Basaglar (Insulin Glargine)

BASAGLAR^® is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus.

• Individualize dosage based on metabolic needs, blood glucose monitoring, glycemic control, type of diabetes, prior insulin use. (
  2.2 General Dosing Instructions

  • In patients with type 1 diabetes, BASAGLAR must be used concomitantly with short-acting insulin.
  • Inject BASAGLAR subcutaneously once daily at any time of day but at the same time every day.
  • Individualize and adjust the dosage of BASAGLAR based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
  • Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), during acute illness, or changes in renal or hepatic function. Dosage adjustments should only be made under medical supervision with appropriate glucose monitoring
    [see Warnings and Precautions ]
    .
  • The BASAGLAR prefilled pens each dials in 1 unit increments and delivers a maximum dose of 80 units per injection.
  ,
  2.3 Initiation of BASAGLAR Therapy

  • The recommended starting dose of BASAGLAR in patients with type 1 diabetes should be approximately one-third of the total daily insulin requirements. Short- or rapid-acting, pre-meal insulin should be used to satisfy the remainder of the daily insulin requirements.
  • The recommended starting dose of BASAGLAR in patients with type 2 diabetes is 0.2 units/kg or up to 10 units once daily.
  ,
  2.4 Changing to BASAGLAR from Other Insulin Therapies

  • If changing patients from another insulin glargine product, 100 units/mL, to BASAGLAR, the dose of BASAGLAR should be the same as the other insulin glargine product, 100 units/mL.
  • If changing patients from a once-daily insulin glargine product, 300 units/mL, to once-daily BASAGLAR, the recommended initial BASAGLAR dosage is 80% of the insulin glargine product, 300 units/mL
    [see Warnings and Precautions ]
    .
  • If changing from a treatment regimen with an intermediate- or long-acting insulin to a regimen with BASAGLAR, a change in the dose of the basal insulin may be required.
  • If changing patients from twice-daily NPH insulin to once-daily BASAGLAR, the recommended initial BASAGLAR dosage is 80% of the total daily NPH dosage
    [see Warnings and Precautions ]
    .
  )
• Administer subcutaneously once daily at any time of day, but at the same time every day. (
  2.2 General Dosing Instructions

  • In patients with type 1 diabetes, BASAGLAR must be used concomitantly with short-acting insulin.
  • Inject BASAGLAR subcutaneously once daily at any time of day but at the same time every day.
  • Individualize and adjust the dosage of BASAGLAR based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
  • Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), during acute illness, or changes in renal or hepatic function. Dosage adjustments should only be made under medical supervision with appropriate glucose monitoring
    [see Warnings and Precautions ]
    .
  • The BASAGLAR prefilled pens each dials in 1 unit increments and delivers a maximum dose of 80 units per injection.
  )
• Rotate injection sites into the abdominal area, thigh, or deltoid to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. (
  2.1 Important Administration Instructions

  • Always check insulin labels before administration
    [see Warnings and Precautions ]
    .
  • Visually inspect BASAGLAR prefilled pens for particulate matter and discoloration prior to administration. Only use if the solution is clear and colorless with no visible particles.
  • Administer BASAGLAR subcutaneously into the abdominal area, thigh, or deltoid, and rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis
    [see Warnings and Precautions and Adverse Reactions ]
    .
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ]
    .
  • Use BASAGLAR with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • Do not dilute or mix BASAGLAR with any other insulin or solution.
  • Do not administer intravenously or via an insulin pump.
  )
• Closely monitor glucose when converting to BASAGLAR and during initial weeks thereafter. (
  2.2 General Dosing Instructions

  • In patients with type 1 diabetes, BASAGLAR must be used concomitantly with short-acting insulin.
  • Inject BASAGLAR subcutaneously once daily at any time of day but at the same time every day.
  • Individualize and adjust the dosage of BASAGLAR based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
  • Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), during acute illness, or changes in renal or hepatic function. Dosage adjustments should only be made under medical supervision with appropriate glucose monitoring
    [see Warnings and Precautions ]
    .
  • The BASAGLAR prefilled pens each dials in 1 unit increments and delivers a maximum dose of 80 units per injection.
  )
• Do not dilute or mix with any other insulin or solution. (
  2.1 Important Administration Instructions

  • Always check insulin labels before administration
    [see Warnings and Precautions ]
    .
  • Visually inspect BASAGLAR prefilled pens for particulate matter and discoloration prior to administration. Only use if the solution is clear and colorless with no visible particles.
  • Administer BASAGLAR subcutaneously into the abdominal area, thigh, or deltoid, and rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis
    [see Warnings and Precautions and Adverse Reactions ]
    .
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ]
    .
  • Use BASAGLAR with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • Do not dilute or mix BASAGLAR with any other insulin or solution.
  • Do not administer intravenously or via an insulin pump.
  )

