SOLIMIX

  • For adult patients uncontrolled on basal insulin* + OADs† as an adjunct to diet and exercise

    achIeved noninferiority (primary) and statistically superior (secondary) reduction in A1C vs premix biasp 30 at week 261

    Reduction in A1C from baseline to Week 26

    • SOLIQUA 100/33 met the primary endpoint that demonstrated noninferiority in A1C reduction vs premix BIAsp 30 at Week 26
    • Mean baseline A1C: 8.6%
    • In the SoliMix clinical trial, the final total mean daily insulin dose at Week 26 was 39.7 Units for SOLIQUA 100/33 and 58.2 Units for premix BIAsp 30
    • 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
    • Limitations: open-label design; only studied against the most frequently used premix insulin ratio (30:70), but not against other ratios; last few weeks of the trial were conducted during the COVID-19 pandemic
    • Statistical superiority may not necessarily imply a clinically meaningful difference
    *Insulin glargine 100 Units/mL, NPH, insulin glargine 300 Units/mL, insulin detemir, and insulin degludec.
    †Metformin ± SGLT2 inhibitor.
    ‡Calculated using a noninferiority margin of 0.3%.
    SEE STUDY DESIGN
    EXPLORE SAFETY

      The first head-to-head study to evaluate the efficacy and safety of SOLIQUA 100/33 vs premix BIAsp 30§ as an adjunct to diet and exercise

      In the SoliMix clinical trial, 887 adults with T2DM participated in a 26-week randomized, open-label trial comparing SOLIQUA 100/33 vs premix BIAsp 30.

      • Participants were randomized to SOLIQUA 100/33 (n=443) or premix BIAsp 30 (n=444). Existing OADs continued
      • The final mean daily insulin dose was 39.7 Units for SOLIQUA 100/33 and 58.2 Units for premix BIAsp 30
      • SOLIQUA 100/33 was injected once daily within the hour before a meal; the study did not require that the injection be taken within the hour before the first meal of the day as specified in the Prescribing Information
      • Inclusion criteria
        • T2DM ≥1 year
        • A1C ≥7.5% to ≤10% despite stable doses of basal insulin + OADs for 3 months
        • Insulin glargine 100 Units/mL, NPH, insulin glargine 300 Units/mL, insulin detemir, or insulin degludec
        • Metformin ± SGLT2 inhibitor
      • Primary endpoints at Week 26:
        • SOLIQUA 100/33 was noninferior in A1C reduction vs premix BIAsp 30
        • SOLIQUA 100/33 was superior in weight change vs premix BIAsp 30
      • Key secondary endpoints at Week 26:
        • ​​​​​​​Patients reaching A1C <7% without weight gain
        • Patients reaching A1C <7% without weight gain and without hypoglycemia (PG <70 mg/dL)
        • Superiority of SOLIQUA 100/33 in A1C reduction vs premix BIAsp 30
           

      CI, confidence interval; LS, least squares; NPH, neutral protamin hagedorn; OAD, oral antidiabetic therapy; PG, plasma glucose; SGLT2, sodium glucose cotransporter 2.

      §Premix insulin analog, biphasic insulin aspart (BIAsp) 70/30.

      When A1C is high, the ADA recommends the transition to a basal insulin plus a GLP-1 RA to get A1C down4

      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 adult patients uncontrolled on basal insulin* + OADs† as an adjunct to diet and exercise

    IN THE SOLIMIX PIVOTAL TRIAL, More adult patients got to A1C goal (<7%) without weight gain vs premix BIAsp 301

    Percent of patients reaching A1C <7% without weight gain at Week 26

    • Mean baseline A1C: 8.6%
    • In the SoliMix clinical trial, the final total mean daily insulin dose at Week 26 was 39.7 Units for SOLIQUA 100/33 and 58.2 Units for premix BIAsp 30
    • 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
    • Limitations: open-label design; only studied against the most frequently used premix insulin ratio (30:70), but not against other ratios; last few weeks of the trial were conducted during the COVID-19 pandemic

    *Insulin glargine 100 Units/mL, NPH, insulin glargine 300 Units/mL, insulin detemir, and insulin degludec.
    †Metformin ± SGLT2 inhibitor.
     

