LIXILAN-L

  • For adult patients with T2DM uncontrolled on basal insulin as an adjunct to diet and exercise

    IN THE LIXILAN-L PIVOTAL TRIAL, Soliqua 100/33 demonstrated ~2X  greater A1C reduction vs Lantus®1

    • In the LixiLan-L clinical trial at Week 30, the 1.1% mean reduction in A1C from baseline with SOLIQUA 100/33 was ~2X greater than the 0.6% reduction with Lantus
    • The mean final dose of SOLIQUA 100/33 and Lantus at Week 30 was equivalent: 46.7 Units (for SOLIQUA 100/33: 46.7 Units insulin glargine/15.6 mcg lixisenatide)
    • The difference in effect observed in the trial may not necessarily reflect the effect that will be observed in the care setting where alternative insulin glargine dosage can be used
    SEE STUDY DESIGN
    EXPLORE SAFETY

      Designed to evaluate the efficacy and safety of SOLIQUA 100/33 vs Lantus as an adjunct to diet and exercise

      In the LixiLan-L clinical trial, a total of 736 patients with T2DM participated in a randomized, 30-week, open-label, multicenter study to evaluate the efficacy and safety of SOLIQUA 100/33 compared to Lantus.

      • Adults with T2DM, mean age 60 years, uncontrolled on a stable daily basal insulin dose ±1 or 2 oral antidiabetic drugs (OADs) for ≥6 months (A1C of 7.5%-10%; fasting plasma glucose [FPG] ≤180 mg/dL) were screened
      • Eligible patients (n=1018) were enrolled in a 6-week run-in period where they remained on or were switched to Lantus if on another basal insulin, and had their dose titrated/stabilized while continuing on metformin (if previously taken). Any other OADs were discontinued
      • Patients inadequately controlled at the end of the run-in period (n=736; A1C between 7% and 10%; FPG ≤140 mg/dL) and on an insulin glargine dose of 20-50 Units (mean dose of 35 Units) were randomized to either SOLIQUA 100/33 (n=367) or Lantus (n=369)
      • The primary endpoint was change from baseline A1C at week 30
      • The maximum allowable insulin glargine dose was 60 Units for both treatment groups
      • The trial was designed to show the contribution of the GLP-1 RA component to glycemic lowering, and the insulin glargine dose and the dosing algorithm were selected to isolate the effect of the GLP-1 RA component

      When A1C is high, the ADA recommends the transition to a basal insulin plus a GLP-1 RA* to get A1C down2

      The 2022 ADA Guidelines recommend initial injectable combinations, such as basal insulin plus a GLP-1 RA, when A1C is ≥1.5% above target.

  • For patients with A1C >9%

    IN THE LIXILAN-L PIVOTAL TRIAL, More T2DM patients got below 7% with SOLIQUA 100/333,4*

    >9.0% needs powerful A1C reduction

    *as an adjunct to diet and exercise.

    • Analysis description: LixiLan-L clinical trial post hoc analysis of patients who completed the 6-week run-in phase (treatment with Lantus only) and completed the 30-week treatment phase (patients randomized to remain on Lantus or switch to SOLIQUA 100/33)3

    • Analysis limitations: Patients who used rescue therapy or discontinued treatment early (including 40 SOLIQUA 100/33 patients and 34 Lantus patients) were not included. P values are for descriptive purposes only3

    • The difference in effect observed in the trial may not necessarily be reflected in the care setting where alternative insulin glargine dosage can be used

      Designed to evaluate the efficacy and safety of SOLIQUA 100/33 vs Lantus

      In the LixiLan-L clinical trial, a total of 736 patients with T2DM participated in a randomized, 30-week, open-label, multicenter study to evaluate the efficacy and safety of SOLIQUA 100/33 compared to Lantus.

      • Adults with T2DM, mean age 60 years, uncontrolled on a stable daily basal insulin dose ±1 or 2 oral antidiabetic drugs (OADs) for ≥6 months (A1C of 7.5%-10%; fasting plasma glucose [FPG] ≤180 mg/dL) were screened
      • Eligible patients (n=1018) were enrolled in a 6-week run-in period where they remained on or were switched to Lantus if on another basal insulin, and had their dose titrated/stabilized while continuing on metformin (if previously taken). Any other OADs were discontinued
      • Patients inadequately controlled at the end of the run-in period (n=736; A1C between 7% and 10%; FPG ≤140 mg/dL) and on an insulin glargine dose of 20-50 Units (mean dose of 35 Units) were randomized to either SOLIQUA 100/33 (n=367) or Lantus (n=369)
      • The primary endpoint was change from baseline A1C at week 30
      • The maximum allowable insulin glargine dose was 60 Units for both treatment groups
      • The trial was designed to show the contribution of the GLP-1 RA component to glycemic lowering, and the insulin glargine dose and the dosing algorithm were selected to isolate the effect of the GLP-1 RA component

      When A1C is high, the ADA recommends the transition to a basal insulin plus a GLP-1 RA to get A1C down2

      The 2022 ADA Guidelines recommend initial injectable combinations, such as basal insulin plus a GLP-1 RA, when A1C is ≥1.5% above target.