Injection: 100 units/mL (U-100) clear and colorless solution available as:

• 3 mL single-patient-use BASAGLAR KwikPen
• 3 mL single-patient-use BASAGLAR Tempo Pen

Published studies with use of insulin glargine products during pregnancy have not reported a clear

association with insulin glargine products and adverse developmental outcomes

The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20-25% in women with a HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

• Never share
  a BASAGLAR prefilled pen between patients, even if the needle is changed. (
  5.1 Never Share a BASAGLAR Prefilled Pen Between Patients

  BASAGLAR prefilled pens must never be shared between patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens.
  )
• Hyperglycemia or hypoglycemia with changes in insulin regimen:
  Make changes to a patient's insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. (
  5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen

  Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia

  [see Warnings and Precautions ]

  or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia

  [see Adverse Reactions ]

  .

  Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.
  )
• Hypoglycemia:
  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. (
  5.3 Hypoglycemia

  Hypoglycemia is the most common adverse reaction associated with insulins, including BASAGLAR

  [see Adverse Reactions ]

  . Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). BASAGLAR, or any insulin, should not be used during episodes of hypoglycemia

  [see Contraindications ]

  .

  Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers)

  [see Drug Interactions ]

  , or in patients who experience recurrent hypoglycemia.

  Risk Factors for Hypoglycemia

  The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of BASAGLAR may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature

  [see Clinical Pharmacology ]

  . The risk of hypoglycemia generally increases with intensity of glycemic control. Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to co-administered medication

  [see Drug Interactions ]

  . Patients with renal or hepatic impairment may be at higher risk of hypoglycemia

  [see Use in Specific Populations ]

  .

  Risk Mitigation Strategies for Hypoglycemia

  Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended.

  The long-acting effect of BASAGLAR may delay recovery from hypoglycemia.
  ,
  6.1 Clinical Trial Experience

  Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

  Two clinical trials with BASAGLAR were conducted: one in type 1 diabetes and one in type 2 diabetes.

  The type 1 diabetes population had the following characteristics: Mean age was 41 years and mean duration of diabetes was 16 years. 58% were male. 75% were Caucasian, 2% Black or African American and 4% American Indian or Alaskan native. 4% were Hispanic. At baseline, mean eGFR was 109 mL/min/1.73m². 73.5 percent of patients had eGFR>90 mL/min/1.73m². The mean BMI was approximately 26 kg/m². HbA_1cat baseline was 7.8%. The data in Table 1reflect exposure of 268 patients to BASAGLAR with a mean exposure duration of 49 weeks.

  The type 2 diabetes population had the following characteristics: Mean age was 59 years and mean duration of diabetes was 11 years. 50% were male. 78% were Caucasian, 8% Black or African American and 5% American Indian or Alaskan native. 28% were Hispanic. At baseline, mean eGFR was 109 mL/min/1.73m². 67.5 percent of patients had eGFR>90 mL/min/1.73m². The mean BMI was approximately 32 kg/m². HbA_1cat baseline was 8.3%. The data in Table 2reflect exposure of 376 patients to BASAGLAR with a mean exposure duration of 22 weeks.

  Common adverse reactions were defined as reactions occurring in ≥5% of the population studied. Common adverse reactions during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus (other than hypoglycemia) are listed in Table 1and Table 2, respectively.

  Table 1: Adverse reactions occurring in ≥5% of adult patients with type 1 diabetes treated with BASAGLAR in a 52-week trial

  aInfections other than nasopharyngitis or upper respiratory tract infection.
  	BASAGLAR + Insulin Lispro, % (n=268)
  Infectiona	24
  Nasopharyngitis	16
  Upper respiratory tract infection	8

  Table 2: Adverse reactions occurring in ≥5% of adult patients with type 2 diabetes treated with BASAGLAR in a 24-week trial

  aInfections other than nasopharyngitis or upper respiratory tract infection.
  	BASAGLAR + Oral Antidiabetic Medication, % (n=376)
  Infectiona	17
  Nasopharyngitis	6
  Upper respiratory tract infection	5

  The frequencies of adverse reactions during a clinical trial of 5 years duration with another insulin glargine product, 100 units/mL, in patients with type 2 diabetes mellitus are listed in Table 3.

