] | Sinus tachycardia and first-degree AV block: common | — |
Higher doses and a puzzle in the numbers
For the 52-week trial of 1.5 mg, 3 mg and 4.5 mg, the Canadian monograph reports average rises of 1 to 4 beats per minute and fast-rhythm episodes with a jump of more than 15 beats per minute in 4.1%, 4.4% and 4.9% of the three groups. [4] The EU summary describes the same dose trial with sinus tachycardia plus a rise of at least 15 beats per minute in 2.6%, 1.9% and 2.6%. [3] The two documents do not explain why their figures differ, so neither should be read as the final word. A post hoc look at that trial in people at higher cardiovascular risk found heart rate rose by up to 2 beats per minute across doses; a post hoc analysis can describe patterns but was not what the trial was designed to test. [9]
First-degree AV block in the same trial was reported in 1.2%, 3.8% and 1.7%, and Canada notes that the PR change showed no clear dose pattern between 0.75 mg and 4.5 mg. [3][4] On the palpitations row, the higher 1.5 mg dose actually had fewer reports than 0.75 mg, a reminder that small counts move around. [4]
The Canadian cautions
Health Canada’s monograph turns these findings into warnings. A faster heart rate may worsen heart conditions in people with a history of reduced blood flow to the heart muscle (ischaemic heart disease) or fast heart rhythms, and caution is advised. Because a longer PR interval has been linked with a higher risk of new atrial fibrillation, caution also applies to anyone who has had atrial fibrillation, structural heart disease, conduction problems or cardiomyopathy. [4]
The interaction section adds that Trulicity® should be combined carefully with other medicines that raise heart rate, and that its effect alongside other PR-lengthening drugs, such as antiarrhythmics, some calcium channel blockers, beta blockers, digoxin-type medicines, HIV protease inhibitors and somatostatin analogues, has not been studied. [4] None of this means stopping a heart medicine on your own; it means your prescriber and cardiologist should know about both.
What studies of dulaglutide add
A 26-week randomised trial in 755 adults used 24-hour blood pressure monitors to capture day and night readings. Dulaglutide 1.5 mg lowered systolic blood pressure and raised 24-hour heart rate by 2.8 beats per minute compared with placebo; the authors said the mechanism remained unclear. [5] A review of 24-hour monitoring studies placed dulaglutide at about 3 to 4 beats per minute, with rises during both day and night, compared with 6 to 10 for liraglutide and albiglutide. [6]
For rhythm problems, a 2022 meta-analysis of 56 randomised trials found GLP-1 medicines overall did not raise the risk of atrial fibrillation, but a subgroup analysis showed a trend towards more atrial fibrillation with dulaglutide (relative risk 1.40). The authors called for more research, and subgroup findings like this are signals to test rather than settled facts. [7] A single case report describes a 75-year-old woman with known atrial fibrillation whose rhythm became fast and irregular days after her first 0.75 mg dose; she was also vomiting, dehydrated and had acute kidney injury, so several triggers overlapped. [8]
Why the heart may speed up
- Stated in the labels: Trulicity® increases heart rate and lengthens the PR interval on the ECG, without prolonging the QT interval in a dedicated study at 4 mg and 7 mg (section 12.2). [1][4] The labels do not explain the mechanism.
- Proposed but not proven: the review of 24-hour studies suggests a direct effect on the heart’s natural pacemaker, stimulation of the nervous system that speeds the heart, or both, and links larger rises to longer-acting GLP-1 medicines. [6]
- Indirect routes the Trulicity® documents describe: low blood sugar when used with a sulfonylurea or insulin, which lists a fast heartbeat among its signs, and fluid loss from vomiting or diarrhoea. [1][2] MedlinePlus lists a rapid heartbeat among signs of severe dehydration. [12]
Other things that set the heart racing
MedlinePlus lists anxiety, stress or panic, caffeine, nicotine, heavy drinking, exercise, fever, stimulant drugs, diet pills and decongestants such as pseudoephedrine as common triggers. Some palpitations reflect an abnormal rhythm caused by heart or valve disease, abnormal potassium, an overactive thyroid, low oxygen or medicines for asthma, blood pressure or heart conditions. [10] Cleveland Clinic adds pregnancy, anaemia, dehydration, thyroid medicines and heavy or spicy meals. [11]
People using Trulicity® have type 2 diabetes, and MedlinePlus advises contacting a provider promptly about palpitations if you have diabetes or other heart risk factors. [10] Many REWIND participants already had heart disease or several risk factors, which is the group the Canadian cautions have in mind. [1][4]
What helps, according to the sources
For palpitations that a doctor has already checked, MedlinePlus suggests cutting back on caffeine, nicotine and other stimulants, learning ways to reduce stress, trying relaxation, breathing exercises, yoga, meditation or tai chi, exercising regularly and not smoking. It adds that once a serious cause has been ruled out, constantly monitoring your heartbeat can itself add stress, but a sudden change is worth reporting. [10] Cleveland Clinic gives similar advice and suggests asking your provider which exercise programme suits you. [11]
On Trulicity® specifically, Canada asks you to follow your doctor’s advice about the dose and any tests, such as an ECG. [4] If your fast heartbeat comes with shakiness, sweating or hunger and you also take insulin or a sulfonylurea, the US Medication Guide asks you to talk with your provider in advance about how to recognise and handle low blood sugar. [2][13]
Trulicity® is a registered trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Eli Lilly and Company.
When to get help
| Sign | Who to contact | How fast | Source |
|---|---|---|---|
| Palpitations with chest pain, shortness of breath, fainting or near-fainting, unusual sweating or dizziness | Emergency services (911 / 112) | Emergency | MedlinePlus [10] |
| A new irregular or racing heartbeat, or palpitations with tiredness or breathlessness (possible atrial fibrillation or flutter) | Stop Trulicity® and get immediate medical help | Emergency | Canadian patient information [4] |
| Very rapid heartbeat with swelling of the face, lips or throat, trouble breathing or a severe rash | Stop Trulicity® and get emergency help | Emergency | Medication Guide [2] |
| Fast or pounding heartbeat with shakiness, sweating, hunger or confusion, especially if you take insulin or a sulfonylurea | Follow the low blood sugar plan your care team gave you, then tell your prescriber the same day | Today | Medication Guide [2]; MedlinePlus [13] |
| Resting pulse over 100 without exercise, anxiety or fever, or palpitations that are new or have changed | Your doctor, the same day | Today | MedlinePlus [10] |
| Occasional palpitations with no other symptoms | Your prescriber at your next appointment; sooner if they become more frequent | At your next appointment | Cleveland Clinic [11] |
