Basaglar

Name: Basaglar

Basaglar Food Interactions

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Basaglar, there are no specific foods that you must exclude from your diet when receiving this medication.

Before Using Basaglar

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of Basaglar® or Lantus® to treat type 1 diabetes in children 6 years of age and older. However, safety and efficacy of Lantus® have not been established in children younger than 6 years of age with type 1 diabetes and in children with type 2 diabetes.

Appropriate studies have not been performed on the relationship of age to the effects of Toujeo® in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of insulin glargine in the elderly. However, elderly patients are more likely to have unwanted effects, which may require caution in patients receiving this medicine.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Balofloxacin
  • Besifloxacin
  • Ciprofloxacin
  • Enoxacin
  • Fleroxacin
  • Flumequine
  • Gatifloxacin
  • Gemifloxacin
  • Lanreotide
  • Levofloxacin
  • Liraglutide
  • Lomefloxacin
  • Metreleptin
  • Moxifloxacin
  • Nadifloxacin
  • Norfloxacin
  • Octreotide
  • Ofloxacin
  • Pasireotide
  • Pazufloxacin
  • Pefloxacin
  • Pioglitazone
  • Pramlintide
  • Prulifloxacin
  • Rosiglitazone
  • Rufloxacin
  • Sparfloxacin
  • Thioctic Acid
  • Tosufloxacin

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acebutolol
  • Albiglutide
  • Atenolol
  • Betaxolol
  • Bisoprolol
  • Carteolol
  • Carvedilol
  • Celiprolol
  • Dulaglutide
  • Esmolol
  • Exenatide
  • Furazolidone
  • Iproniazid
  • Isocarboxazid
  • Labetalol
  • Levobunolol
  • Linezolid
  • Lixisenatide
  • Methylene Blue
  • Metipranolol
  • Metoprolol
  • Moclobemide
  • Nadolol
  • Nebivolol
  • Nialamide
  • Oxprenolol
  • Penbutolol
  • Phenelzine
  • Pindolol
  • Practolol
  • Procarbazine
  • Propranolol
  • Rasagiline
  • Safinamide
  • Selegiline
  • Sotalol
  • Timolol
  • Tranylcypromine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Congestive heart failure or
  • Hypokalemia (low potassium in the blood)—Use with caution. May make these conditions worse.
  • Emotional disturbances or
  • Illness or
  • Infection or
  • Stress—These conditions could change blood sugar levels, and may change the amount of insulin you need.
  • Hypoglycemia (low blood sugar)—Should not be used in patients with this condition. If you have low blood sugar and take insulin, your blood sugar may reach dangerously low levels.
  • Kidney disease or
  • Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Use in specific populations

Pregnancy

Pregnancy Category C

Risk Summary

All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control. It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. In patients with diabetes or gestational diabetes, insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential in these patients. Therefore, female patients should be advised to tell their physicians if they intend to become, or if they become pregnant while taking Basaglar.

Human data

There are no well-controlled clinical studies of the use of insulin glargine in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal data

Subcutaneous reproduction and teratology studies have been performed with another insulin glargine product and with regular human insulin in rats and Himalayan rabbits. This other insulin glargine product was given to female rats before mating, during mating, and throughout pregnancy at dose up to 0.36 mg/kg/day, which is approximately 7 times the recommended human subcutaneous starting dose of 10 units/day (0.008 mg/kg/day) based on mg/m2. In rabbits, doses of 0.072 mg/kg/day, which is approximately 2 times the recommended human subcutaneous starting dose of 10 units/day (0.008 mg/kg/day), based on mg/m2, were administered during organogenesis. The effects of this other insulin glargine product did not generally differ from those observed with regular human insulin in rats and 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.

Nursing Mothers

Endogenous insulin is present in human milk; it is unknown whether insulin glargine is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, caution should be exercised when Basaglar is administered to a nursing woman. Use of Basaglar is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses.

