Victoza® and stomach pain

Where stomach pain appears in the product information

The three main sources count side effects in different ways, which explains why stomach pain seems to be missing from one and present in the others. The US label pools five placebo-controlled glycemic trials in 1,673 adults treated with Victoza® for an average of 37.3 weeks, and its Table 1 only shows reactions that reached 5% and were more frequent than on placebo. ^[1] Indigestion made it; abdominal pain did not. The European summary of product characteristics sorts reactions into frequency classes, and places upper abdominal pain, abdominal discomfort, gastritis and a swollen abdomen in the common class. ^[2] The Canadian monograph prints each trial separately and lists every event seen in at least 1% of people, whether or not an investigator thought the drug caused it. ^[3]

Timing: the first months and each dose step

The European information says digestive reactions are more frequent at the start of treatment and usually settle within a few days or weeks. ^[2] The US label points the same way from another angle: in its pooled trials, 4.3% of people on Victoza® stopped because of digestive reactions, against 0.5% on placebo, and those withdrawals happened mostly in the first two to three months. ^[1] Severe digestive reactions were reported by 4.4% on 1.2 mg and 4.2% on 1.8 mg, compared with 1.1% on placebo. ^[1]

The label starts adults at 0.6 mg a day for a week before moving to 1.2 mg, with a possible later step to 1.8 mg. ^[1] If more than three days pass without a dose, it says to restart at 0.6 mg to reduce the digestive reactions that can come with restarting. ^[1] Liraglutide has a half-life of about 13 hours and reaches its highest level 8 to 12 hours after an injection, which is why it is given every day. ^[1] So unlike a once-weekly medicine, there is no weekly injection day to line symptoms up against; the useful comparisons are the time of the daily dose, meals and the weeks after a dose step.

When pain is the warning: pancreas and gallbladder

Section 5.2 of the US label asks prescribers to watch for acute pancreatitis after Victoza® is started. Its typical sign is persistent or severe abdominal pain, sometimes running through to the back, which may or may not come with nausea or vomiting. ^[1] In the glycemic control trials there were 13 cases among people on Victoza® and one on a comparator. ^[1] The much larger LEADER trial adjudicated every suspected case: confirmed acute pancreatitis occurred in 18 people on liraglutide (0.4%) and 23 on placebo (0.5%), most more than a year after randomisation. ^[5] Lipase and amylase rose on liraglutide, by 28% and 7% relative to placebo, but those rises did not predict who would develop pancreatitis. ^[5]

The gallbladder story runs the other way. In LEADER, 3.1% on Victoza® and 1.9% on placebo had an acute gallbladder event such as gallstones or inflammation, and most needed hospital care or gallbladder removal. ^[1] A later analysis of the same trial counted 141 of 4,668 people on liraglutide against 88 of 4,672 on placebo (hazard ratio 1.60), with a similar pattern for stones, inflammation and bile duct blockage; the authors note that the trial was not designed for this question and that the mechanism needs further study. ^[6] Canada’s patient information describes an inflamed gallbladder as upper abdominal pain after eating, especially a fatty meal, with nausea, bloating and indigestion. ^[3] Rarely, a blocked bowel can also begin as stomach ache with bloating and vomiting; the EU leaflet calls it a severe form of constipation. ^[2]

Why it happens: what is shown and what is not

What the label supports: part of how liraglutide lowers blood sugar after meals is by slowing how fast the stomach empties. ^[1] Food staying longer in the stomach fits with indigestion, fullness and upper-belly discomfort, and the European table also lists delayed gastric emptying as an uncommon reaction in its own right. ^[2] Constipation, another Victoza® row (5% on either dose against 1% on placebo), can cause cramping pain of its own. ^[1][7]

What is not settled: why gallbladder events rose in LEADER. The authors of the LEADER gallbladder analysis say the mechanism should be studied further, so any single explanation offered online is a hypothesis. ^[6] For pancreatitis the trial picture is mixed: the glycemic control trials counted more cases on Victoza® (13 against 1), while the larger LEADER trial, which had every case checked by a blinded committee, did not (18 against 23). ^[1][5]

Other reasons your stomach can hurt

MedlinePlus groups belly pain by its pattern. Pain across more than half of the abdomen is more typical of a stomach virus, indigestion or gas; pain in one spot points more toward an organ such as the appendix, gallbladder or stomach; cramping is usually gas or bloating; and pain that comes in waves is often caused by kidney stones or gallstones. ^[7] It also stresses that the strength of the pain does not always match how serious the cause is. ^[7]

Common, less serious causes include constipation, irritable bowel syndrome, food intolerance, food poisoning and stomach flu. Others need a clinician: ulcers, reflux, diverticulitis, urinary tract infection, kidney stones, appendicitis and bowel blockage among them. ^[7] For someone with type 2 diabetes, a new pain is worth describing rather than assuming it belongs to the medicine.

What the leaflets and MedlinePlus describe

The Victoza® Medication Guide asks you to drink fluids so that nausea, vomiting or diarrhea do not leave you dehydrated, and to tell your healthcare provider about stomach problems that are severe or do not go away. ^[1] The European leaflet gives the same fluid advice for the start of treatment. ^[2]

For mild belly pain, MedlinePlus describes sipping water or other clear fluids, skipping solid food for a few hours and returning to small amounts of mild food. It reminds people with diabetes to check their blood sugar often while they are unwell. If pain sits high in the abdomen after meals with heartburn, it notes that an antacid may help, and that citrus, fatty or fried food, tomato products, caffeine, alcohol and fizzy drinks are worth avoiding. It also says not to take any medicine for the pain without talking to your provider; a pharmacist can help with that question. ^[7] Smaller, more frequent meals, enough water, fibre and regular activity are listed as ways to prevent some kinds of belly pain. ^[7]

Victoza® is a registered trademark of Novo Nordisk A/S. PepLabo is not affiliated with or endorsed by Novo Nordisk A/S.