Soliqua 100/33 (Sanofi Aventis) is a premixed combination of two drugs - Insulin glargine and Lixisenatide. Insulin glargine is basal insulin while Lixisenatide is a GLP-1 agonist. Soliqua 100/33 is available as a prefilled syringe that contains 3 ml of the solution. Each and every ml of the solution has 100 units of insulin glargine and 33 mcg of Lixisenatide.

It is recommended for the treatment of Diabetes Mellitus Type 2, as an adjunct to diet and exercise, in patients who do not achieve the target blood glucose levels despite using Lixisenatide or basal insulin of fewer than 60 units per day.

Soliqua is not recommended in patients with Type 1 Diabetes Mellitus, patients with Diabetic Ketoacidosis, and those with a history of pancreatitis. It should also be avoided in patients with gastroparesis and has not been studied in prandial insulin.

The concomitant use of another GLP-1 agonist (or another product containing Lixisenatide) or basal insulin (or another product containing glargine insulin) should be avoided. Another similar combination of a Basal Insulin and GLP-1 agonist is Xultophy which contains Insulin Degludec and Liraglutide. 

Soliqua use in Adults:

Soliqua (Insulin glargine and Lixisenatide) Dosing in the treatment of Diabetes mellitus Type 2:

Note:

Patients must discontinue treatment with a GLP-1 agonist, DPP-IV inhibitor, or basal insulin when initiating treatment with Insulin Glargine and Lixisenatide.

• Initial Soliqua dosing:

  • Patients who are currently using 30 to 60 units of basal insulin/day, with or without a GLP-1 agonist:

    • 30 units (insulin glargine 30 units/ lixisenatide 10 mcg) once a day.

  • Patients who are not using a GLP-1 agonist or basal insulin or those patients using basal insulin < 30 units per day or using a GLP-1 agonist alone:

    • 15 units (insulin glargine 15 units/ lixisenatide 5 mcg) once a day.

• Dose titration:

  • The dose should be titrated upwards or downwards by 2 to 4 units of insulin glargine 2 to 4 units/ lixisenatide 0.66 to 1.32 mcg) at weekly intervals until the target blood sugars are achieved;
  • The typical daily dosage is between 15 units of insulin glargine/lixisenatide (5 mcg) and 60 units of insulin glargine/lixisenatide (20 mcg).

• Soliqua Max Dose:

  • The maximum dose is 60 units (insulin glargine 60 units/ lixisenatide 20 mcg) per day

• Missed dose:

  • Doubling the dose or increasing the dose is not recommended.

  • In case, a dose is missed, the next dose should be administered at the recommended scheduled time.

Guide for Dosing Soliqua

FDA dosing guide can be viewed here

The usual starting dose is 15 units/ 5 mcg in Soliqua naive patients or patients using 30 units of insulin glargine or less. Patients using insulin glargine in a dose of 30 - 60 units may be initiated directly on 30 units of the drug. A test dose of 2 units may be administered.

Dosing in Children:

The safety and efficacy of the drug in children are not established.

Pregnancy Risk Category: C

• Hyperglycemia may also be associated with adverse fetal outcomes, however, since effective alternative treatments are available, it should be avoided.
• Animal studies have shown adverse fetal outcomes.

Use during breastfeeding:

• Both endogenous and exogenous insulins are excreted into breast milk.
• The manufacturer recommends weighing the risks of drug exposure in the infant and the benefits of treating the mother.

Soliqua dosing in renal impairment:

• eGFR ≥ 15 to <90 mL/minute/1.73 m²:

  • With renal impairment, drug exposure is increased which may necessitate a dose adjustment.
  • The manufacturer has not recommended any specific dose adjustment.

• eGFR <15 mL/minute/1.73 m²:

  • The drug is not recommended in patients with ESRD.

Soliqua dosing in liver disease:

• Patients with liver disease should have frequent blood sugar monitoring done as insulin clearance and metabolism is altered in these patients.
• Patients may need a dose adjustment.

