Trulicity® (dulaglutide) and diarrhea

The figures, document by document

Two US tables report diarrhea as an adverse reaction: the placebo-controlled pool, where people began on 0.75 mg or 1.5 mg and stayed there, and a 36-week trial in adults on metformin whose dose rose every 4 weeks. ^[1] The Canadian monograph tallies every diarrhea event during treatment, related to the medicine or not, and the EU summary assigns a frequency class. ^[3][4]

A high placebo rate and a plateau above 3 mg

At 6.7%, placebo diarrhea is the highest placebo figure in the US Table 1, so the share that can be put down to Trulicity® is smaller than the headline rates suggest: about two percentage points on 0.75 mg and about six on 1.5 mg. ^[1] Changes in bowel habit were plainly common in these trials even without dulaglutide, and the label does not say why.

In both the US and EU accounts of the higher-dose trial, diarrhea rose sharply from 1.5 mg to 3 mg and then levelled off or dipped slightly at 4.5 mg: 11.4% and 10.7% in the US table, 12.0% and 11.6% in the EU text. ^[1][3] Neither document comments on the plateau. Stopping because of diarrhea in that study was 0.2% on 1.5 mg and 1.0% on each higher dose. ^[3]

What specific trials found

AWARD-7 was an open-label trial of 577 adults with type 2 diabetes and moderate-to-severe chronic kidney disease, all also using mealtime insulin, that compared two dulaglutide doses with insulin glargine for 52 weeks. Diarrhea was reported by 33 of 192 (17%) on 1.5 mg, 30 of 190 (16%) on 0.75 mg and 14 of 194 (7%) on glargine. ^[7] The Canadian monograph adds that 2.6% on 1.5 mg stopped because of diarrhea in that trial, against none on glargine, the highest diarrhea-related stopping rate in the Trulicity® documents. ^[4]

Over a median of 5.4 years in REWIND, diarrhea was reported by 13.6% on dulaglutide 1.5 mg, and 0.7% stopped for it against 0.2% on placebo. ^[4] The post hoc analysis of the higher-dose trial found new cases were most frequent soon after starting 0.75 mg, at no more than 4%, and declined afterwards even as doses rose; several of its authors were affiliated with Eli Lilly. ^[5]

Why the bowel can speed up

• What the label supports: the diarrhea rate rose with dose in the placebo pool, and dulaglutide acts on GLP-1 receptors and slows stomach emptying (section 12.1). ^[1] The label does not explain how this leads to looser stools; the Trulicity® nausea page covers the stomach-emptying effect itself.
• Proposed from trial patterns, not measured as a mechanism: a systematic analysis of 32 GLP-1 trials found diarrhea was dose dependent across the class, and that long-acting agents, the group dulaglutide belongs to, were tied to less nausea and vomiting but more diarrhea than short-acting ones. ^[6] It compared published reports, so it describes a pattern rather than a cause.
• General medical background: MedlinePlus and NIDDK both list medicines among the common causes of diarrhea, which matters when several are started or changed around the same time. ^[8][10]

Other causes to rule out

MedlinePlus names viral stomach flu as the most common cause of diarrhea, followed by food or water contaminated with bacteria or parasites, some antibiotics, magnesium-containing laxatives, and conditions such as coeliac disease, inflammatory bowel disease, irritable bowel syndrome and lactose intolerance; C. difficile infection usually follows a course of antibiotics. ^[8] NIDDK adds magnesium antacids and the sugar alcohols sorbitol, mannitol and xylitol found in some liquid medicines. ^[10]

For many people on Trulicity®, metformin is the first suspect to discuss: MedlinePlus lists diarrhea among its side effects, and everyone in the Trulicity® 3 mg and 4.5 mg trial was taking it. ^[13][1] NIDDK also notes that sugar alcohols in sugar-free gum and sweets can make diarrhea worse, which is worth knowing if you have moved to sugar-free products. ^[12]

Looking after yourself during a bout

NIDDK’s first step is replacing lost fluids and electrolytes with water, broths or other drinks that contain electrolytes. It adds that people with diabetes or kidney disease should check with their doctor before using oral rehydration solutions, because a particular product or amount may suit them better. ^[11] Once your appetite returns you can usually go back to your normal diet; in the meantime it suggests avoiding caffeine, very sugary foods and drinks, sugar alcohols, fatty food and, if it bothers you, milk. ^[12] MedlinePlus suggests small meals through the day instead of three large ones and avoiding fried or greasy food, gassy vegetables, alcohol and fizzy drinks. ^[9]

NIDDK says over-the-counter medicines such as loperamide or bismuth subsalicylate are often suitable for short-lived diarrhea in adults, but not with bloody stools or a fever, and that you should see a doctor if diarrhea gets worse while using them. ^[11] Ask your pharmacist whether either suits you alongside Trulicity® and your other medicines. The US label links fluid loss from diarrhea to reports of acute kidney injury, and asks for kidney checks in people with reduced kidney function who report severe stomach or bowel reactions; the kidney page covers that warning. ^[1] The Medication Guide asks you to keep drinking and to contact your provider promptly if diarrhea does not stop. ^[2]

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