Insulin Glargine / Lixisenatide Side Effects

Medically reviewed by Philip Thornton, DipPharm. Last updated on Feb 16, 2024.

Applies to insulin glargine / lixisenatide: subcutaneous solution.

Precautions

It is very important that your doctor will want to check your progress at regular visits, to make sure that this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

It is very important to follow carefully any instructions from your health care team about:

• Alcohol—Drinking alcohol may cause severe low blood sugar. Discuss this with your health care team.
• Other medicines—Do not take other medicines during the time you are taking insulin glargine and lixisenatide combination unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems.
• Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about diabetes medicine dosing changes that might occur because of lifestyle changes, such as changes in exercise and diet. Furthermore, counseling on contraception and pregnancy may be needed because of the problems that can occur in patients with diabetes during pregnancy.
• Travel—Keep a recent prescription and your medical history with you. Be prepared for an emergency as you would normally. Make allowances for changing time zones and keep your meal times as close as possible to your usual meal times.

In case of emergency—There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to:

• Wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says that you have diabetes and a list of all of your medicines.
• Keep an extra supply of Soliqua® and syringes with needles or injection devices on hand in case high blood sugar occurs.
• Keep some kind of quick-acting sugar handy to treat low blood sugar.
• Have a glucagon kit and a syringe and needle available in case severe low blood sugar occurs. Check and replace any expired kits regularly.

This medicine can cause hypoglycemia (low blood sugar). However, low blood sugar can occur when you use Soliqua® with other medicines, including insulin or sulfonylureas, that can lower blood sugar. Low blood sugar also can occur if you delay or miss a meal or snack, exercise more than usual, drink alcohol, or cannot eat because of nausea or vomiting.

• Symptoms of low blood sugar include anxiety, behavior change similar to being drunk, blurred vision, cold sweats, confusion, cool, pale skin, difficulty with thinking, drowsiness, excessive hunger, fast heartbeat, headache (continuing), nausea, nervousness, nightmares, restless sleep, shakiness, slurred speech, or unusual tiredness or weakness.
• If symptoms of low blood sugar occur, eat glucose tablets or gel, corn syrup, honey, or sugar cubes, or drink fruit juice, non-diet soft drink, or sugar dissolved in water to relieve the symptoms. Also, check your blood for low blood sugar. Glucagon is used in emergency situations when severe symptoms including seizures or unconsciousness occur. Have a glucagon kit available, along with a syringe and needle, and know how to use it. Members of your family should also know how to use it.

This medicine can cause low blood sugar. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your antidiabetic medicine or insulin, changes in insulin regimen, you overeat or do not follow your meal plan, have a fever or infection, or do not exercise as much as usual.

• Symptoms of high blood sugar include blurred vision, drowsiness, dry mouth, flushed, dry skin, fruit-like breath odor, increased urination (frequency and amount), ketones in the urine, loss of appetite, stomachache, nausea, or vomiting, tiredness, trouble breathing (rapid and deep), unconsciousness, or unusual thirst.
• If symptoms of high blood sugar occur, check your blood sugar level and then call your doctor for instructions.

This medicine may cause a serious allergic reaction, including anaphylaxis, which can be life-threatening and requires immediate medical attention. Tell your doctor right away if you have a rash, itching, swelling of the face, tongue, and throat, trouble breathing, or chest pain after you receive the medicine.

Check with your doctor right away if you have confusion, decreased urination, diarrhea, dizziness, dry mouth, fainting, increase in heart rate, lightheadedness, nausea, vomiting, rapid breathing, sunken eyes, thirst, unusual tiredness or weakness, or wrinkled skin. These may be symptoms of a kidney problem.

Pancreatitis (swelling of the pancreas) may occur while you are using this medicine. Tell your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

This medicine may cause low levels of potassium in your blood. Do not use medicines, supplements, or salt substitutes that contain potassium unless you have discussed this with your doctor.

Using this medicine together with other diabetes medicine (eg, pioglitazone, rosiglitazone, Actos®, Actoplus Met®, Avandia®) may cause serious heart problem or edema (fluid retention). Check with your doctor immediately if you are rapidly gaining weight, having chest pain or discomfort, extreme tiredness or weakness, trouble breathing, uneven heartbeat, or excessive swelling of the hands, wrist, ankles, or feet.

