Applies to insulin glargine / lixisenatide: subcutaneous solution.
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:
Incidence not known
- Agitation
- bloating
- blurred vision
- chest tightness
- chills
- cold sweats
- cold, clammy skin
- coma
- confusion
- constipation
- cool, pale skin
- cough
- decreased urine output
- difficulty swallowing
- dizziness
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- dry mouth
- fainting
- fast heartbeat
- fast, weak pulse
- fever
- flushed, dry skin
- fruit-like breath odor
- gaseous stomach pain
- headache
- hives, itching, or rash
- hostility
- increased hunger
- increase in heart rate
- increased thirst
- increased urination
- indigestion
- irregular heartbeat
- irritability
- large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
- lethargy
- lightheadedness
- loss of appetite
- muscle pain or cramps
- muscle twitching
- nausea or vomiting
- nightmares
- noisy breathing
- numbness or tingling in the hands, feet, or lips
- pains in the stomach, side, or abdomen, possibly radiating to the back
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- rapid breathing
- rapid weight gain
- seizures
- slurred speech
- stomach pain or fullness
- stupor
- sunken eyes
- sweating
- thirst
- trouble breathing
- unexplained weight loss
- unusual tiredness or weakness
- wrinkled skin
- yellow eyes or skin
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:
More common
- Body aches or pain
- diarrhea
- ear congestion
- loss of voice
- muscle aches
- sneezing
- sore throat
- stuffy or runny nose
Incidence not known
- Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
For Healthcare Professionals
Applies to insulin glargine / lixisenatide: subcutaneous solution.
General
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
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]
Very common (10% or more): Hypoglycemia (up to 40%)[Ref]
Renal
GLP-1 receptor agonists
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]
Gastrointestinal
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]
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]
Hypersensitivity
In lixisenatide clinical trials, a higher incidence of allergic reactions occurred in antibody positive patients.[Ref]
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]
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]