  Table 3: Common adverse reactions in 5-year trial of adult patients with type 2 diabetes (adverse reactions with incidence ≥10% and higher with another insulin glargine product, 100 units/mL, than comparator)

  	Another Insulin Glargine Product, % (n=514)	NPH, % (n=503)
  Hypertension	20	19
  Sinusitis	19	18
  Cataract	18	16
  Bronchitis	15	14
  Back pain	13	12
  Cough	12	7
  Urinary tract infection	11	10
  Diarrhea	11	10
  Depression	11	10
  Headache	10	9

  The frequencies of adverse reactions during clinical trials with another insulin glargine product, 100 units/mL, in children and adolescents with type 1 diabetes mellitus are listed in Table 4.

  Table 4: Adverse reactions in a 28-week clinical trial of pediatric patients with type 1 diabetes (adverse reactions with frequency ≥5% and the same or higher with another insulin glargine product, 100 units/mL, than comparator)

  	Another Insulin Glargine Product, % (n=174)	NPH, % (n=175)
  Rhinitis	5	5

  Severe Hypoglycemia

  Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including BASAGLAR. The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for BASAGLAR with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice.

  Severe symptomatic hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose below 50 mg/dL (≤56 mg/dL in the 5-year trial and ≤36 mg/dL in the ORIGIN trial) or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration.

  The incidence of severe symptomatic hypoglycemia in patients receiving BASAGLAR with type 1 diabetes mellitus and type 2 diabetes mellitus

  [see Clinical Studies ]

  was 4% at 52 weeks and 1% at 24 weeks, respectively.

  The incidence of severe symptomatic hypoglycemia in a clinical trial with another insulin glargine product, 100 units/mL, in children and adolescents age 6 to 15 years with type 1 diabetes

  [see Clinical Studies ]

  was 23% at 26 weeks.

  Table 5displays the proportion of patients experiencing severe symptomatic hypoglycemia in another insulin glargine product, 100 units/mL, and Standard Care groups in the ORIGIN Trial

  [see Clinical Studies ]

  .

  Table 5: Severe Symptomatic Hypoglycemia in the ORIGIN Trial

  	ORIGIN Trial Median duration of follow-up: 6.2 years
  	Another Insulin Glargine Product, 100 units/mL (N=6231)	Standard Care (N=6273)
  Percent of patients	6	2

  Allergic Reactions

  Some patients taking insulins, including BASAGLAR have experienced erythema, local edema, and pruritus at the site of injection. These conditions were usually self-limiting. Severe cases of generalized allergy (anaphylaxis) have been reported.

  Peripheral Edema

  Some patients taking BASAGLAR have experienced sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

  Lipodystrophy

  Administration of insulins subcutaneously, including BASAGLAR, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients

  [see Dosage and Administration ]

  .

  Weight gain

  Weight gain has occurred with insulins, including BASAGLAR, and has been attributed to the anabolic effects of insulin and the decrease in glycosuria.
  )
• Hypoglycemia due to medication errors:
  Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. (
  5.4 Hypoglycemia Due to Medication Errors

  Accidental mix-ups between insulin products have been reported. To avoid medication errors between BASAGLAR and other insulins, instruct patients to always check the insulin label before each injection.
  )
• Hypersensitivity reactions:
  Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue BASAGLAR, monitor and treat if indicated. (
  5.5 Hypersensitivity Reactions

  Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including BASAGLAR. If hypersensitivity reactions occur, discontinue BASAGLAR; treat per standard of care and monitor until symptoms and signs resolve

  [see Adverse Reactions ]

  . BASAGLAR is contraindicated in patients who have had hypersensitivity reactions to insulin glargine or one of the excipients

  [see Contraindications ]

  .
  ,
  6.1 Clinical Trial Experience

  Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

  Two clinical trials with BASAGLAR were conducted: one in type 1 diabetes and one in type 2 diabetes.

  The type 1 diabetes population had the following characteristics: Mean age was 41 years and mean duration of diabetes was 16 years. 58% were male. 75% were Caucasian, 2% Black or African American and 4% American Indian or Alaskan native. 4% were Hispanic. At baseline, mean eGFR was 109 mL/min/1.73m². 73.5 percent of patients had eGFR>90 mL/min/1.73m². The mean BMI was approximately 26 kg/m². HbA_1cat baseline was 7.8%. The data in Table 1reflect exposure of 268 patients to BASAGLAR with a mean exposure duration of 49 weeks.

  The type 2 diabetes population had the following characteristics: Mean age was 59 years and mean duration of diabetes was 11 years. 50% were male. 78% were Caucasian, 8% Black or African American and 5% American Indian or Alaskan native. 28% were Hispanic. At baseline, mean eGFR was 109 mL/min/1.73m². 67.5 percent of patients had eGFR>90 mL/min/1.73m². The mean BMI was approximately 32 kg/m². HbA_1cat baseline was 8.3%. The data in Table 2reflect exposure of 376 patients to BASAGLAR with a mean exposure duration of 22 weeks.