  • For patients with A1C >9% as an adjunct to diet and exercise

    IN THE LIXILAN-L PIVOTAL TRIAL, More T2DM patients got below 7% with SOLIQUA 100/333,4

    Additional A1C results from this study

    • Analysis description: LixiLan-L clinical trial post hoc analysis of patients who completed the 6-week run-in phase (treatment with Lantus only) and completed the 30-week treatment phase (patients randomized to remain on Lantus or switch to SOLIQUA 100/33)3
    • Analysis limitations: Patients who used rescue therapy or discontinued treatment early (including 40 SOLIQUA 100/33 patients and 34 Lantus patients) were not included. P values are for descriptive purposes only3
    • The difference in effect observed in the trial may not necessarily be reflected in the care setting where alternative insulin glargine dosage can be used5

      Designed to evaluate the efficacy and safety of SOLIQUA 100/33 vs Lantus

      In the LixiLan-L clinical trial, a total of 736 patients with T2DM participated in a randomized, 30-week, open-label, multicenter study to evaluate the efficacy and safety of SOLIQUA 100/33 compared to Lantus.

      • Adults with T2DM, mean age 60 years, uncontrolled on a stable daily basal insulin dose ±1 or 2 oral antidiabetic drugs (OADs) for ≥6 months (A1C of 7.5%-10%; fasting plasma glucose [FPG] ≤180 mg/dL) were screened
      • Eligible patients (n=1018) were enrolled in a 6-week run-in period where they remained on or were switched to Lantus if on another basal insulin, and had their dose titrated/stabilized while continuing on metformin (if previously taken). Any other OADs were discontinued
      • Patients inadequately controlled at the end of the run-in period (n=736; A1C between 7% and 10%; FPG ≤140 mg/dL) and on an insulin glargine dose of 20-50 Units (mean dose of 35 Units) were randomized to either SOLIQUA 100/33 (n=367) or Lantus (n=369)
      • The primary endpoint was change from baseline A1C at week 30
      • The maximum allowable insulin glargine dose was 60 Units for both treatment groups
      • The trial was designed to show the contribution of the GLP-1 RA component to glycemic lowering, and the insulin glargine dose and the dosing algorithm were selected to isolate the effect of the GLP-1 RA component

      When A1C is high, the ADA recommends the transition to a basal insulin plus a GLP-1 RA* to get A1C down5

      The 2022 ADA Guidelines recommend initial injectable combinations, such as basal insulin plus a GLP-1 RA, when A1C is ≥1.5% above target.

SOLIQUA 100/33 is a combination of a long-acting human insulin analog with a glucagon-like peptide-1 (GLP-1) receptor agonist (RA) indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
 

Limitations of Use:
 

  • Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
  • Not recommended for use in combination with any other product containing a GLP-1 receptor agonist.
  • Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
  • Not recommended for use in patients with gastroparesis.
  • Has not been studied in combination with prandial insulin.

Important Safety Information

Important Safety Information for SOLIQUA 100/33 (insulin glargine and lixisenatide) injection 100 Units/mL and 33 mcg/mL

Contraindications

  • During episodes of hypoglycemia.
  • In patients with known serious hypersensitivity to insulin glargine, lixisenatide, or to any of the product components.

 

Warnings and Precautions

  • Anaphylaxis and Serious Hypersensitivity Reactions: In clinical trials of lixisenatide, there have been cases of anaphylaxis and other serious hypersensitivity reactions including angioedema. Severe, life-threatening, generalized allergic reactions, including anaphylaxis and angioedema, can occur with insulins, including insulin glargine. There have been reports of serious hypersensitivity reactions, including anaphylactic reactions and angioedema, in patients treated with SOLIQUA 100/33. If hypersensitivity reactions occur, discontinue SOLIQUA 100/33. Use caution in patients with a history of anaphylaxis or angioedema with another GLP-1 RA because it is unknown whether such patients will be predisposed to anaphylaxis.

 

  • Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 RAs. Cases of pancreatitis were reported in clinical trials of lixisenatide. After initiation of SOLIQUA 100/33, observe patients for signs and symptoms of pancreatitis (e.g., persistent severe abdominal pain, sometimes radiating to the back and which may be accompanied by vomiting). If pancreatitis is suspected, SOLIQUA 100/33 should promptly be discontinued. If pancreatitis is confirmed, restarting SOLIQUA 100/33 is not recommended and other antidiabetic therapies should be considered.