Check with your doctor right away if you have gaseous stomach pain, indigestion, recurrent fever, severe nausea or vomiting, stomach fullness, or yellow eyes or skin. These may be symptoms of gallbladder problems (eg, cholelithiasis, cholecystitis).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Other side effects

Some side effects of insulin glargine / lixisenatide 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:

Serious side effects

Along with its needed effects, insulin glargine / lixisenatide 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 glargine / lixisenatide:

For healthcare professionals

Applies to insulin glargine / lixisenatide: subcutaneous solution.

General adverse events

The most commonly occurring adverse reactions with this combination drug include hypoglycemia, allergic reactions, nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, and headache.^[Ref]

Metabolic

• Very common (10% or more): Hypoglycemia (up to 40%)^[Ref]

The rates of hypoglycemia depend on the definition of hypoglycemia. For clinical trials with this drug, severe hypoglycemia was defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Symptomatic hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by a self-monitored plasma glucose value of 70 mg/dL or less. Incidence of severe symptomatic hypoglycemia in 2 trials (n=469 and n=365) was 0% and 1.1% while documented symptomatic hypoglycemia was 25.6% and 40%, respectively.^[Ref]

Renal

• Postmarketing reports: Acute kidney injury^[Ref]

Postmarketing reports of acute kidney injury and worsening renal failure, some requiring hemodialysis, have been received in patients treated with GLP-1 receptor agonists.^[Ref]

GLP-1 receptor agonists

Gastrointestinal

Insulin-glargine-lixisenatide:

• Very common (10% or more): Nausea (10%)
• Common (1% to 10%): Diarrhea
• Frequency not reported: Vomiting, constipation, dyspepsia, gastritis, abdominal pain, flatulence, gastroesophageal reflux disease, abdominal distension, decreased appetite

Lixisenatide:

• Frequency not reported: Pancreatitis^[Ref]

Twenty-one cases of pancreatitis were reported during clinical trials with lixisenatide compared with 14 cases in comparator-treated patients. Cases included acute pancreatitis (n=3), pancreatitis (n=12), chronic pancreatitis (n=5), and edematous pancreatitis (n=1). Some patients had risk factors for pancreatitis, such as a history of cholelithiasis or alcohol abuse. GLP-1 receptor agonists have been associated with acute pancreatitis including fatal and non-fatal hemorrhagic or necrotizing pancreatitis.

Gastrointestinal events occur more frequently at the beginning of therapy.^[Ref]

Hypersensitivity

Insulins:

• Frequency not reported: Severe, life-threatening, generalized allergy including anaphylaxis; generalized skin reactions, angioedema, bronchospasm, hypotension, shock

Lixisenatide:

• Uncommon (0.1% to 1%): Anaphylaxis, allergic reactions
• Frequency not reported: Angioedema^[Ref]

In lixisenatide clinical trials, a higher incidence of allergic reactions occurred in antibody positive patients.^[Ref]

Local

• Common (1% to 10%): Injection site reactions
• Frequency not reported: Lipodystrophy, lipohypertrophy^[Ref]

Injection site reactions occurred in 1.7% of patients during clinical trials. Injection site reactions included injection-site hematoma, pain, hemorrhage, erythema, nodules, swelling, discoloration, pruritus, warmth, and injection-site mass.^[Ref]

Immunologic

Insulin-glargine-lixisenatide:

• Very common (10% or more): Antibody formation (up to 43%)

Lixisenatide:

• Common (1% to 10%): High antibody concentrations with attenuated glycemic response^[Ref]

Following 30 weeks of treatment with insulin glargine-lixisenatide, the incidence of anti-insulin glargine antibodies and anti-lixisenatide antibodies was up to 26.2% and approximately 43%, respectively. In about 93% of patients, anti-insulin glargine antibodies showed cross-reactivity to human insulin.

In lixisenatide clinical trials, pooled analysis has shown that 70% of lixisenatide-treated patients were antibody positive at 24 weeks. A subset (2.4%) with the highest antibody concentration showed an attenuated glycemic response. A higher incidence of allergic reactions and injection-site reactions occurred in antibody positive patients.^[Ref]

Cardiovascular

Insulin Glargine:

• Frequency not reported: Peripheral edema^[Ref]

Some patients have experienced edema while taking insulin glargine, especially if previously poor metabolic control was improved by intensified insulin therapy.^[Ref]

Nervous system

• Common (1% to 10%): Headache^[Ref]

Respiratory

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

See also:

Frequently asked questions

• What are the different types of insulin?
• What is the difference between Soliqua and Xultophy?

Further information

Insulin glargine/lixisenatide side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

Medical Disclaimer