    See dosing for patients on basal insulin.

      The first head-to-head study to evaluate the efficacy and safety of SOLIQUA 100/33 vs premix BIAsp 30§ as an adjunct to diet and exercise

      In the SoliMix clinical trial, 887 adults with T2DM participated in a 26-week randomized, open-label trial comparing SOLIQUA 100/33 vs premix BIAsp 30.

      • Participants were randomized to SOLIQUA 100/33 (n=443) or premix BIAsp 30 (n=444). Existing OADs continued
      • The final mean daily insulin dose was 39.7 Units for SOLIQUA 100/33 and 58.2 Units for premix BIAsp 30
      • SOLIQUA 100/33 was injected once daily within the hour before a meal; the study did not require that the injection be taken within the hour before the first meal of the day as specified in the Prescribing Information
      • Inclusion criteria
        • T2DM ≥1 year
        • A1C ≥7.5% to ≤10% despite stable doses of basal insulin + OADs for 3 months
        • Insulin glargine 100 Units/mL, NPH, insulin glargine 300 Units/mL, insulin detemir, or insulin degludec
        • Metformin ± SGLT2 inhibitor
      • Primary endpoints at Week 26:
        • SOLIQUA 100/33 was noninferior in A1C reduction vs premix BIAsp 30
        • SOLIQUA 100/33 was superior in weight change vs premix BIAsp 30
      • Key secondary endpoints at Week 26:
        • ​​​​​​​Patients reaching A1C <7% without weight gain
        • Patients reaching A1C <7% without weight gain and without hypoglycemia (PG <70 mg/dL)
        • Superiority of SOLIQUA 100/33 in A1C reduction vs premix BIAsp 30
           

      CI, confidence interval; LS, least squares; NPH, neutral protamin hagedorn; OAD, oral antidiabetic therapy; PG, plasma glucose; SGLT2, sodium glucose cotransporter 2.

      §Premix insulin analog, biphasic insulin aspart (BIAsp) 70/30.

      When A1C is high, the ADA recommends the transition to a basal insulin plus a GLP-1 RA to get A1C down4

      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. Rosenstock J, Emral R, Sauque-Reyna L, et al. Advancing therapy in suboptimally controlled basal insulin-treated type 2 diabetes: clinical outcomes with iGlarLixi versus premix BIAsp 30 in the SoliMix randomized controlled trial. Diabetes Care. 2021;44(10):2361-2370. doi:10.2337/dc21-0393
  2. McCrimmon RJ, Al Sifri S, Emral R, et al. Advancing therapy with iGlarLixi versus premix BIAsp 30 in basal insulin-treated type 2 diabetes: design and baseline characteristics of the SoliMix randomized controlled trial. Diabetes Obes Metab. 2021;23(6):1221-1231. doi:10.1111/dom.14354
  3. SOLIQUA 100/33 Prescribing Information.
  4. 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.

 

  • 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. Rosenstock J, Emral R, Sauque-Reyna L, et al. Advancing therapy in suboptimally controlled basal insulin-treated type 2 diabetes: clinical outcomes with iGlarLixi versus premix BIAsp 30 in the SoliMix randomized controlled trial. Diabetes Care. 2021;44(10):2361-2370. doi:10.2337/dc21-0393
  2. McCrimmon RJ, Al Sifri S, Emral R, et al. Advancing therapy with iGlarLixi versus premix BIAsp 30 in basal insulin-treated type 2 diabetes: design and baseline characteristics of the SoliMix randomized controlled trial. Diabetes Obes Metab. 2021;23(6):1221-1231. doi:10.1111/dom.14354
  3. SOLIQUA 100/33 Prescribing Information.
  4. 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