Type 2 diabetes comparable A1C reduction

BASAGLAR demonstrated noninferiority to Lantus® (insulin glargine injection) products (approved in the US or outside the US) as measured by A1C reduction in adult patients with type 2 diabetes1,4

Type 2 diabetes: change in A1C from baseline at 24 weeks

Type 2 diabetes: change in A1C from baseline at 24 weeks

Difference of 0.052% (95% CI -0.070 to 0.175)
Noninferiority margin 0.4% and then 0.3%

*Three patients randomized to BASAGLAR did not receive study drug and were not included in the full analysis set. Observed A1C data at 24 weeks were available from 331 (88%) and 329 (87%) patients randomized to the BASAGLAR and Lantus products (approved in the US or outside the US) groups, respectively.

Approved in the US or outside the US.

CI=confidence interval; OAMs=oral anti-diabetic medications.

SELECT SAFETY INFORMATION
ADVERSE REACTIONS
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. 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.

A comparable percentage of adult patients with type 2 diabetes achieved A1C <7% at 24 weeks1,4*

BASAGLAR + OAMs (n=376†; baseline A1C: 8.35%) 48.8%

BASAGLAR + OAMs
(n=376; baseline A1C: 8.35%)

Lantus products† + OAMs (n=380†; baseline A1C: 8.31%) 52.5%

Lantus products + OAMs
(n=380; baseline A1C: 8.31%)

*Secondary endpoint.

Full analysis set; n values reflect maximum sample size.

Approved in the US or outside the US.

OAMs=oral anti-diabetic medications.


Trial design: 24-week phase 3, randomized, double-blind trial of 756 adult patients with type 2 diabetes who were either insulin-naive and failed to achieve adequate glycemic control on at least 2 OAMs, or were already on Lantus products (approved in the US or outside the US) along with 2 or more OAMs with adequate or inadequate glycemic control. The primary endpoint was noninferiority of BASAGLAR to Lantus products (approved in the US or outside the US) as measured by change in A1C from baseline at 24 weeks.1,4

The starting dose for all insulin-naive patients was 10 units/day, while patients entering the study on Lantus products (approved in the US or outside the US) were randomized to either BASAGLAR or Lantus products (approved in the US or outside the US) at a dose equivalent to their prestudy Lantus products (approved in the US or outside the US) dose. BASAGLAR and Lantus products (approved in the US or outside the US) titrations were patient-driven based on self-measured fasting plasma glucose with a target of ≤100 mg/dL.4

SELECT SAFETY INFORMATION
ADVERSE REACTIONS
Adverse reactions commonly associated with insulin glargine products (5% or greater incidence) are: hypoglycemia, allergic reactions, injection site reaction, lipodystrophy, pruritus, rash, edema, and weight gain.
DRUG INTERACTIONS
Certain drugs may affect glucose metabolism, requiring insulin dose adjustment and close monitoring of blood glucose. The signs and symptoms of hypoglycemia may be blunted when beta-blockers, clonidine, guanethidine, and reserpine are co-administered with BASAGLAR.

Type 2 diabetes adverse events

This trial was not designed to evaluate the relative safety between BASAGLAR and Lantus products (approved in the US or outside the US), and comparator adverse event rates are not an adequate basis for comparison of rates between the products.

BASAGLAR vs Lantus products (approved in the US or outside the US): severe symptomatic hypoglycemia over 24 weeks of treatment4

BASAGLAR + OAMs (n=376*) <1%

BASAGLAR + OAMs
(n=376*)

Lantus products† + OAMs (n=380*) <1%

Lantus products + OAMs
(n=380*)

*Full analysis set; n values reflect maximum sample size.

Approved in the US or outside the US.

Hypoglycemia was the most commonly observed adverse reaction in patients using insulin, including BASAGLAR. Hypoglycemia was defined as blood glucose ≤3.9 mmol/L (≤70 mg/dL) or a sign or symptom associated with hypoglycemia. Severe symptomatic hypoglycemia was defined as an event with symptoms consistent with hypoglycemia that required assistance of another person, and was associated with either blood glucose levels below 50 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration.1,4

Rates of reported hypoglycemia depend upon the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic 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 may not be representative of hypoglycemia rates that will occur in clinical practice.