  Common adverse reactions were defined as reactions occurring in ≥5% of the population studied. Common adverse reactions during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus (other than hypoglycemia) are listed in Table 1and Table 2, respectively.

  Table 1: Adverse reactions occurring in ≥5% of adult patients with type 1 diabetes treated with BASAGLAR in a 52-week trial

  aInfections other than nasopharyngitis or upper respiratory tract infection.
  	BASAGLAR + Insulin Lispro, % (n=268)
  Infectiona	24
  Nasopharyngitis	16
  Upper respiratory tract infection	8

  Table 2: Adverse reactions occurring in ≥5% of adult patients with type 2 diabetes treated with BASAGLAR in a 24-week trial

  aInfections other than nasopharyngitis or upper respiratory tract infection.
  	BASAGLAR + Oral Antidiabetic Medication, % (n=376)
  Infectiona	17
  Nasopharyngitis	6
  Upper respiratory tract infection	5

  The frequencies of adverse reactions during a clinical trial of 5 years duration with another insulin glargine product, 100 units/mL, in patients with type 2 diabetes mellitus are listed in Table 3.

  Table 3: Common adverse reactions in 5-year trial of adult patients with type 2 diabetes (adverse reactions with incidence ≥10% and higher with another insulin glargine product, 100 units/mL, than comparator)

  	Another Insulin Glargine Product, % (n=514)	NPH, % (n=503)
  Hypertension	20	19
  Sinusitis	19	18
  Cataract	18	16
  Bronchitis	15	14
  Back pain	13	12
  Cough	12	7
  Urinary tract infection	11	10
  Diarrhea	11	10
  Depression	11	10
  Headache	10	9

  The frequencies of adverse reactions during clinical trials with another insulin glargine product, 100 units/mL, in children and adolescents with type 1 diabetes mellitus are listed in Table 4.

  Table 4: Adverse reactions in a 28-week clinical trial of pediatric patients with type 1 diabetes (adverse reactions with frequency ≥5% and the same or higher with another insulin glargine product, 100 units/mL, than comparator)

  	Another Insulin Glargine Product, % (n=174)	NPH, % (n=175)
  Rhinitis	5	5

  Severe Hypoglycemia

  Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including BASAGLAR. The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for BASAGLAR with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice.

  Severe symptomatic hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose below 50 mg/dL (≤56 mg/dL in the 5-year trial and ≤36 mg/dL in the ORIGIN trial) or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration.

  The incidence of severe symptomatic hypoglycemia in patients receiving BASAGLAR with type 1 diabetes mellitus and type 2 diabetes mellitus

  [see Clinical Studies ]

  was 4% at 52 weeks and 1% at 24 weeks, respectively.

  The incidence of severe symptomatic hypoglycemia in a clinical trial with another insulin glargine product, 100 units/mL, in children and adolescents age 6 to 15 years with type 1 diabetes

  [see Clinical Studies ]

  was 23% at 26 weeks.

  Table 5displays the proportion of patients experiencing severe symptomatic hypoglycemia in another insulin glargine product, 100 units/mL, and Standard Care groups in the ORIGIN Trial

  [see Clinical Studies ]

  .

  Table 5: Severe Symptomatic Hypoglycemia in the ORIGIN Trial

  	ORIGIN Trial Median duration of follow-up: 6.2 years
  	Another Insulin Glargine Product, 100 units/mL (N=6231)	Standard Care (N=6273)
  Percent of patients	6	2

  Allergic Reactions

  Some patients taking insulins, including BASAGLAR have experienced erythema, local edema, and pruritus at the site of injection. These conditions were usually self-limiting. Severe cases of generalized allergy (anaphylaxis) have been reported.

  Peripheral Edema

  Some patients taking BASAGLAR have experienced sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

  Lipodystrophy

  Administration of insulins subcutaneously, including BASAGLAR, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients

  [see Dosage and Administration ]

  .

  Weight gain

  Weight gain has occurred with insulins, including BASAGLAR, and has been attributed to the anabolic effects of insulin and the decrease in glycosuria.
  )
• Hypokalemia:
  May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. (
  5.6 Hypokalemia

  All insulins, including BASAGLAR, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).
  )
• Fluid retention and heart failure with concomitant use of thiazolidinediones (TZDs):
  Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs. (
  5.7 Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists

  Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including BASAGLAR, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.
  )