Pediatric Use

The safety and effectiveness of Basaglar have been established in pediatric patients (age 6 to 15 years) with type 1 diabetes based on an adequate and well-controlled trial of another insulin glargine product, 100 units/mL, in pediatric patients (age 6 to 15 years) with type 1 diabetes and additional data in adults with type 1 diabetes [see Clinical Studies (14.2)]. The safety and effectiveness of Basaglar in pediatric patients younger than 6 years of age with type 1 diabetes and pediatric patients with type 2 diabetes has not been established.

The dosage recommendation when changing to Basaglar in pediatric patients (age 6 to 15 years) with type 1 diabetes is the same as that described for adults [see Dosage and Administration (2.3, 2.4) and Clinical Studies (14)]. As in adults, the dosage of Basaglar must be individualized in pediatric patients (age 6 to 15 years) with type 1 diabetes based on metabolic needs and frequent monitoring of blood glucose.

In the pediatric clinical trial, pediatric patients (age 6 to 15 years) with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in trials with type 1 diabetes [see Adverse Reactions (6.1)].

Geriatric Use

Of the total number of subjects in clinical studies of patients with type 2 diabetes who were treated with Basaglar or another insulin glargine product, 100 units/mL, each in combination with oral agents in a controlled clinical trial environment, 28.3% were 65 and over, while 4.5% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Nevertheless, caution should be exercised when Basaglar is administered to geriatric patients. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in the elderly.

Renal Impairment

The effect of renal impairment on the pharmacokinetics of Basaglar has not been studied. Some studies with human insulin have shown increased circulating levels of insulin in patients with renal failure. Frequent glucose monitoring and dose adjustment may be necessary for Basaglar in patients with renal impairment [see Warnings and Precautions (5.3)].

Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of Basaglar has not been studied. However, as with all insulin products, more frequent glucose monitoring and dose adjustment may be necessary for Basaglar in patients with hepatic impairment [see Warnings and Precautions (5.3)].

Obesity

In controlled clinical trials, subgroup analyses based on BMI did not show differences in safety and efficacy between Basaglar and another insulin glargine product, 100 units/mL.

Clinical Studies

Overview of Clinical Studies

The safety and effectiveness of another insulin glargine product, 100 units/mL, 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 adults and 349 pediatric patients with type 1 diabetes mellitus and 1,563 adult patients with type 2 diabetes mellitus (see Tables 8, 9, 11, and 12). In general, the reduction in glycated hemoglobin (HbA1c) with this other insulin glargine product was similar to that with NPH insulin.

Clinical Studies in Adult and Pediatric Patients with Type 1 Diabetes

Patients with inadequately controlled type 1 diabetes participated in a 24-week open-label, active-controlled study with a 28 week extension to evaluate the glucose lowering effect of once-daily Basaglar compared to that of once-daily administration of another insulin glargine product, 100 units/mL, or a non-U.S.-approved insulin glargine product, 100 units/mL, (comparator insulin glargine products, 100 units/mL) both in combination with mealtime insulin lispro. Randomized were 535 adults with type 1 diabetes. Mean age was 41.2 years and mean duration of diabetes was 16.39 years. 57.9% were male. 74.5% were Caucasian, 2.1% Black or African American and 4.3% American Indian or Alaskan native. 3.9% were Hispanic. 73.5 percent of patients had GFR>90 mL/min/1.73m2. The mean BMI was approximately 25.54 kg/m2. At week 24, treatment with Basaglar provided a mean reduction in HbA1c that was non-inferior to that achieved with comparator insulin glargine products, 100 units/mL (see Table 7).

Table 7: Type 1 Diabetes Mellitus – Adult (Basaglar plus Mealtime insulin versus Comparator Insulin Glargine Products, 100 units/mL, plus Mealtime Insulin)

a One patient randomized to the Basaglar group was not included in the Full Analysis Set.

b “Comparator insulin glargine products, 100 units/mL” refers to another insulin glargine product, 100 units/mL, and a non-U.S.-approved insulin glargine product, 100 units/mL, used in this study.

c ANCOVA Model includes treatment, country and time of baseline basal insulin injection (daytime or evening/bedtime) as fixed effects and baseline HbA1c as covariate.

d The results were calculated based on the number of patients in the Full Analysis Set using their last observed post-baseline value of HbA1c. Observed HbA1c data at 24 weeks were available from 256 (95.5%) and 258 (96.6%) subjects randomized to the Basaglar and comparator insulin glargine products, 100 units/mL, groups, respectively.