Type 2 diabetes: adverse reactions occurring in ≥5% of adult patients treated with BASAGLAR® (insulin glargine injection) 100 units/mL or Lantus products* over 24 weeks of treatment1,5

*Approved in the US or outside the US.

Infections other than nasopharyngitis or upper respiratory tract infection.

Infections were a category of treatment-emergent adverse events that were reported during the 24-week trial and included events such as influenza, urinary tract infection, bronchitis, gastroenteritis, and sinusitis. Excluded were nasopharyngitis and upper respiratory tract infection.6

OAMS=oral anti-diabetic medications.

Type 1 diabetes comparable A1C reduction

BASAGLAR demonstrated noninferiority to Lantus products (approved in the US or outside the US) as measured by A1C reduction in adult patients with type 1 diabetes1,7

Type 1 diabetes: change in A1C from baseline at 24 weeks

Type 1 diabetes: change in A1C from baseline at 24 weeks

Difference of 0.108% (95% CI -0.002 to 0.219)
Noninferiority margin 0.4% and then 0.3%

*One patient randomized to the BASAGLAR group was not included in the full analysis set. Observed A1C data at 24 weeks were available from 256 (96%) and 258 (97%) patients randomized to the BASAGLAR and Lantus products (approved in the US or outside the US) groups, respectively.

Approved in the US or outside the US.

CI=confidence interval.

SELECT SAFETY INFORMATION
CONTRAINDICATIONS
BASAGLAR is contraindicated during episodes of hypoglycemia, and in patients with hypersensitivity to insulin glargine or one of its excipients.
WARNINGS AND PRECAUTIONS
BASAGLAR KwikPen® must never be shared between patients, even if the needle is changed. Sharing poses a risk of transmission of blood borne pathogens.

A comparable percentage of adult patients with type 1 diabetes achieved A1C <7% at 24 weeks1,7*

BASAGLAR + Insulin lispro (n=268†; baseline A1C: 7.75%) 34.5%

BASAGLAR + Insulin lispro
(n=268; baseline A1C: 7.75%)

Lantus productst + Insulin lispro (n=267†; baseline A1C: 7.79%) 32.2%

Lantus products + Insulin lispro
(n=267; baseline A1C: 7.79%)

*Secondary endpoint.

Full analysis set; n values reflect maximum sample size.

Approved in the US or outside the US.


Trial design: 52-week phase 3, randomized, open-label study of 535 adult patients with type 1 diabetes who were also treated with insulin lispro. The primary endpoint was noninferiority of BASAGLAR to Lantus products (approved in the US or outside the US) as measured by change in A1C from baseline at 24 weeks.1,7

Patients started on the same dose of BASAGLAR or Lantus products (approved in the US or outside the US) and at the same time of day as their prestudy basal insulin; mealtime insulin was replaced with insulin lispro at doses equivalent to prestudy mealtime insulin; titrations were investigator-driven based on self-measured fasting plasma glucose to achieve glycemic targets (A1C <7%, fasting plasma-equivalent glucose ≤108 mg/dL, and other preprandial capillary blood glucoses [70 to 130 mg/dL]).7

SELECT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. These changes should be made cautiously and only under close medical supervision, and the frequency of blood glucose monitoring should be increased. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.
Hypoglycemia is the most common adverse reaction associated with insulins, including BASAGLAR. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death.

Type 1 diabetes adverse events

This trial was not designed to evaluate the relative safety between BASAGLAR and Lantus products (approved in the US or outside the US), and comparator adverse event rates are not an adequate basis for comparison of rates between the products.

BASAGLAR vs Lantus products (approved in the US or outside the US): severe symptomatic hypoglycemia over 52 weeks of treatment7

BASAGLAR + Insulin lispro 4%

BASAGLAR + Insulin lispro
(n=268*)

Lantus products† + OAMs (n=380*) 4%

Lantus products + Insulin lispro
(n=267*)

*Full analysis set; n values reflect maximum sample size.

