DailyMed Label: Insulin Glargine Solostar

DailyMed Label: Insulin Glargine

2024

DailyMed Prescription

Insulin Glargine

insulin Glargine-yfgn

Biocon Biologics Inc.

NDC: 83257-015

NDC: 83257-015

NDC: 83257-014

NDC: 83257-014

Insulin glargine-yfgn is a long-acting human insulin analog produced by recombinant DNA technology utilizing a recombinant yeast strain, Pichia pastoris. Insulin glargine-yfgn differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Insulin glargine-yfgn has a molecular weight of 6063 Da. Insulin Glargine-yfgn is a sterile, clear and colorless solution for subcutaneous use in a 10 mL multiple-dose vial and a 3 mL single-patient-use prefilled pen. Prefilled Pen and Vial: Each mL contains 100 units of insulin glargine-yfgn and the inactive ingredients: glycerol (20 mg), metacresol (2.7 mg), zinc chloride (content adjusted to provide 30 mcg zinc ion), and Water for Injection, USP. The vial also contains polysorbate 20 (20 mcg). The pH is adjusted by addition of aqueous solutions of hydrochloric acid and/or sodium hydroxide. Insulin glargine - yfgn has a pH of approximately 4.

Insulin Glargine-yfgn is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. Limitations of Use Insulin Glargine-yfgn is not recommended for the treatment of diabetic ketoacidosis. Insulin Glargine-yfgn is a long-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. ( 1 ) Limitations of Use Not recommended for the treatment of diabetic ketoacidosis. ( 1 )

• Individualize dosage based on metabolic needs, blood glucose monitoring, glycemic control, type of diabetes, and prior insulin use. ( 2.2 ) • Administer subcutaneously into the abdominal area, thigh, or deltoid once daily at any time of day, but at the same time every day. ( 2.1 ) • Do not dilute or mix with any other insulin or solution. ( 2.1 ) • Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. ( 2.1 ) • See Full Prescribing Information for the recommended starting dosage in patients with type 2 diabetes (2.3) and how to change to Insulin Glargine-yfgn from other insulins. ( 2.4 ) • Closely monitor glucose when switching to Insulin Glargine-yfgn and during initial weeks thereafter. ( 2.4 ) • Always check insulin labels before administration. This product is SEMGLEE (insulin glargine-yfgn) [see Warnings and Precautions (5.4) ]. • Visually inspect Insulin Glargine-yfgn vials and prefilled pens for particulate matter and discoloration prior to administration. Only use if the solution is clear and colorless with no visible particles. • Administer Insulin Glargine-yfgn 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 (5.2) and Adverse Reactions (6) ] . • During changes to a patient’s insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2) ] . • Do not administer intravenously or via an insulin pump. • Do not dilute or mix Insulin Glargine-yfgn with any other insulin or solution. • The Insulin Glargine-yfgn prefilled pen dials in 1-unit increments. • Use the Insulin Glargine-yfgn prefilled pen with caution in patients with visual impairment who may rely on audible clicks to dial their dose. • Administer Insulin Glargine-yfgn subcutaneously once daily at any time of day but at the same time every day. • Individualize and adjust the dosage of Insulin Glargine-yfgn based on the patient’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 (5.2) ] . • In patients with type 1 diabetes, Insulin Glargine-yfgn must be used concomitantly with short-acting insulin. Recommended Starting Dosage in Patients with Type 1 Diabetes The recommended starting dosage of Insulin Glargine-yfgn in patients with type 1 diabetes is approximately one-third of the total daily insulin requirements. Use short-acting, premeal insulin to satisfy the remainder of the daily insulin requirements. Recommended Starting Dosage in Patients with Type 2 Diabetes The recommended starting dosage of Insulin Glargine-yfgn in patients with type 2 diabetes who are not currently treated with insulin is 0.2 units/kg or up to 10 units once daily. Dosage adjustments are recommended to lower the risk of hypoglycemia when switching patients to Insulin Glargine-yfgn from other insulin therapies [see Warnings and Precautions (5.3) ] . When switching from: • Once-daily insulin glargine 300 units/mL to once-daily Insulin Glargine-yfgn (100 units/mL), the recommended starting Insulin Glargine-yfgn dosage is 80% of the insulin glargine, 300 units/mL dosage that is being discontinued. • Once-daily NPH insulin to once-daily Insulin Glargine-yfgn, the recommended starting Insulin Glargine-yfgn dosage is the same as the dosage of NPH that is being discontinued. • Twice-daily NPH insulin to once-daily insulin Glargine-yfgn, the recommended starting insulin Glargine-yfgn dosage is 80% of the total NPH dosage that is being discontinued.

