Short answer: The Xultophy label names low blood sugar as the most common side effect of insulin-containing products. Across trials of 1,881 people with type 2 diabetes, the other most common reactions were nasopharyngitis (10%), headache (9%), nausea (8%), diarrhea (8%), increased lipase (7%) and upper respiratory tract infection (6%). The table has no placebo column. Xultophy has a boxed warning about thyroid C-cell tumors.
What Xultophy is approved for: Xultophy 100/3.6 is approved, along with diet and exercise, to improve blood sugar control in adults with type 2 diabetes (section 1). The label says it is not recommended with any other product containing liraglutide or another GLP-1 receptor agonist, is not for diabetic ketoacidosis, and has not been studied with mealtime (prandial) insulin.
Source
XULTOPHY 100/3.6 (insulin degludec and liraglutide) injection, for subcutaneous use, prescribing information and Medication Guide. Novo Nordisk. DailyMed, version published November 17, 2025. DailyMed setid 21335fe4-d395-4501-ac2a-2f20d7520da9
WARNING: RISK OF THYROID C-CELL TUMORS
Liraglutide, one of the two medicines in Xultophy, causes thyroid C-cell tumors in rats and mice, depending on dose and length of treatment, at exposures relevant to people. It is unknown whether Xultophy causes these tumors, including medullary thyroid carcinoma (MTC), in humans. Xultophy must not be used by anyone with a personal or family history of MTC or with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Symptoms of thyroid tumors include a neck mass, trouble swallowing, shortness of breath or lasting hoarseness. Routine calcitonin blood tests or thyroid ultrasound are of uncertain value for finding MTC early.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Xultophy.
| Adverse reaction | XULTOPHY 100/3.6 N = 1881 % |
|---|---|
| Nasopharyngitis | 10 |
| Headache | 9 |
| Nausea | 8 |
| Diarrhea | 8 |
| Increased Lipase | 7 |
| Upper respiratory tract infection | 6 |
Six trials with 1,881 people with type 2 diabetes on Xultophy for a mean of 33 weeks; mean age 57, mean diabetes duration 9 years. The table has no placebo column.
| Trial (prior treatment) | Total Subjects (N) | Severe Hypoglycemia (%) | Hypoglycemia with a glucose level <54 mg/dL (%) |
|---|---|---|---|
| NCT01336023 (naïve to basal insulin or GLP-1 receptor agonist) | 825 | 0.2 | 27.6 |
| NCT01618162 (naïve to basal insulin or GLP-1 receptor agonist) | 288 | 0.7 | 37.2 |
| NCT02773368 (naïve to basal insulin or GLP-1 receptor agonist) | 209 | 0.5 | 14.4 |
| NCT01676116 (currently on GLP-1 receptor agonist) | 291 | 0.3 | 27.1 |
| NCT01392573 (currently on basal insulin) | 199 | 0.5 | 22.1 |
| NCT01952145 (currently on basal insulin) | 278 | 0 | 24.8 |
Severe hypoglycemia means an episode needing another person to give carbohydrate, glucagon or other help. The under-54 mg/dL row counts episodes with or without symptoms. The label says no clinically important difference in severe low blood sugar was seen between Xultophy and comparators.
Severe stomach and gut reactions in one trial: 0.8% on Xultophy vs 2.9% on liraglutide alone and 0.2% on insulin degludec alone. Stomach and gut reactions may be more frequent at the start and ease within a few days or weeks.
Injection-site reactions were reported in 2.6% of people on Xultophy, usually mild and passing.
Heart rate rose by an average of 2 to 3 beats per minute from baseline, which the label attributes to liraglutide.
Weight gain can occur with insulin products. In Study A, people switching from liraglutide to Xultophy gained an average of 2 kg after 26 weeks.
Calcitonin rose above 20 ng/L in 0.7% on Xultophy and 0.7% on placebo (from under 20 ng/L at baseline); the label says the meaning is unknown.
In liraglutide glycemic trials: papillary thyroid cancer 7 cases vs 1 on comparator (1.5 vs 0.5 per 1,000 patient-years); pancreatitis 13 cases vs 1 (2.7 vs 0.5 per 1,000 patient-years). In the LEADER heart outcomes trial, gallstones were 1.5% vs 1.1% on placebo and acute gallbladder inflammation 1.1% vs 0.7%.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Risk of thyroid C-cell tumors. The boxed warning risk. Xultophy is not for people with a personal or family history of MTC or with MEN 2. Cases of MTC have been reported after approval in people on liraglutide; the label says these reports cannot establish or rule out a cause.
Acute pancreatitis. Pancreatitis, including fatal forms, has been seen with GLP-1 receptor agonists including liraglutide. Signs include lasting or severe stomach pain, sometimes spreading to the back. If it is suspected, Xultophy is stopped.
Never share a pen. A Xultophy pen must never be shared, even with a new needle, because of the risk of passing on blood-borne infections.
Changes in insulin regimen. Changing insulin strength, maker, type, injection site or method can push blood sugar too high or too low. Injecting repeatedly into areas of lipodystrophy or skin amyloid can raise blood sugar, and suddenly switching to an unaffected area can lower it. Changes are made under close medical supervision.
Overdose from medication errors. Xultophy contains two drugs. More than 50 units a day can mean an overdose of liraglutide (above its 1.8 mg maximum). Mix-ups with other insulins have happened, so the label is checked before each injection, and Xultophy is not used with other GLP-1 receptor agonists.
Low blood sugar. Hypoglycemia is the most common reaction with insulin products and can be life-threatening. It can affect concentration and reaction time. Xultophy is not used during a low blood sugar episode, and the long action of insulin degludec may slow recovery from a low.
Kidney injury from fluid loss. Acute kidney injury, sometimes needing dialysis, has been reported with liraglutide, mostly after dehydration from nausea, vomiting or diarrhea. Kidney function is checked in people with these reactions.
Severe stomach and gut reactions. Stomach and gut reactions, sometimes severe, have been reported. Xultophy is not recommended for people with severe gastroparesis.
Allergic reactions. Severe, life-threatening allergy, including anaphylaxis and angioedema, can occur with insulins, including Xultophy. If a reaction happens, Xultophy is stopped. Caution applies for anyone who had these reactions with another GLP-1 receptor agonist.
Gallbladder disease. In the LEADER trial, 3.1% on liraglutide vs 1.9% on placebo had an acute gallbladder event such as gallstones or inflammation. If gallstones are suspected, the label calls for gallbladder tests.
Low potassium. Insulin moves potassium into cells and can cause hypokalemia, which untreated can be life-threatening. Potassium is checked in people at risk.
Fluid retention and heart failure with TZDs. Thiazolidinediones (such as pioglitazone) can cause fluid retention with insulin products, which may lead to or worsen heart failure. People on both are watched for heart failure signs.
Breathing in stomach contents during anesthesia. Xultophy slows stomach emptying. Rare cases of pulmonary aspiration under general anesthesia or deep sedation have been reported with GLP-1 receptor agonists. The label says to tell the care team about Xultophy before any planned procedure.
From the Medication Guide that comes with Xultophy:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.