Approved in the US or outside the US.

Hypoglycemia was the most commonly observed adverse reaction in patients using insulin, including BASAGLAR. Hypoglycemia was defined as blood glucose ≤3.9 mmol/L (≤70 mg/dL) or a sign or symptom associated with hypoglycemia. Severe symptomatic hypoglycemia was defined as an event with symptoms consistent with hypoglycemia that required assistance of another person, and was associated with either blood glucose levels below 50 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration.1,7

Rates of reported hypoglycemia depend upon the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic 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 may not be representative of hypoglycemia rates that will occur in clinical practice.

Type 1 diabetes: adverse reactions occurring in ≥5% of adult patients over 52 weeks1,8

*Approved in the US or outside the US.

Infections other than nasopharyngitis or upper respiratory tract infection.

Infections were a category of treatment-emergent adverse events that were reported during the 52-week trial and included events such as influenza, urinary tract infection, bronchitis, gastroenteritis, and sinusitis. Excluded were nasopharyngitis and upper respiratory tract infection.9

Indications and Important Safety Information
Indication

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.

LIMITATION OF USE

BASAGLAR is not recommended for the treatment of diabetic ketoacidosis.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS

BASAGLAR is contraindicated during episodes of hypoglycemia, and in patients with hypersensitivity to insulin glargine or one of its excipients.

WARNINGS AND PRECAUTIONS

BASAGLAR KwikPen® must never be shared between patients, even if the needle is changed. Sharing poses a risk of transmission of blood borne pathogens.

Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. These changes should be made cautiously and only under close medical supervision, and the frequency of blood glucose monitoring should be increased. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.

Hypoglycemia is the most common adverse reaction associated with insulins, including BASAGLAR. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death.

Accidental mix-ups between another insulin glargine product (100 units/mL) and other insulins, particularly rapid-acting insulins, have been reported. To avoid medication errors between BASAGLAR and other insulins, instruct patients to always check the insulin label before each injection.

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including BASAGLAR. If hypersensitivity reactions occur, discontinue BASAGLAR; treat per standard of care and monitor until symptoms and signs resolve. BASAGLAR is contraindicated in patients who have had hypersensitivity reactions to insulin glargine or one of the excipients.

All insulin products, 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.

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. 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.

ADVERSE REACTIONS

Adverse reactions commonly associated with insulin glargine products (5% or greater incidence) are: hypoglycemia, allergic reactions, injection site reaction, lipodystrophy, pruritus, rash, edema, and weight gain.

DRUG INTERACTIONS

Certain drugs may affect glucose metabolism, requiring insulin dose adjustment and close monitoring of blood glucose. The signs and symptoms of hypoglycemia may be blunted when beta-blockers, clonidine, guanethidine, and reserpine are co-administered with BASAGLAR.

BV HCP ISI 24JUN2016

For more information, please see Full Prescribing Information, including Patient Information and Instructions for Use.

BASAGLAR and KwikPen® are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates and are available by prescription only.

References
1. BASAGLAR [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company. 2. Lantus [Prescribing Information]. Bridgewater, NJ: sanofi-aventis U.S. LLC; 2015. 3. Linnebjerg H, Lam EC, Seger ME, et al. Diabetes Care. 2015;38:2226-2233. 4. Rosenstock J, Hollander P, Bhargava A, et al. Diabetes Obes Metab. 2015;17:734-741. 5. Data on file, Lilly USA, LLC. BAS20160408A. 6. Data on file, Lilly USA, LLC. BAS20160811B. 7. Blevins TC, Dahl D, Rosenstock J, et al. Diabetes Obes Metab. 2015;17:726-733. 8. Data on file, Lilly USA, LLC. BAS20151103E. 9. Data on file, Lilly USA, LLC. BAS20160811A. 10. Gerstein HC, Yale JF, Harris SB, et al. Diabet Med. 2006;23:736-742. 11. BASAGLAR KwikPen [Instructions for Use]. Indianapolis, IN: Eli Lilly and Company.