 

  • Never Share a SOLIQUA 100/33 SoloStar® Pen between Patients: Pen-sharing poses a risk for transmission of blood-borne pathogens, even if the needle is changed.

 

  • Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in insulin regimen including, strength, manufacturer, type, injection site or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Changes should be made cautiously, and the frequency of blood glucose monitoring should be increased. Adjustments in concomitant oral antidiabetic treatment may be needed.

    Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis may result in hyperglycemia; sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia. Advise patients to rotate injection site to unaffected areas and closely monitor for hypoglycemia.

 

  • Medication Errors: SOLIQUA 100/33 contains two drugs. Do not administer more than 60 units of SOLIQUA 100/33, which may result in overdose of the lixisenatide component. Do not use other GLP-1 RAs. Accidental mix-ups between insulin products have been reported. Instruct patients to always check the label before administration. Do not withdraw SOLIQUA 100/33 from the pen with a syringe.

 

  • Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulin-containing therapy, which may be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity, and in patients with renal or hepatic impairment and hypoglycemia unawareness.

 

  • Acute Kidney Injury: There have been reports of acute renal failure and worsening of chronic failure, which may sometimes require hemodialysis in patients treated with SOLIQUA 100/33. Some of these events were reported in patients without known underlying renal disease. Most reports occurred in patients who experienced nausea, vomiting, diarrhea, or dehydration; advise patients to take precautions to avoid fluid depletion. Monitor blood glucose and renal function in patients with renal impairment. SOLIQUA 100/33 is not recommended in patients with end-stage renal disease.

 

  • Immunogenicity: Patients may develop antibodies to insulin and lixisenatide. If there is worsening glycemic control or failure to achieve targeted glycemic control, significant injection site reactions or allergic reactions, then other antidiabetic therapy should be considered.

 

  • Hypokalemia: All insulin containing products can cause hypokalemia, which may be life-threatening. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated.

 

  • Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) and insulin. These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of TZD must be considered.

 

  • Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and post-marketing. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.

 

Most Common Adverse Reactions

The most common adverse reactions reported in ≥ 5% of patients treated with SOLIQUA 100/33 include hypoglycemia, nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, headache
 

 

Drug Interactions

  • Certain drugs may affect glucose metabolism, requiring dose adjustment of SOLIQUA 100/33 and close monitoring of blood glucose.
  • The signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs (eg, beta-blockers, clonidine, guanethidine, and reserpine).
  • The lixisenatide in SOLIQUA 100/33 delays gastric emptying, which may reduce the rate of absorption of orally administered medication with a narrow therapeutic ratio or that require careful clinical monitoring. If such medications are to be administered with food, do not co-administer with SOLIQUA 100/33.
  • Antibiotics, acetaminophen, or other medications that are dependent on threshold concentrations for efficacy, or where a delay in effect is undesirable, should be administered at least 1 hour before SOLIQUA 100/33 injection.
  • Oral contraceptives should be taken at least 1 hour before SOLIQUA 100/33 administration or 11 hours after.

 

Click here for full Prescribing Information.

Click here for information on Sharps Medical Waste Disposal.

Click here to learn more about Sanofi’s commitment to fighting counterfeit drugs.

 

References:

  1. SOLIQUA 100/33 Prescribing Information.
  2. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes—2022. Diabetes Care. 2022;45(suppl 1):S125-S143.
    doi:10.2337/dc22-S009
  3. Niemoeller E, Souhami E, Wu Y, Jensen KH. iGlarLixi reduces glycated hemoglobin to a greater extent than basal insulin regardless of levels at screening: post hoc analysis of LixiLan-L. Diabetes Ther. 2018;9:373-382. doi.org/10.1007/s13300-017-0336-6
  4. Data on file. Additional Data A1C after run-in. July 2018.
  5. Davies MJ, Russell-Jones D, Barber TM, et al. Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial. Diabetes Obes Metab. 2019;21:1967–1972. doi:10.1111/dom.13791

Important Safety Information

Important Safety Information for SOLIQUA 100/33 (insulin glargine and lixisenatide) injection 100 Units/mL and 33 mcg/mL

Contraindications

  • During episodes of hypoglycemia.
  • In patients with known serious hypersensitivity to insulin glargine, lixisenatide, or to any of the product components.

 

Warnings and Precautions

  • Anaphylaxis and Serious Hypersensitivity Reactions: In clinical trials of lixisenatide, there have been cases of anaphylaxis and other serious hypersensitivity reactions including angioedema. Severe, life-threatening, generalized allergic reactions, including anaphylaxis and angioedema, can occur with insulins, including insulin glargine. There have been reports of serious hypersensitivity reactions, including anaphylactic reactions and angioedema, in patients treated with SOLIQUA 100/33. If hypersensitivity reactions occur, discontinue SOLIQUA 100/33. Use caution in patients with a history of anaphylaxis or angioedema with another GLP-1 RA because it is unknown whether such patients will be predisposed to anaphylaxis.

