Trulicity® (dulaglutide), heartburn and reflux

Reflux, indigestion and acid across three sets of documents

Dyspepsia is frequent enough to sit in US Table 1, which admits reactions seen in at least 5% of people on Trulicity® and more often than on placebo; reflux disease fell short of that bar and is given in the paragraph underneath. ^[1] A separate 36-week trial compared 1.5 mg, 3 mg and 4.5 mg with a stepwise dose increase and no placebo arm. ^[1] Canada adds hyperchlorhydria and gastritis. Its figures include every event during treatment, not only those judged drug-related, and its longer columns include studies against active treatments as well as placebo. ^[4]

Reading across the rows

In the placebo-controlled pool, reflux disease ran at three to four times the placebo rate and indigestion close to twice, both edging up from 0.75 mg to 1.5 mg. ^[1] The longer Canadian pool is more muted for reflux: once Trulicity® was set against active diabetes treatments for up to two years, the rate on 1.5 mg equalled the comparators. ^[4] Indigestion kept its lead, the acid-excess row was small but higher on both doses than on placebo, and gastritis barely differed from comparators at all. ^[4]

The 36-week dose trial has no placebo column, and indigestion did not climb with dose: 2.8% on 1.5 mg, 5.0% on 3 mg and 2.6% on 4.5 mg. ^[1] Reflux disease is missing from that table because it stayed below 5% in every group. In the REWIND cardiovascular trial, indigestion led 0.2% of people on 1.5 mg to stop treatment, against none on placebo. ^[4]

AWARD-6, a 26-week head-to-head trial in 599 adults on metformin, reported dyspepsia in 8% on dulaglutide 1.5 mg and 6% on liraglutide 1.8 mg, with similar rates of stopping because of adverse events in both groups. ^[7] It was open-label and funded by Eli Lilly and Company. ^[7]

What safety-database studies add

Choi and colleagues compared GLP-1 medicines with DPP-4 inhibitors, another class of diabetes tablets, in three national reporting systems: FAERS in the US, JADER in Japan and Canada Vigilance. Reflux was reported roughly two to five times more often than expected in all three. Dulaglutide’s reporting odds ratios ranged from 2.35 to 3.32, lower than semaglutide’s 3.44 to 6.93, and the signal strengthened with age, reaching 3.01 in people aged 65 and over. ^[5]

An earlier FAERS study by Liu and colleagues, covering 2018 to 2022, found a weaker overall gut signal for dulaglutide (reporting odds ratio 1.39) than for liraglutide or semaglutide. It listed reflux disease and gastritis among reported events it considered absent from the labels it examined, and most gut reports arose within the first month. ^[6] Today the US, EU and Canadian documents all name reflux. ^[1][3][4]

Both are pharmacovigilance studies. They count voluntary reports, which publicity and reporting habits can sway, so they show where reports cluster, not how often reflux happens or whether the medicine caused it.

Why reflux may follow the injection

• Supported by the label: reflux and indigestion occurred more often on Trulicity® than on placebo in controlled trials. ^[1] The label also says dulaglutide delays stomach emptying, a topic our Trulicity® nausea page covers in detail, but it does not name that as the cause of reflux. ^[1]
• Proposed but not measured for dulaglutide: food that stays longer in the stomach could give acid more chances to move upwards. The Gut Liver authors urge closer watch for reflux on these medicines, particularly in older people, without testing a mechanism. ^[5]
• General medical knowledge: reflux happens when the ring of muscle at the lower end of the food pipe, the lower oesophageal sphincter, is weak or relaxes at the wrong moment; overweight, smoking and a hiatal hernia make that more likely. ^[9] Lying down on a full stomach presses contents against that muscle. ^[11]

A full stomach and anaesthesia

Section 5.9 of the US label explains why a slow stomach matters before surgery. There have been rare post-approval reports of pulmonary aspiration, stomach contents entering the lungs, in people on GLP-1 medicines who had general anaesthesia or deep sedation and still had food in the stomach despite following the usual fasting rules. ^[1] The label says the data are too limited to show whether changing fasting instructions or pausing Trulicity® would reduce retained stomach contents, and asks patients to tell their healthcare providers before any planned procedure. ^[1] The Medication Guide puts it simply: let everyone treating you know about Trulicity® before surgery or a procedure. ^[2]

The EU summary asks clinicians to weigh the higher risk of residual stomach content before anaesthesia or deep sedation, and the Canadian monograph says aspiration has been reported with long-acting GLP-1 medicines and should be considered beforehand. ^[3][4] MedlinePlus extends the reminder to dental surgery. ^[12]

A 2025 review in Mayo Clinic Proceedings looked at the endoscopy evidence. GLP-1 medicines were linked to more food left in the stomach at endoscopy, but not to more aspiration. Long-acting forms, dulaglutide among them, higher doses and procedures done during dose increases raised the chance of retained contents. The authors describe shared decision-making about continuing or pausing treatment before a planned endoscopy, say most people can continue, and note that pausing before a colonoscopy may help bowel preparation, although the size of that benefit is still unclear. ^[8] What applies to you is for the team doing the procedure to decide.

Burning that may not come from Trulicity®

NIDDK lists medicines that can cause or worsen reflux, including benzodiazepines, calcium channel blockers for blood pressure, some asthma medicines, NSAID painkillers and tricyclic antidepressants. ^[9] MedlinePlus adds beta-blockers, progestin, theophylline and anticholinergic travel-sickness medicines, and notes that pregnancy can bring heartburn on. ^[11]

MedlinePlus also warns that heartburn is sometimes confused with dyspepsia, and that some people who believe they have heartburn are in fact having a heart attack, which is why burning with chest pressure is an emergency. ^[11] Upper belly pain that spreads to the back is a different matter again; our Trulicity® stomach pain page explains how pancreatitis and gallbladder pain differ.

Relief the guidance describes

MedlinePlus starts with triggers: citrus fruit and juice, peppermint and spearmint, spicy or fatty food, full-fat dairy and tomato products. It then suggests not bending over or exercising straight after eating, finishing meals well before bedtime, avoiding tight belts and waistbands, and stopping smoking. ^[11] NIDDK describes raising the head end of the bed with a foam wedge, losing weight if you are overweight and adjusting eating habits. ^[10] For gut symptoms on these medicines in general, the Mayo Clinic Proceedings review adds smaller, more frequent meals and fewer high-fat foods. ^[8]

Antacids, H2 blockers and proton pump inhibitors are sold over the counter. NIDDK says antacids suit mild symptoms, should not be taken every day or for severe symptoms without a doctor’s advice, and that symptoms persisting despite over-the-counter treatment need a doctor’s review. ^[10] Ask your pharmacist which product fits, and mention Trulicity®: it slows how fast the stomach empties, which the EU leaflet says can affect other medicines. ^[3] MedlinePlus warns against stopping or changing a prescribed medicine you suspect without first talking to your provider. ^[11]

Trulicity® is a registered trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Eli Lilly and Company.