Injection: 100 units/mL (U-100) a clear and colorless solution available as: • 10 mL multiple dose vial • 3 mL single-patient-use prefilled pen Injection: 100 units/mL (U-100) available as: • 10 mL multiple-dose vial ( 3 ) • 3 mL single-patient-use prefilled pen ( 3 )

Insulin Glargine-yfgn is contraindicated: • During episodes of hypoglycemia [see Warnings and Precautions (5.3) ] • In patients with hypersensitivity to insulin glargine products or any of the excipients in Insulin Glargine-yfgn [see Warnings and Precautions (5.5) ] • During episodes of hypoglycemia ( 4 ) • Hypersensitivity to insulin glargine products or any excipient in Insulin Glargine-yfgn ( 4 )

• Never share an Insulin Glargine-yfgn prefilled pen, insulin syringe, or needle between patients, even if the needle is changed. ( 5.1 ) • 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 ) • Hypoglycemia: May be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, concomitant drugs, meal pattern, physical activity; and in patients with renal or hepatic impairment and hypoglycemia unawareness. ( 5.3 ) • Hypoglycemia due to medication errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. ( 5.4 ) • Hypersensitivity reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue Insulin Glargine-yfgn. Monitor and treat if indicated. ( 5.5 ) • Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. ( 5.6 ) • Fluid retention and heart failure with concomitant use of thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation of TZD if heart failure occurs. ( 5.7 ) Insulin Glargine-yfgn prefilled pens must never be shared between patients, even if the needle is changed. Patients using Insulin Glargine-yfgn vials must never re-use or share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. 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 (5.3) ] 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 unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions (6) ] . 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 oral and antidiabetic products may be needed. Hypoglycemia is the most common adverse reaction associated with insulins, including insulin glargine products. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly, and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, using drugs that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7) ] , or who experience recurrent hypoglycemia. The long-acting effect of insulin glargine products may delay recovery from 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 insulin glargine products may vary in different patients or at different times in the same patient and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [see Clinical Pharmacology (12.2) ] . 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 concomitant drugs [see Drug Interactions (7) ] . Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.6 , 8.7) ] . 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. Accidental mix-ups among insulin products have been reported. To avoid medication errors between Insulin Glargine-yfgn and other insulins, instruct patients to always check the insulin label before each injection [see Adverse Reactions (6.3) ] . Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including insulin glargine products [see Adverse Reactions (6.1) ] . If hypersensitivity reactions occur, discontinue insulin glargine-yfgn; treat per standard of care and monitor until symptoms and signs resolve. insulin glargine-yfgn is contraindicated in patients who have had hypersensitivity reactions to insulin glargine products or one of the excipients. All insulins, including insulin glargine products, 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). Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including Insulin Glargine-yfgn, 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.

The following adverse reactions are discussed elsewhere:

Table 8 includes clinically significant drug interactions with Insulin Glargine-yfgn. Table 8: Clinically Significant Drug Interactions with Insulin Glargine-yfgn Drugs that May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors. Intervention: Dosage reductions and increased frequency of glucose monitoring may be required when Insulin Glargine-yfgn is coadministered with these drugs. Drugs that May Decrease the Blood Glucose Lowering Effect of Insulin Glargine-yfgn Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Intervention: Dosage increases and increased frequency of glucose monitoring may be required when Insulin Glargine-yfgn is coadministered with these drugs. Drugs that May Increase or Decrease the Blood Glucose Lowering Effect of Insulin Glargine-yfgn Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention: Dosage adjustment and increased frequency of glucose monitoring may be required when Insulin Glargine-yfgn is coadministered with these drugs. Drugs that May Blunt Signs and Symptoms of Hypoglycemia Drugs: Beta-blockers, clonidine, guanethidine, and reserpine. Intervention: Increased frequency of glucose monitoring may be required when Insulin Glargine-yfgn is coadministered with these drugs. • Drugs that Affect Glucose Metabolism : Adjustment of insulin dosage may be needed. ( 7 ) • Antiadrenergic Drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Signs and symptoms of hypoglycemia may be reduced or absent. ( 7 )     * Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of Insulin Glargine -yfgn has been demonstrated for the condition(s) of use (e.g., indication(s), dosing regimen(s)), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information.

Risk Summary Published studies with use of insulin glargine products during pregnancy have not reported a clear association with insulin glargine products and adverse developmental outcomes (see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). Rats and rabbits were exposed to insulin glargine in animal reproduction studies during organogenesis, respectively 50 times and 10 times the human subcutaneous dosage of 0.2 units/kg/day. Overall, the effects of insulin glargine did not generally differ from those observed with regular human insulin (see Data). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The estimated background risk of major birth defects is 6% to 10% in women with pregestational diabetes with a peri-conceptional HbA1c >7 and has been reported to be as high as 20% to 25% in women with a peri-conceptional HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. Clinical Considerations Disease-Associated Maternal and/or Embryo-fetal Risk Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Data Human Data Published data do not report a clear association with insulin glargine products and major birth defects, miscarriage, or adverse maternal or fetal outcomes when insulin glargine is used during pregnancy. However, these studies cannot definitely establish the absence of any risk because of methodological limitations including small sample size and some lacking comparator groups. Animal Data Subcutaneous reproduction and teratology studies have been performed with insulin glargine and regular human insulin in rats and Himalayan rabbits. Insulin glargine was given to female rats before mating, during mating, and throughout pregnancy at doses up to 0.36 mg/kg/day, which is approximately 50 times the recommended human subcutaneous starting dosage of 0.2 units/kg/day (0.007 mg/kg/day), on a mg/kg basis. In rabbits, doses of 0.072 mg/kg/day, which is approximately 10 times the recommended human subcutaneous starting dosage of 0.2 units/kg/day on a mg/kg basis, were administered during organogenesis. The effects of insulin glargine did not generally differ from those observed with regular human insulin in rats or rabbits. However, in rabbits, five fetuses from two litters of the high-dose group exhibited dilation of the cerebral ventricles. Fertility and early embryonic development appeared normal. Risk Summary There are either no or only limited data on the presence of insulin glargine products in human milk, the effects on breastfed infant, or the effects on milk production. Endogenous insulin is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Insulin Glargine-yfgn, and any potential adverse effects on the breastfed child from Insulin Glargine-yfgn or from the underlying maternal condition. The safety and effectiveness of insulin glargine - yfgn to improve glycemic control in pediatric patients with diabetes mellitus have been established. Use of insulin glargine for this indication is supported by Insulin glargine - yfgn’s approval as a biosimilar to insulin glargine and evidence from an adequate and well-controlled study (Study D) in 174 insulin glargine-treated pediatric patients aged 6 to 15 years with type 1 diabetes mellitus, and from adequate and well-controlled studies of insulin glargine in adults with diabetes mellitus  [see Clinical Pharmacology (12.3) , Clinical Studies (14.2) ] . In the pediatric clinical study, pediatric patients with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in studies with type 1 diabetes [see Adverse Reactions (6.1) ] . Of the total number of subjects in controlled clinical studies of patients with type 1 and type 2 diabetes who were treated with insulin glargine, 15% (n = 316) were ≥ 65 years of age and 2% (n = 42) were ≥ 75 years of age. No overall differences in safety or effectiveness of insulin glargine have been observed between patients 65 years of age and older and younger adult patients. Nevertheless, caution should be exercised when Insulin Glargine-yfgn is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dosage increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in geriatric patients. The effect of kidney impairment on the pharmacokinetics of insulin glargine products has not been studied. Some studies with human insulin have shown increased circulating levels of insulin in patients with kidney failure. Frequent glucose monitoring and dosage adjustment may be necessary for Insulin Glargine-yfgn in patients with kidney impairment [see Warnings and Precautions (5.3) ] . The effect of hepatic impairment on the pharmacokinetics of insulin glargine products has not been studied. Frequent glucose monitoring and dosage adjustment may be necessary for Insulin Glargine-yfgn in patients with hepatic impairment [see Warnings and Precautions (5.3) ] .