 

  • Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 RAs. Cases of pancreatitis were reported in clinical trials of lixisenatide. After initiation of SOLIQUA 100/33, observe patients for signs and symptoms of pancreatitis (e.g., persistent severe abdominal pain, sometimes radiating to the back and which may be accompanied by vomiting). If pancreatitis is suspected, SOLIQUA 100/33 should promptly be discontinued. If pancreatitis is confirmed, restarting SOLIQUA 100/33 is not recommended and other antidiabetic therapies should be considered.

 

  • Never Share a SOLIQUA 100/33 SoloStar® Pen between Patients: Pen-sharing poses a risk for transmission of blood-borne pathogens, even if the needle is changed.

 

  • Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in insulin regimen including, strength, manufacturer, type, injection site or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Changes should be made cautiously, and the frequency of blood glucose monitoring should be increased. Adjustments in concomitant oral antidiabetic treatment may be needed.

    Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis may result in hyperglycemia; sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia. Advise patients to rotate injection site to unaffected areas and closely monitor for hypoglycemia.

 

  • Medication Errors: SOLIQUA 100/33 contains two drugs. Do not administer more than 60 units of SOLIQUA 100/33, which may result in overdose of the lixisenatide component. Do not use other GLP-1 RAs. Accidental mix-ups between insulin products have been reported. Instruct patients to always check the label before administration. Do not withdraw SOLIQUA 100/33 from the pen with a syringe.

 

  • Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulin-containing therapy, which may be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity, and in patients with renal or hepatic impairment and hypoglycemia unawareness.

 

  • Acute Kidney Injury: There have been reports of acute renal failure and worsening of chronic failure, which may sometimes require hemodialysis in patients treated with SOLIQUA 100/33. Some of these events were reported in patients without known underlying renal disease. Most reports occurred in patients who experienced nausea, vomiting, diarrhea, or dehydration; advise patients to take precautions to avoid fluid depletion. Monitor blood glucose and renal function in patients with renal impairment. SOLIQUA 100/33 is not recommended in patients with end-stage renal disease.

 

  • Immunogenicity: Patients may develop antibodies to insulin and lixisenatide. If there is worsening glycemic control or failure to achieve targeted glycemic control, significant injection site reactions or allergic reactions, then other antidiabetic therapy should be considered.

 

  • Hypokalemia: All insulin containing products can cause hypokalemia, which may be life-threatening. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated.

 

  • Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) and insulin. These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of TZD must be considered.

 

  • Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and post-marketing. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.

 

Most Common Adverse Reactions

The most common adverse reactions reported in ≥ 5% of patients treated with SOLIQUA 100/33 include hypoglycemia, nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, headache
 

 

Drug Interactions

  • Certain drugs may affect glucose metabolism, requiring dose adjustment of SOLIQUA 100/33 and close monitoring of blood glucose.
  • The signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs (eg, beta-blockers, clonidine, guanethidine, and reserpine).
  • The lixisenatide in SOLIQUA 100/33 delays gastric emptying, which may reduce the rate of absorption of orally administered medication with a narrow therapeutic ratio or that require careful clinical monitoring. If such medications are to be administered with food, do not co-administer with SOLIQUA 100/33.
  • Antibiotics, acetaminophen, or other medications that are dependent on threshold concentrations for efficacy, or where a delay in effect is undesirable, should be administered at least 1 hour before SOLIQUA 100/33 injection.
  • Oral contraceptives should be taken at least 1 hour before SOLIQUA 100/33 administration or 11 hours after.

 

Click here for full Prescribing Information.

Click here for information on Sharps Medical Waste Disposal.

Click here to learn more about Sanofi’s commitment to fighting counterfeit drugs.

 

References:

  1. SOLIQUA 100/33 Prescribing Information.
  2. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes—2022. Diabetes Care. 2022;45(suppl 1):S125-S143.
    doi:10.2337/dc22-S009
  3. Niemoeller E, Souhami E, Wu Y, Jensen KH. iGlarLixi reduces glycated hemoglobin to a greater extent than basal insulin regardless of levels at screening: post hoc analysis of LixiLan-L. Diabetes Ther. 2018;9:373-382. doi.org/10.1007/s13300-017-0336-6
  4. Data on file. Additional Data A1C after run-in. July 2018.
  5. Davies MJ, Russell-Jones D, Barber TM, et al. Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial. Diabetes Obes Metab. 2019;21:1967–1972. doi:10.1111/dom.13791