Common Side Effects of Soliqua (Insulin glargine and lixisenatide):

• Endocrine & metabolic:

  • Hypoglycemia

• Immunologic:

  • Antibody development

Less Common Side Effects of Soliqua (Insulin glargine and lixisenatide):

• Central nervous system:

  • Headache

• Local:

  • Injection site reaction

• Endocrine & metabolic:

  • Severe hypoglycemia

• Respiratory:

  • Nasopharyngitis
  • Upper respiratory tract infection

• Gastrointestinal:

  • Diarrhea

  • Vomiting
  • Nausea

Side effects of Soliqua with frequency unknown:

• Local:

  • Hypertrophy at the injection site
  • Lipoatrophy at the injection site

Contraindications to Soliqua (Insulin glargine and lixisenatide):

• Allergic reaction to insulin glargine, lixisenatide, or any component of the formulation
• Administration during an episode of hypoglycemia

Warnings and Precautions

• Antibody formation:

  • In clinical studies, antibody formation against lixisenatide was noted.
  • The manufacturer, therefore, recommends switching to alternate medications in patients who are not achieving glycemic targets or those who develop hypersensitivity reactions.
  • 2.4% of the patients developed high tigers of these antibodies that resulted in glycemic deregulation and an attenuated response to the drug.
  • Patients who developed these antibodies were more likely to develop hypersensitivity reactions.

• Hypersensitivity:

  • Serious allergic reactions including angioedema and anaphylaxis have been documented with the use of the drug.
  • Patients who have had a prior allergic reaction to lixisenatide or insulin glargine are especially at risk of developing serious reactions.
  • Cross-reactions between GLP-1 agonists are not known.
  • If an allergic reaction is observed, treatment should be immediately stopped and the patient should be appropriately treated.

• Hypoglycemia:

  • Since this is a combination of GLP-1 and insulin glargine.
  • Insulin glargine, like all other insulin, can result in hypoglycemia.
  • Patients may develop drowsiness, seizures, unconsciousness, and even die of prolonged hypoglycemia.
  • Patients who are at risk of hypoglycemia include the elderly, those with renal or liver dysfunction, excessive workout, anorexia, and other concomitant endocrine disorders.
  • Recovery from Hypoglycemia may be delayed with long-acting insulin-like glargine.
  • Patients should be educated about the symptoms of hypoglycemia.
  • Given that hypoglycemia is frequent in these patients, patients must also be advised to refrain from or consume alcohol in moderation.

• Hypokalemia:

  • Insulin causes a shift of potassium into the cells resulting in hypokalemia.
  • Hypokalemia may be severe enough to cause serious ventricular arrhythmias, respiratory and limb paralysis, and even death.
  • Patients who are at risk of developing hypokalemia include those with diarrheal disease and patients on loop diuretics.
  • These patients should be observed for the signs and symptoms of hypokalemia and potassium replacement may be necessary.

• Pancreatitis:

  • Pancreatitis is linked to the usage of GLP-1 agonists, especially lixisenatide.
  • There have been cases of acute pancreatitis, including hemorrhagic and necrotizing pancreatitis.
  • Patients with a prior history of pancreatitis or those with a history of hepatobiliary disease should not be prescribed the drug.
  • If any patient taking lixisenatide or another GLP-1 agonist experiences upper abdomen pain and perhaps even epigastric pain radiating to the back along with nausea or vomiting, they should be instructed to seek emergency medical assistance.
  • Patients should be asked to discontinue the medicine and should be appropriately evaluated and managed.
  • For diabetes, medicines other than GLP-1 agonists and DPP-IV inhibitors should be used.

• Bariatric surgery:

  • Dehydration:

    • Patients may develop acute renal failure or develop worsening of the pre-existing renal disease due to dehydration following bariatric surgery.
    • Patients should be hydrated prior to treatment initiation and should be closely monitored for renal dysfunction.
    • Nausea and dyspepsia are common following gastric bypass, sleeve gastrectomy, and gastric band ligation.
    • Treatment with lixisenatide may add up to gastrointestinal upset resulting in dehydration.

  • Excessive glucagon-like peptide-1 exposure:

    • Both Lixisenatide and Bariatric surgery significantly increase GLP-1 levels.
    • Lixisenatide is an exogenous source of GLP-1 while bariatric surgery increases the endogenous GLP-1 levels.
    • This could predispose the patient to the risks of acute pancreatitis and hypoglycemia.
    • Both gastric bypasses as well as sleeve gastrectomy raise the levels of the endogenous GLP-1 agonists, but not after gastric band ligation.
    • Patients who undergo bariatric surgery (gastric bypass and sleeve gastrectomy, but not gastric banding) may not need exogenous GLP-1 agonists.