Insulin Glargine-yfgn (injection) is supplied as a clear and colorless solution containing 100 units/mL (U-100) available as follows: Insulin Glargine-yfgn NDC Number Package Size 10 mL multiple-dose vial 83257-014-11 1 vial per carton 3 mL single-patient-use prefilled pen 83257-015-31 1 pen per carton 83257-015-32 5 pens per carton   Additional Information about Insulin Glargine-yfgn: • The Insulin Glargine-yfgn prefilled pen dials in 1-unit increments. • Needles are not included in the packs. BD ® Ultra-Fine needles are compatible with this pen. Dispense in the original sealed carton with the enclosed Instructions for Use. Store unused Insulin Glargine-yfgn in a refrigerator between 2° to 8°C (36° to 46°F). Do not freeze. Discard Insulin Glargine-yfgn if it has been frozen. Protect Insulin Glargine-yfgn from direct heat and light. Storage conditions are summarized in the following table: Not in-use (unopened) Refrigerated (2° to 8°C [36° to 46°F]) Not in-use (unopened) Room Temperature (up to 30°C [86°F]) In-use (opened) (see temperature below) 10 mL multiple-dose vial Until expiration date 28 days 28 days Refrigerated or room temperature 3 mL single-patient-use prefilled pen Until expiration date 28 days 28 days Room temperature only (Do not refrigerate)

The primary activity of insulin, including insulin glargine products, is regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis. In clinical studies, the glucose-lowering effect on a molar basis (i.e., when given at the same doses) of intravenous insulin glargine is approximately the same as that for human insulin. Figure 1 shows results from a study in patients with type 1 diabetes conducted for a maximum of 24 hours after subcutaneous injection of insulin glargine or NPH insulin. The median time between subcutaneous injection and the end of pharmacological effect was 14.5 hours (range: 9.5 to 19.3 hours) for NPH insulin, and 24 hours (range: 10.8 to > 24 hours) (24 hours was the end of the observation period) for insulin glargine. Figure 1: Glucose-Lowering Effect Over 24 Hours in Patients with Type 1 Diabetes * Determined as amount of glucose infused to maintain constant plasma glucose levels The duration of action after abdominal, deltoid, or thigh subcutaneous administration of insulin glargine was similar. The time course of action of insulins, including insulin glargine products, may vary between patients and within the same patient. Glucose-Lowering Effect Over 24 Hours in Patients with Type 1 Diabetes Absorption After subcutaneous injection of insulin glargine in healthy subjects and in patients with diabetes, the insulin serum concentrations indicated a slower, more prolonged absorption and a relatively constant concentration/time profile over 24 hours with no pronounced peak in comparison to NPH insulin. Elimination Metabolism A metabolism study in humans indicates that insulin glargine is partly metabolized at the carboxyl terminus of the B chain in the subcutaneous depot to form two active metabolites with in vitro activity similar to that of human insulin, M1 (21 A -Gly-insulin) and M2 (21 A -Gly-des- 30 B -Thr-insulin). Unchanged drug and these degradation products are also present in the circulation. Specific Populations Age, Race, Body Mass Index, and Gender Effect of age, race, body mass index (BMI), and gender on the pharmacokinetics of insulin glargine products has not been evaluated. However, in controlled clinical studies in adults (n = 3,890) and a controlled clinical study in pediatric patients (n = 349), subgroup analyses based on age, race, BMI, and gender did not show differences in safety and efficacy between insulin glargine and NPH insulin [see Clinical Studies (14) ] .

