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Xultophy Side Effects

Generic name: insulin degludec / liraglutide

Medically reviewed by Last updated on Sep 6, 2023.

Note: This document contains side effect information about insulin degludec / liraglutide. Some dosage forms listed on this page may not apply to the brand name Xultophy.

Applies to insulin degludec / liraglutide: subcutaneous solution.


Subcutaneous route (Solution)

Liraglutide, a component of insulin degludec/liraglutide is known to cause dose-dependent and treatment-duration dependent thyroid C-cell tumors in rats and mice. It is unknown whether this component causes thyroid C-cell tumors in humans. Use is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Serious side effects of Xultophy

Along with its needed effects, insulin degludec / liraglutide may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking insulin degludec / liraglutide:

Incidence not known

Other side effects of Xultophy

Some side effects of insulin degludec / liraglutide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Incidence not known

For Healthcare Professionals

Applies to insulin degludec / liraglutide: subcutaneous solution.


The most frequently reported adverse reactions included hypoglycemia and gastrointestinal adverse reactions, such as nausea diarrhea, vomiting, constipation, dyspepsia, gastritis, abdominal pain, flatulence, gastroesophageal reflux disease, and abdominal distention.[Ref]


Common (1% to 10%): Nausea, diarrhea, vomiting, constipation, dyspepsia, gastritis, abdominal pain, flatulence, gastroesophageal reflux disease, abdominal distension, decreased appetite, increased lipase

Uncommon (0.1% to 1%): Pancreatitis, including necrotizing pancreatitis


Postmarketing reports: Acute pancreatitis, hemorrhagic and necrotizing pancreatitis (sometimes resulting in death)[Ref]

Gastrointestinal adverse events occur more frequently at the beginning of therapy and generally diminish within a few days or weeks of continued use. Nausea was transient for most patients.[Ref]


Weight gain may occur and has been attributed to the anabolic effects of insulin. After 26 weeks of insulin degludec / liraglutide 100/3.6, a mean increase of 2 kg occurred.[Ref]

Very common (10% or more): Hypoglycemia

Common (1% to 10%): Decreased appetite

Uncommon (0.1% to 1%): Dehydration

Frequency not reported: Weight gain[Ref]



Frequency not reported: Increased blood calcitonin, goitre[Ref]


Uncommon (0.1% to 1%): Urticaria, rash, pruritus, face swelling

Rare (less than 0.1%): Hypersensitivity manifested with swelling of tongue and lips, diarrhea, nausea, tiredness, and itching

Postmarketing reports: Anaphylactic reaction


Postmarketing reports: Angioedema, anaphylactic reactions, rash, pruritus[Ref]

Hypersensitivity reactions including urticaria, pruritus, and/or swelling of the face have been reported following administration of this drug. Few case of anaphylactic reaction with additional symptoms such as hypotension, palpitations, dyspnea, and edema has been reported postmarketing.[Ref]


Common (1% to 10%): Injection site reaction

Frequency not reported: Lipodystrophy[Ref]

Injection site reactions included injection site hematoma, pain, hemorrhage, erythema, nodules, swelling, discolorations, pruritus, warmth, and injection site mass. These reactions are generally mild and transient, disappearing with continued treatment. Lipodystrophy may occur at the injection site. Rotation of injection site may help reduce the risk of developing these reactions.[Ref]


Mean increase in heart rate of 2 to 3 beats per minute has been observed; long-term clinical effects are unknown.[Ref]

Uncommon (0.1% to 1%): Increased heart rate

Frequency not reported: Peripheral edema[Ref]


Uncommon (0.1% to 1%): Rash, pruritus, urticaria

Insulin degludec:

Postmarketing period: Localized cutaneous amyloidosis[Ref]


Rare (less than 0.1%): Antibody formation[Ref]



Frequency not reported: Temporary worsening of diabetic retinopathy, transitory reversible ophthalmologic refraction disorder[Ref]

Temporary worsening of diabetic retinopathy may occur with abrupt improvement in glycemic control; however, long-term improvement may decrease the risk of progression.[Ref]



Frequency not reported: Thyroid neoplasm, malignant neoplasms

Postmarketing: Medullary thyroid carcinoma[Ref]

Pooled analysis of liraglutide clinical trials reveals the incidence rate for malignant neoplasms at 10.9, 6.3, and 7.2 per 1000 patient-years for liraglutide, placebo, and active comparator treated patients, respectively. Incidence rates were based on investigator-reported events, medical history, pathology reports, and surgical reports from both blinded and open-label studies. Seven cases of papillary thyroid carcinoma were in liraglutide-treated patients and 1 case in a comparator-treated patient. Most were less than 1 cm in greatest diameter and diagnosed in surgical pathology specimens after thyroidectomy prompted by findings on protocol-specified screening with serum calcitonin or thyroid ultrasound. Seven malignant neoplasm events were reported beyond 1-year exposure to study medication: 4 colon, 1 prostate and 1 nasopharyngeal in liraglutide-treated patients with 1 (colon) reported in a comparator-treated patient.[Ref]



Frequency not reported: Renal impairment, acute renal failure

Postmarketing reports: Increased serum creatinine, acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis[Ref]



Common (1% to 10%): Elevated serum bilirubin, cholelithiasis

Uncommon (0.1% to 1%): Cholecystitis

Postmarketing: Cholestasis, hepatitis, elevated liver enzymes, hyperbilirubinemia[Ref]

Cholelithiasis and cholecystitis have been reported in liraglutide trials. In doses of up to 3 mg, cholelithiasis and cholecystitis were reported in 1.5% (vs 0.5%) and 0.6% (vs 0.2%), respectively (compared to placebo). The majority of patients with cholelithiasis and cholecystitis required cholecystectomy. In the cardiovascular outcomes trial, liraglutide-treated patients reported an acute event of gallbladder disease such as cholelithiasis or cholecystitis more frequently than those receiving placebo (3.6% vs 1.9%). Most of these events required hospitalization or cholecystectomy.[Ref]

Nervous system

Common (1% to 10%): Headache

Frequency not reported: Acute painful peripheral neuropathy[Ref]

Acute painful peripheral neuropathy may occur with abrupt improvement in glycemic control; however, long-term improvement may decrease the risk of progression.[Ref]


Common (1% to 10%): Nasopharyngitis, upper respiratory infection[Ref]

Frequently asked questions


1. Cerner Multum, Inc. "UK Summary of Product Characteristics."

2. (2016) "Product Information. Xultophy (insulin degludec-liraglutide)." Novo Nordisk Pharmaceuticals Inc

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.