  • Hypoglycemia:

    • After bariatric surgery, patients may require fewer medicines to control their diabetes.
    • A reduction of up to 75% of the diabetes medicines may be necessary to avoid episodes of hypoglycemia.
    • Drugs with low hypoglycemic potential should be ideally prescribed.
    • Due to improved insulin secretion and sensitivity, gastric bypass is the procedure with the highest rate of hypoglycemia, followed by sleeve gastrectomy and gastric banding.
    • Other causes of improvement of glycemic control could be a result of weight loss, an increase in insulin sensitivity, and anorexia.
    • Insulin secretion and sensitivity improve in patients with baseline Beta-cell reserves as evidenced by pre-surgery C-peptide levels of > 3 nmol/l.
    • Patients' doses should be adjusted while in the hospital to guide discharge medicine.

  • Weight gain:

    • Alternative therapies may be considered because of the risk of weight regain after bariatric surgery.

• Cardiac disease:

  • Peroxisome proliferator-activated receptor gamma and insulin usage together may increase fluid retention.
  • This could lead to heart failure.
  • Patients who are on concomitant PPAR gamma agonists such as pioglitazone should be monitored for the clinical features of heart failure.
  • Patients at risk of heart failure should discontinue the treatment or reduce the dose of PPAR gamma agonists.

• Gastroparesis:

  • Lixisenatide, like other GLP-1 agonists, causes a slowing of stomach motility.
  • Its use is therefore not recommended in patients with pre-existing gastroparesis

• Renal impairment:

  • Patients with end-stage renal failure (eGFR less than 15 ml/min) shouldn't use lixisenatide.
  • Exposure to the medicine may dramatically increase in people who have mild to severe renal impairment (eGFR of 15 to 30 ml/minute). These individuals should receive dose adjustments and routine blood glucose and renal function monitoring.
  • Dehydration, acute kidney injury, and worsening of pre-existing renal failure may be more common in patients with mild to moderate renal impairment (eGFR of 30 to 90 ml/min). These individuals experience increased drug-related gastrointestinal side effects, such as dehydration-causing nausea, vomiting, and diarrhea.

• Hepatic impairment:

  • Adjustment in the dose is necessary for patients with liver disease.

  • It should be used with caution in patients with liver disease.

Insulin glargine and lixisenatide: Drug Interaction

Monitoring Parameters:

Diabetes mellitus:

• Monitor blood glucose levels
• Glycated hemoglobin at 3 - 6 months intervals.
• Serum potassium
• Liver and renal functions
• weight
• clinical features of pancreatitis
• observe for drug allergy
• Monitor for gastrointestinal-related side effects such as nausea, vomiting, and diarrhea.

How to administer Soliqua (Insulin glargine and lixisenatide)?

• Soliqua should only be administered SubQ.
• IM, IV, or administration via an insulin infusion pump should be avoided.
• It can be injected into the upper arm, thigh, or anterior abdomen. To prevent cutaneous amyloidosis and localized lipodystrophy, the injection site should be rotated.
• Injection into the area of lipodystrophy may alter the glucose-lowering response of the drug.
• It should be given every day at the same time, ideally within an hour of the morning meal.
• Cold solutions should not be injected. Likewise, solutions that are cloudy, discolored, and contain particulate matter should not be administered.
• The solution should not be mixed with other injections or insulin and should not be diluted.
• The dose can be titrated at weekly intervals. The prefilled injections dial in an increment of one unit per click.

Mechanism of action of Soliqua (Insulin glargine and Lixisenatide):

Soliqua is a combination of two drugs, Insulin glargine and Lixisenatide. Insulin glargine is long-acting basal insulin with a duration of action between 24 to 30 hours. It regulates glucose, protein, and fat metabolism.

See Insulin Glargine for more details.

GLP-1 is activated by lixisenatide. It increases insulin sensitivity, slows stomach emptying, reduces glucagon secretion, and encourages glucose-dependent insulin secretion. The drug's elimination half-life is around 3 hours, and it takes the drug between 1 and 3.5 hours to reach its peak plasma levels.

International Brands of Insulin glargine and lixisenatide:

• Soliqua

Soliqua Price in the US:

One pen-injector of 3 ml (33 mcg of lixisenatide and 100 units of glargine per milliliter) costs $58.86 

Insulin glargine and lixisenatide Brand Names in Pakistan:

No Brands are Available in Pakistan.