In mice and rats, standard two-year carcinogenicity studies with insulin glargine were performed at doses up to 0.455 mg/kg, which was for the rat approximately 65 times the recommended human subcutaneous starting dosage of 0.2 units/kg/day (0.007 mg/kg/day) on a mg/kg basis. Histiocytomas were found at injection sites in male rats and mice in acid vehicle containing groups and are considered a response to chronic tissue irritation and inflammation in rodents. These tumors were not found in female animals, in saline control, or insulin comparator groups using a different vehicle. Insulin glargine was not mutagenic in tests for detection of gene mutations in bacteria and mammalian cells (Ames and HGPRT-test) and in tests for detection of chromosomal aberrations (cytogenetics in vitro in V79 cells and in vivo in Chinese hamsters). In a combined fertility and prenatal and postnatal study in male and female rats at subcutaneous doses up to 0.36 mg/kg/day, which was approximately 50 times the recommended human subcutaneous starting dosage of 0.2 units/kg/day (0.007 mg/kg/day) maternal toxicity due to dose-dependent hypoglycemia, including some deaths, was observed. Consequently, a reduction of the rearing rate occurred in the high-dose group only. Similar effects were observed with NPH insulin.

The safety and effectiveness of insulin glargine given once-daily at bedtime was compared to that of once-daily and twice-daily NPH insulin in open-label, randomized, active-controlled, parallel studies of 2,327 adult patients and 349 pediatric patients with type 1 diabetes mellitus and 1,563 adult patients with type 2 diabetes mellitus (see Tables 9-11). In general, the reduction in glycated hemoglobin (HbA1c) with insulin glargine was similar to that with NPH insulin. Adult Patients with Type 1 Diabetes In two clinical studies (Studies A and B), adult patients with type 1 diabetes (Study A, n = 585, Study B n = 534) were randomized to 28 weeks of basal-bolus treatment with insulin glargine or NPH insulin. Regular human insulin was administered before each meal. Insulin glargine was administered at bedtime. NPH insulin was administered either as once daily at bedtime or in the morning and at bedtime when used twice daily. In Study A, the average age was 39 years. The majority of patients were White (99%) and 56% were male. The mean BMI was approximately 24.9 kg/m 2 . The mean duration of diabetes was 16 years. In Study B, the average age was 39 years. The majority of patients were White (95%) and 51% were male. The mean BMI was approximately 25.8 kg/m 2 . The mean duration of diabetes was 17 years. In another clinical study (Study C), patients with type 1 diabetes (n = 619) were randomized to 16 weeks of basal-bolus treatment with insulin glargine or NPH insulin. Insulin lispro was used before each meal. Insulin glargine was administered once daily at bedtime and NPH insulin was administered once or twice daily. The average age was 39 years. The majority of patients were White (97%) and 51% were male. The mean BMI was approximately 25.6 kg/m 2 . The mean duration of diabetes was 19 years. In these 3 adult studies, insulin glargine and NPH insulin had similar effects on HbA1c (Table 9) with a similar overall rate of severe symptomatic hypoglycemia [see Adverse Reactions (6.1) ] . Table 9: Type 1 Diabetes Mellitus – Adults Treatment duration Treatment in combination with Study A 28 weeks Regular insulin Study B 28 weeks Regular insulin Study C 16 weeks Insulin lispro Insulin Glargine NPH Insulin Glargine NPH Insulin Glargine NPH Number of subjects treated 292 293 264 270 310 309 HbA1c Baseline HbA1c 8.0 8.0 7.7 7.7 7.6 7.7 Adjusted mean change at study end +0.2 +0.1 -0.2 -0.2 -0.1 -0.1 Treatment Difference (95% CI) +0.1 (0.0; +0.2) +0.1 (-0.1; +0.2) 0.0 (-0.1; +0.1) Basal insulin dose Baseline mean 21 23 29 29 28 28 Mean change from baseline -2 0 -4 +2 -5 +1 Total insulin dose Baseline mean 48 52 50 51 50 50 Mean change from baseline -1 0 0 +4 -3 0 Fasting blood glucose (mg/dL) Baseline mean 167 166 166 175 175 173 Adj. mean change from baseline -21 -16 -20 -17 -29 -12 Body weight (kg) Baseline mean 73.2 74.8 75.5 75.0 74.8 75.6 Mean change from baseline 0.1 -0.0 0.7 1.0 0.1 0.5   Pediatric Patients with Type 1 Diabetes In a randomized, controlled clinical study (Study D), pediatric patients (age range 6 to 15 years) with type 1 diabetes (n = 349) were treated for 28 weeks with a basal-bolus insulin regimen where regular human insulin was used before each meal. Insulin glargine was administered once daily at bedtime and NPH insulin was administered once or twice daily. The average age was 11.7 years. The majority of patients were White (97%) and 52% were male. The mean BMI was approximately 18.9 kg/m 2 . The mean duration of diabetes was 5 years. Similar effects on HbA1c (Table 10) were observed in both treatment groups [see Adverse Reactions (6.1) ] . Table 10: Type 1 Diabetes Mellitus – Pediatric Patients Treatment duration Treatment in combination with Study D 28 weeks Regular insulin Insulin Glargine + Regular insulin NPH+ Regular insulin Number of subjects treated 174 175 HbA1c Baseline mean 8.5 8.8 Change from baseline (adjusted mean) +0.3 +0.3 Difference from NPH (adjusted mean) 0.0 (95% CI) (-0.2; +0.3) Basal insulin dose Baseline mean 19 19 Mean change from baseline -1 +2 Total insulin dose Baseline mean 43 43 Mean change from baseline +2 +3 Fasting blood glucose (mg/dL) Baseline mean 194 191 Mean change from baseline -23 -12 Body weight (kg) Baseline mean 45.5 44.6 Mean change from baseline 2.2 2.5 In a randomized, controlled clinical study (Study E) in 570 adults with type 2 diabetes, insulin glargine was evaluated for 52 weeks in combination with oral anti-diabetic medications (a sulfonylurea, metformin, acarbose, or combinations of these drugs). The average age was 60 years old. The majority of patients were White (93%) and 54% were male. The mean BMI was approximately 29.1 kg/m 2 . The mean duration of diabetes was 10 years. Insulin glargine administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA1c and fasting glucose (Table 11). The rate of severe symptomatic hypoglycemia was similar in insulin glargine and NPH insulin treated patients [see Adverse Reactions (6.1) ] . In a randomized, controlled clinical study (Study F), in adult patients with type 2 diabetes not using oral antidiabetic medications (n = 518), a basal-bolus regimen of insulin glargine once daily at bedtime or NPH insulin administered once or twice daily was evaluated for 28 weeks. Regular human insulin was used before meals, as needed. The average age was 59 years. The majority of patients were White (81%) and 60% were male. The mean BMI was approximately 30.5 kg/m 2 . The mean duration of diabetes was 14 years. Insulin glargine had similar effectiveness as either once- or twice-daily NPH insulin in reducing HbA1c and fasting glucose (Table 11) with a similar incidence of hypoglycemia [see Adverse Reactions (6.1) ] . In a randomized, controlled clinical study (Study G), adult patients with type 2 diabetes were randomized to 5 years of treatment with once-daily insulin glargine or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dosage of insulin glargine or NPH insulin was 10 units daily. Patients who were already treated with NPH insulin either continued on the same total daily NPH insulin dose or started insulin glargine at a dosage that was 80% of the total previous NPH insulin dosage. The primary endpoint for this study was a comparison of the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. HbA1c change from baseline was a secondary endpoint. Similar glycemic control in the 2 treatment groups was desired in order to not confound the interpretation of the retinal data. Patients or study personnel used an algorithm to adjust the insulin glargine and NPH insulin dosages to a target fasting plasma glucose ≤ 100 mg/dL. After the insulin glargine or NPH insulin dosage was adjusted, other anti-diabetic agents, including premeal insulin were to be adjusted or added. The average age was 55 years. The majority of patients were White (85%) and 54% were male. The mean BMI was approximately 34.3 kg/m 2 . The mean duration of diabetes was 11 years. The insulin glargine group had a smaller mean reduction from baseline in HbA1c compared to the NPH insulin group, which may be explained by the lower daily basal insulin doses in the insulin glargine group (Table 11). The incidences of severe symptomatic hypoglycemia were similar between groups [see Adverse Reactions (6.1) ] . Table 11: Type 2 Diabetes Mellitus – Adults Treatment duration Treatment in combination with Study E 52 weeks Oral agents Study F 28 weeks Regular insulin Study G 5 years Regular insulin Insulin Glargine NPH Insulin Glargine NPH Insulin Glargine NPH Number of subjects treated 289 281 259 259 513 504 HbA1c Baseline mean 9.0 8.9 8.6 8.5 8.4 8.3 Adjusted mean change from baseline -0.5 -0.4 -0.4 -0.6 -0.6 -0.8 Insulin Glargine ‒ NPH -0.1 +0.2 +0.2 95% CI for Treatment difference (-0.3; +0.1) (0.0; +0.4) (+0.1; +0.4) Basal insulin dose In Study G, the baseline dose of basal or total insulin was the first available on-treatment dose prescribed during the study (on visit month 1.5). Baseline mean 14 15 44.1 45.5 39 44 Mean change from baseline +12 +9 -1 +7 +23 +30 Total insulin dose Baseline mean 14 15 64 67 48 53 Mean change from baseline +12 +9 +10 +13 +41 +40 Fasting blood glucose (mg/dL) Baseline mean 179 180 164 166 190 180 Adj. mean change from baseline -49 -46 -24 -22 -45 -44 Body weight (kg) Baseline mean 83.5 82.1 89.6 90.7 100 99 Adj. mean change from baseline 2.0 1.9 0.4 1.4 3.7 4.8 Different Timing of Insulin Glargine Administration in Diabetes Type 1 and Diabetes Type 2 The safety and efficacy of once daily insulin glargine administered either at pre-breakfast, pre-dinner, or at bedtime were evaluated in a randomized, controlled clinical study in adult patients with type 1 diabetes (Study H, n = 378). Patients were also treated with insulin lispro at mealtime. The average age was 41 years. All patients were White (100%) and 54% were male. The mean BMI was approximately 25.3 kg/m 2 . The mean duration of diabetes was 17 years. Insulin glargine administered at pre-breakfast or at pre-dinner (both once daily) resulted in similar reductions in HbA1c compared to that with bedtime administration (see Table 12). In these patients, data are available from 8-point home glucose monitoring. The maximum mean blood glucose was observed just prior to insulin glargine injection regardless of time of administration. In this study, 5% of patients in the insulin glargine-breakfast group discontinued treatment because of lack of efficacy. No patients in the other two groups (pre-dinner, bedtime) discontinued for this reason. The safety and efficacy of once daily insulin glargine administered pre-breakfast or at bedtime were also evaluated in a randomized, active-controlled clinical study (Study I, n = 697) in patients with type 2 diabetes not adequately controlled on oral anti-diabetic therapy. All patients in this study also received glimepiride 3 mg daily. The average age was 61 years. The majority of patients were White (97%) and 54% were male. The mean BMI was approximately 28.7 kg/m 2 . The mean duration of diabetes was 10 years. Insulin glargine given before breakfast was at least as effective in lowering HbA1c as insulin glargine given at bedtime or NPH insulin given at bedtime (see Table 12). Table 12: Study of Different Times of Once Daily Insulin Glargine Dosing in Type 1 (Study H) and Type 2 (Study I) Diabetes Mellitus Treatment duration Treatment in combination with Study H 24 weeks Insulin lispro Study I 24 weeks Glimepiride Insulin Glargine Before Breakfast Insulin Glargine Before Dinner Insulin Glargine Bedtime Insulin Glargine Before Breakfast Insulin Glargine Bedtime NPH Bedtime Number of subjects treated Intent-to-treat 112 124 128 234 226 227 HbA1c Baseline mean 7.6 7.5 7.6 9.1 9.1 9.1 Mean change from baseline -0.2 -0.1 0.0 -1.3 -1.0 -0.8 Basal insulin dose (Units) Baseline mean 22 23 21 19 20 19 Mean change from baseline 5 2 2 11 18 18 Total insulin dose (Units) - - - NA Not applicable NA NA Baseline mean 52 52 49 - - - Mean change from baseline 2 3 2 - - - Body weight (kg) Baseline mean 77.1 77.8 74.5 80.7 82 81 Mean change from baseline 0.7 0.1 0.4 3.9 3.7 2.9 Progression of Retinopathy Evaluation in Adults with Diabetes Type 1 and