LIXILAN-O

  • Adult patients with T2DM uncontrolled on oral antidiabetic therapy (OADs) as an adjunct to diet and exercise

    IN THE LIXILAN-O PIVOTAL TRIAL, SOLIQUA 100/33 SIGNIFICANTLY REDUCED A1C OVER 30 WEEKS1

    Reduction in A1C from baseline to Week 30

    • 74% of patients got to ADA goal (<7%) with SOLIQUA 100/33

      • 33% of GLP-1 RA (lixisenatide) patients and 59% of Lantus patients got to goal
    • In the LixiLan-O clinical trial, the final mean basal insulin daily dose was similar between SOLIQUA 100/33 (39.8 Units) and Lantus (40.5 Units), determined by the FPG titration
    • 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

    *p<0.0001 vs Lantus.

      • Eligible patients (N=1479) were enrolled in a 4-week run-in period during which they stopped taking any second OAD and titrated metformin to 2000 mg/d or maximum tolerated dose (1500 mg/d)2
      • Patients inadequately controlled at the end of the run-in period (N=1170) were randomized to either SOLIQUA 100/33 (n=469), Lantus (n=467), or lixisenatide (n=234) with metformin1
      • Criteria for randomization1,2:
        • A1C between 7% and 10%
        • FPG 250 mg/dL
      • The maximum allowable insulin glargine dose was 60 Units for both the SOLIQUA 100/33 and Lantus treatment groups1

      ADA, American Diabetes Association; FPG, fasting plasma glucose; OAD, oral antidiabetic therapy.

      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.

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

    IN THE LIXILAN-O PIVOTAL TRIAL, SOLIQUA 100/33 REDUCED a1c by 2.9%1,3

    Reduction in A1C from baseline to Week 30

    • In this post hoc subgroup analysis, LixiLan-O patients with A1C ≥9%-10.4% at baseline were evaluated. Doses were similar between SOLIQUA 100/33 (45 Units) and Lantus (44 Units)
    • Analysis limitations: This study was not designed or powered to detect differences between treatments within this subgroup. Analysis included limited sample size, N=134
    • The difference in effect observed in this subgroup analysis may not necessarily reflect the effect that will be observed in the care setting where alternative insulin glargine dosage can be used
      • Eligible patients (N=1479) were enrolled in a 4-week run-in period during which they stopped taking any second OAD and titrated metformin to 2000 mg/d or maximum tolerated dose (1500 mg/d)2
      • Patients inadequately controlled at the end of the run-in period (N=1170) were randomized to either SOLIQUA 100/33 (n=469), Lantus (n=467), or lixisenatide (n=234) with metformin1
      • Criteria for randomization1,2:
        • A1C between 7% and 10%
        • FPG 250 mg/dL
      • The maximum allowable insulin glargine dose was 60 Units for both the SOLIQUA 100/33 and Lantus treatment groups1

      FPG, fasting plasma glucose; OAD, oral antidiabetic therapy.

      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.

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

    IN THE LIXILAN-O PIVOTAL TRIAL, MORE PATIENTS GOT TO ADA GOAL (<7%) WITH SOLIQUA 100/333

    SOLIQUA 100/33 demonstrated a result consistent with the result in the pivotal trial1,3

    • In this post hoc subgroup analysis, LixiLan-O patients with A1C ≥9%-10.4% at baseline were evaluated. Doses were similar between SOLIQUA 100/33 (45 Units) and Lantus (44 Units)2,3
    • Analysis limitations: This study was not designed or powered to detect differences between treatments within this subgroup. Analysis included limited sample size, N=134
    • The difference in effect observed in this subgroup analysis may not necessarily reflect the effect that will be observed in the care setting where alternative insulin glargine dosage can be used1
      • Eligible patients (N=1479) were enrolled in a 4-week run-in period during which they stopped taking any second OAD and titrated metformin to 2000 mg/d or maximum tolerated dose (1500 mg/d)2
      • Patients inadequately controlled at the end of the run-in period (N=1170) were randomized to either SOLIQUA 100/33 (n=469), Lantus (n=467), or lixisenatide (n=234) with metformin1
      • Criteria for randomization1,2:
        • A1C between 7% and 10%
        • FPG 250 mg/dL
      • The maximum allowable insulin glargine dose was 60 Units for both the SOLIQUA 100/33 and Lantus treatment groups1

      FPG, fasting plasma glucose; OAD, oral antidiabetic therapy.

      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.

  • For patients uncontrolled on OADs as an adjunct to diet and exercise

    THE LIXILAN-O PIVOTAL TRIAL IMPROVED GLYCEMIC VALUES throughout the day with SOLIQUA 100/334

    SOLIQUA 100/33 demonstrated greater reduction in mean SMPG concentrations across all time points compared with its individual components alone

    • In this post hoc analysis of the LixiLan-O trial, glycemic variability data with SOLIQUA 100/33 was compared with data from its individual components, lixisenatide and basal insulin glargine
    • Analysis limitations: Data were obtained from SMPG rather than CGM. Only patients with measurements at both baseline and Week 30 were included. Glycemic variability was not the primary endpoint of these trials
    • The difference in effect observed in this post hoc analysis may not necessarily reflect the effect that will be observed in the care setting where alternative insulin glargine dosage can be used

    CGM, continuous glucose monitoring; SMPG, self-measured plasma glucose; OAD, oral antidiabetic therapy.

      • Eligible patients (N=1479) were enrolled in a 4-week run-in period during which they stopped taking any second OAD and titrated metformin to 2000 mg/d or maximum tolerated dose (1500 mg/d)2
      • Patients inadequately controlled at the end of the run-in period (N=1170) were randomized to either SOLIQUA 100/33 (n=469), Lantus (n=467), or lixisenatide (n=234) with metformin1
      • Criteria for randomization1,2:
        • A1C between 7% and 10%
        • FPG 250 mg/dL
      • The maximum allowable insulin glargine dose was 60 Units for both the SOLIQUA 100/33 and Lantus treatment groups1

      FPG, fasting plasma glucose.

      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.

  • Watch Dr. Pettus break down the LixiLan-O study

      • Eligible patients (N=1479) were enrolled in a 4-week run-in period during which they stopped taking any second OAD and titrated metformin to 2000 mg/d or maximum tolerated dose (1500 mg/d)2
      • Patients inadequately controlled at the end of the run-in period (N=1170) were randomized to either SOLIQUA 100/33 (n=469), Lantus (n=467), or lixisenatide (n=234) with metformin1
      • Criteria for randomization1,2:
        • A1C between 7% and 10%
        • FPG 250 mg/dL
      • The maximum allowable insulin glargine dose was 60 Units for both the SOLIQUA 100/33 and Lantus treatment groups1

      FPG, fasting plasma glucose; OAD, oral antidiabetic therapy.

      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.

 

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, and 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. Data on file. CSR 12404. Sanofi US.
  3. 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
  4. Aronson R, Umpierrez G, Stager W, Kovatchev B. Insulin glargine/lixisenatide fixed-ratio combination improves glycaemic variability and control without increasing hypoglycaemia. Diabetes Obes Metab. 2019;21:726-731. doi:10.1111/dom.13580
  5. 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

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.

 

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, and 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. Data on file. CSR 12404. Sanofi US.
  3. 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
  4. Aronson R, Umpierrez G, Stager W, Kovatchev B. Insulin glargine/lixisenatide fixed-ratio combination improves glycaemic variability and control without increasing hypoglycaemia. Diabetes Obes Metab. 2019;21:726-731. doi:10.1111/dom.13580
  5. 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