Diabetes Type 2 Insulin glargine was compared to NPH insulin in a 5-year randomized clinical study that evaluated the progression of retinopathy as assessed with fundus photography using a grading protocol derived from the Early Treatment Diabetic Retinopathy Scale (ETDRS). Patients had type 2 diabetes (mean age 55 years) with no (86%) or mild (14%) retinopathy at baseline. Mean baseline HbA1c was 8.4%. The primary outcome was progression by 3 or more steps on the ETDRS scale at study endpoint. Patients with pre-specified post-baseline eye procedures (pan-retinal photocoagulation for proliferative or severe nonproliferative diabetic retinopathy, local photocoagulation for new vessels, and vitrectomy for diabetic retinopathy) were also considered as 3-step progressors regardless of actual change in ETDRS score from baseline. Retinopathy graders were blinded to treatment group assignment. The results for the primary endpoint are shown in Table 13 for both the per-protocol and intent-to-treat populations, and indicate similarity of insulin glargine to NPH in the progression of diabetic retinopathy as assessed by this outcome. In this study, the numbers of retinal adverse events reported for insulin glargine and NPH insulin treatment groups were similar for adult patients with type 1 and type 2 diabetes. Table 13: Number (%) of Patients with 3 or More Step Progression on ETDRS Scale at Endpoint Insulin Glargine (%) NPH (%) Difference Difference = Insulin Glargine – NPH , Using a generalized linear model (SAS GENMOD) with treatment and baseline HbA1c strata (cutoff 9.0%) as the classified independent variables, and with binomial distribution and identity link function (SE) 95% CI for difference Per-protocol 53/374 (14.2%) 57/363 (15.7%) -2.0% (2.6%) -7.0% to +3.1% Intent-to-Treat 63/502 (12.5%) 71/487 (14.6%) -2.1% (2.1%) -6.3% to +2.1% The ORIGIN Study of Major Cardiovascular Outcomes in Patients with Established CV Disease or CV Risk Factors The Outcome Reduction with Initial Glargine Intervention study (i.e., ORIGIN) was an open-label, randomized, 2-by-2, factorial design study. One intervention in ORIGIN compared the effect of insulin glargine to standard care on major adverse cardiovascular (CV) outcomes in 12,537 adults ≥ 50 years of age with: • Abnormal glucose levels (i.e., impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) or early type 2 diabetes mellitus and • Established CV disease or CV risk factors at baseline. The objective of the study was to demonstrate that insulin glargine use could significantly lower the risk of major CV outcomes compared to standard care. There were two coprimary composite CV endpoints: • The first coprimary endpoint was the time to first occurrence of a major adverse CV event defined as the composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. • The second coprimary endpoint was the time to the first occurrence of CV death or nonfatal myocardial infarction or nonfatal stroke or revascularization procedure or hospitalization for heart failure. Patients were randomized to either insulin glargine (N = 6,264) titrated to a goal fasting plasma glucose of ≤ 95 mg/dL or to standard care (N = 6,273). Anthropometric and disease characteristics were balanced at baseline. The mean age was 64 years and 8% of patients were 75 years of age or older. The majority of patients were male (65%). Fifty nine percent were White, 25% were Latin, 10% were Asian and 3% were Black or African American. The median baseline BMI was 29 kg/m 2 . Approximately 12% of patients had abnormal glucose levels (IGT and/or IFG) at baseline and 88% had type 2 diabetes. For patients with type 2 diabetes, 59% were treated with a single oral antidiabetic drug, 23% had known diabetes but were on no antidiabetic drug and 6% were newly diagnosed during the screening procedure. The mean HbA1c (SD) at baseline was 6.5% (1.0). Fifty-nine percent of the patients had a prior CV event and 39% had documented coronary artery disease or other CV risk factors. Vital status was available for 99.9% and 99.8% of patients randomized to insulin glargine and standard care respectively at end of study. The median duration of follow-up was 6.2 years (range: 8 days to 7.9 years). The mean HbA1c (SD) at the end of the study was 6.5% (1.1) and 6.8% (1.2) in the insulin glargine and standard care group respectively. The median dose of insulin glargine at end of study was 0.45 U/kg. Eighty-one percent of patients randomized to insulin glargine were using insulin glargine at end of the study. The mean change in body weight from baseline to the last treatment visit was 2.2 kg greater in the insulin glargine group than in the standard care group. Overall, the incidence of major adverse CV outcomes was similar between groups (see Table 14). All-cause mortality was also similar between groups. Table 14: Cardiovascular Outcomes in ORIGIN in Patients with Established CV Disease or CV Risk Factors – Time to First Event Analyses Insulin Glargine N = 6,264 Standard Care N = 6,273 Insulin Glargine vs Standard Care n (Events per 100 PY) n (Events per 100 PY) Hazard Ratio (95% CI) Coprimary endpoints CV death, nonfatal myocardial infarction, or nonfatal stroke 1041 (2.9) 1013 (2.9) 1.02 (0.94, 1.11) CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure or revascularization procedure 1792 (5.5) 1727 (5.3) 1.04 (0.97, 1.11) Components of coprimary endpoints CV death 580 576 1.00 (0.89, 1.13) Myocardial Infarction (fatal or nonfatal) 336 326 1.03 (0.88, 1.19) Stroke (fatal or nonfatal) 331 319 1.03 (0.89, 1.21) Revascularizations 908 860 1.06 (0.96, 1.16) Hospitalization for heart failure 310 343 0.90 (0.77, 1.05) In the ORIGIN study, the overall incidence of cancer (all types combined) or death from cancer (Table 15) was similar between treatment groups. Table 15: Cancer Outcomes in ORIGIN – Time to First Event Analyses Insulin Glargine N = 6,264 Standard Care N = 6,273 Insulin Glargine vs Standard Care n (Events per 100 PY) n (Events per 100 PY) Hazard Ratio (95% CI) Cancer endpoints Any cancer event (new or recurrent) 559 (1.56) 561 (1.56) 0.99 (0.88, 1.11) New cancer events 524 (1.46) 535 (1.49) 0.96 (0.85, 1.09) Death due to Cancer 189 (0.51) 201 (0.54) 0.94 (0.77, 1.15)

Insulin Glargine-yfgn (in′ su lin glar′ jeen) injection for subcutaneous use VIAL: 100 units/mL (U-100) This product is SEMGLEE (insulin glargine-yfgn). Do not share your syringes with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them. What is Insulin Glargine-yfgn? Insulin Glargine-yfgn is a long-acting man-made-insulin used to control high blood sugar in adults and children with diabetes mellitus. Insulin Glargine-yfgn is not for use to treat diabetic ketoacidosis. Who should not use Insulin Glargine-yfgn? Do not use Insulin Glargine-yfgn if you: • are having an episode of low blood sugar (hypoglycemia). • have an allergy to insulin glargine products or any of the ingredients in Insulin Glargine-yfgn . See the end of this Patient Information leaflet for a complete list of ingredients in Insulin Glargine-yfgn. What should I tell my healthcare provider before using Insulin Glargine-yfgn? Before using Insulin Glargine-yfgn , tell your healthcare provider about all your medical conditions including if you: • have liver or kidney problems. • take other medicines, especially ones called TZDs (thiazolidinediones). • have heart failure or other heart problems. If you have heart failure, it may get worse while you take TZDs with Insulin Glargine-yfgn . • are pregnant, planning to become pregnant, or are breastfeeding. It is not known if Insulin Glargine-yfgn may harm your unborn baby or breastfeeding baby. Tell your healthcare provider about all the medicines you take including prescription and over-the-counter medicines, vitamins, and herbal supplements. Before you start using Insulin Glargine-yfgn , talk to your healthcare provider about low blood sugar and how to manage it. How should I use Insulin Glargine-yfgn? • Read the detailed Instructions for Use that come with your Insulin Glargine-yfgn . • Use Insulin Glargine-yfgn exactly as your healthcare provider tells you to. Your healthcare provider should tell you how much Insulin Glargine-yfgn to use and when to use it. • Know the amount of Insulin Glargine-yfgn you use. Do not change the amount of Insulin Glargine-yfgn you use unless your healthcare provider tells you to. • Check your Insulin label each time you give your injection to make sure you are using the correct Insulin. • Do not re-use needles. Always use a new needle for each injection. Re-use of needles increases your risk of having blocked needles, which may cause you to get the wrong dose of Insulin Glargine-yfgn. Using a new needle for each injection lowers your risk of getting an infection. • You may take Insulin Glargine-yfgn at any time during the day but you must take it at the same time every day. • Only use Insulin Glargine-yfgn that is clear and colorless. If your Insulin Glargine-yfgn is cloudy or slightly colored, return it to your pharmacy for a replacement. • Insulin Glargine-yfgn is injected under the skin (subcutaneously) of your upper legs (thighs), upper arms, or stomach area (abdomen). • Do not use Insulin Glargine-yfgn in an insulin pump or inject Insulin Glargine-yfgn into your vein (intravenously). • Change (rotate) sites within the area you chose with each dose to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the sites. o Do not use the exact same spot for each injection. o Do not inject where the skin has pits, is thickened, or has lumps. o Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin. • Do not mix Insulin Glargine-yfgn with any other type of insulin or liquid medicine. • Check your blood sugar levels. Ask your healthcare provider what your blood sugar should be and when you should check your blood sugar levels. Keep Insulin Glargine-yfgn and all medicines out of the reach of children. Your dose of Insulin Glargine-yfgn may need to change because of: • a change in level of physical activity or exercise, weight gain or loss, increased stress, illness, change in diet, or because of the medicines you take. What should I avoid while using Insulin Glargine-yfgn? While using Insulin Glargine-yfgn do not: • drive or operate heavy machinery, until you know how Insulin Glargine-yfgn affects you. • drink alcohol or use over-the-counter medicines that contain alcohol. What are the possible side effects of Insulin Glargine-yfgn and other insulins? Insulin Glargine-yfgn may cause serious side effects that can lead to death, including: • low blood sugar (hypoglycemia). Signs and symptoms that may indicate low blood sugar include: o dizziness or light-headedness, sweating, confusion, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability or mood change, hunger. • severe allergic reaction (whole body reaction). Get medical help right away if you have any of these signs or symptoms of a severe allergic reaction: o a rash over your whole body, trouble breathing, a fast heartbeat, or sweating. • low potassium in your blood (hypokalemia). • heart failure. Taking certain diabetes pills called TZDs (thiazolidinediones) with Insulin Glargine-yfgn may cause heart failure in some people. This can happen even if you have never had heart failure or heart problems before. If you already have heart failure it may get worse while you take TZDs with Insulin Glargine-yfgn . Your healthcare provider should monitor you closely while you are taking TZDs with Insulin Glargine-yfgn . Tell your healthcare provider if you have any new or worse symptoms of heart failure including: o shortness of breath, swelling of your ankles or feet, sudden weight gain. Treatment with TZDs and Insulin Glargine-yfgn may need to be changed or stopped by your healthcare provider if you have new or worse heart failure. Get emergency medical help if you have: • trouble breathing; shortness of breath; fast heartbeat; swelling of your face, tongue, or throat; sweating; extreme drowsiness; dizziness; confusion. The most common side effects of Insulin Glargine-yfgn include: • low blood sugar (hypoglycemia); weight gain; allergic reactions, including reactions at your injection site; skin thickening or pits at the injection site (lipodystrophy). These are not all the possible side effects of Insulin Glargine-yfgn . Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of Insulin Glargine-yfgn . Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Insulin Glargine-yfgn for a condition for which it was not prescribed. Do not give Insulin Glargine-yfgn to other people, even if they have the same symptoms that you have. It may harm them. This Patient Information leaflet summarizes the most important information about Insulin Glargine-yfgn . If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Insulin Glargine-yfgn that is written for healthcare professionals. What are the ingredients in Insulin Glargine-yfgn? • Active ingredient: insulin glargine-yfgn • 10 mL vial inactive ingredients: glycerol, metacresol, polysorbate-20, zinc chloride, and Water for Injection. Hydrochloric acid and sodium hydroxide may be added to adjust the pH. For more information, call Biocon Biologics at 1-833-986-1468 Manufactured by: Biocon Biologics Inc., 245 Main St, 2nd Floor, Cambridge, MA 02142 U.S.A. U.S. License No. 2324 Product of Malaysia This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 11/2023

NDC 83257-015-32 Rx only Insulin Glargine-yfgn Injection For Single Patient Use Only 100 units/mL (U-100) For subcutaneous use only Dispense in this sealed carton Do not mix with other insulins Use only if solution is clear and colorless with no particles visible *Needles not included (see top panel) This product is Semglee. Five 3 mL Prefilled Pens Each mL contains 100 units of insulin Glargine-yfgn, and inactive ingredients: glycerol (20 mg), metacresol (2.7 mg), zinc chloride (content adjusted to provide 30 mcg zinc ion), and Water for Injection, USP. The pH is approximately 4. The pH is adjusted by addition of aqueous solutions of hydrochloric acid and/or sodium hydroxide. Recommended dosage: see Prescribing Information. As with any drug, if you are pregnant or nursing a baby, seek professional advice when using this product. Any change of insulin should be made cautiously and only under medical supervision. Storage:  Refrigerate at 2º to 8ºC (36º to 46ºF) until first use. Avoid freezing. Discard if frozen. After first use an insulin Glargine-yfgn pen, store the pen at room temperature (up to 30ºC [86ºF]) and discard after 28 days. Protect from direct heat and light. WARNING: Keep this and all medication out of the reach of children. Use within 28 days after initial use. *BD ® Ultra-Fine needles are compatible with insulin Glargine injection. These are sold separately and manufactured by BD. BD is a registered trademark of Becton, Dickinson, and Company. © 2023 Biocon Biologics Inc. Manufactured by: Biocon Biologics Inc. , 245 Main St, 2nd Floor Cambridge, MA 02142, U.S.A. U.S. License No. 2324 Product of Malaysia Insulin Glargine-yfgn Injection, 100 units/mL (U-100) - Pen