Efficacy Parameter Basaglar + insulin lispro
(N=268a)
Comparator Insulin Glargine Products, 100 units/mLb + insulin lispro
(N=267)
HbA1c (%)
     Baseline (mean) 7.75 7.79
     Change from baseline (adjusted meanc,d) -0.35 -0.46
     Difference from comparator (adjusted meanc,d)
(95% CI)
0.11

(-0.002, 0.219)
Proportion of patients achieving HbA1c <7%d 34.5% 32.2%

In two clinical studies (Studies A and B), patients with type 1 diabetes (Study A; n=585, Study B; n=534) were randomized to 28 weeks of basal-bolus treatment with another insulin glargine product, 100 units/mL, or NPH insulin. Regular human insulin was administered before each meal. This other insulin glargine product was administered at bedtime. NPH insulin was administered once daily at bedtime or in the morning and at bedtime when used twice daily. In Study A, the average age was 39.2 years. The majority of patients were Caucasian (99%) and 55.7% were male. The mean BMI was approximately 24.9 kg/m2. The mean duration of diabetes was 15.5 years. In Study B, the average age was 38.5 years. The majority of patients were Caucasian (95.3%) and 50.6% were male. The mean BMI was approximately 25.8 kg/m2. The mean duration of diabetes was 17.4 years.

In another clinical study (Study C), patients with type 1 diabetes (n=619) were randomized to 16 weeks of basal-bolus treatment with another insulin glargine product, 100 units/mL, or NPH insulin. Insulin lispro was used before each meal. This other insulin glargine product was administered once daily at bedtime and NPH insulin was administered once or twice daily. The average age was 39.2 years. The majority of patients were Caucasian (96.9%) and 50.6% were male. The mean BMI was approximately 25.6 kg/m2. The mean duration of diabetes was 18.5 years.

In these 3 studies, another insulin glargine product, 100 units/mL, and NPH insulin had similar effects on HbA1c (see Table 8) with a similar overall rate of hypoglycemia [see Adverse Reactions (6.1)].

Table 8: Type 1 Diabetes Mellitus – Adult (Another Insulin Glargine Product, 100 units/mL, versus NPH)
Treatment duration
Treatment in combination with
Study A
28 weeks
Regular insulin
Study B
28 weeks
Regular insulin
Study C
16 weeks
Insulin lispro
Another Insulin Glargine Product NPH Another Insulin Glargine Product NPH Another Insulin Glargine Product NPH
Number of subject treated 292 293 264 270 310 309
HbA1c (%)
Baseline (mean) 8.0 8.0 7.7 7.7 7.6 7.7
Adjusted mean change at trial 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)
Fasting blood glucose (mg/dL)
Baseline (mean) 167 166 166 175 175 173
Adjusted mean change at trial end -21 -16 -20 -17 -29 -12

Type 1 Diabetes – Pediatric (see Table 9)

The efficacy of Basaglar to improve glycemic control in pediatric patients with type 1 diabetes mellitus is based on an adequate and well-controlled trial of another insulin glargine product, 100 units/mL, in pediatric patients with type 1 diabetes mellitus (Study D). In this randomized, active-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. Patients were randomized to either this other insulin glargine product administered once daily at bedtime or NPH insulin administered once or twice daily. The average age was 11.7 years. The majority of patients were Caucasian (96.8%) and 51.9% were male. The mean BMI was approximately 18.9 kg/m2. The mean duration of diabetes was 4.8 years. Similar effects on HbA1c (see Table 9) were observed in both treatment groups.

Table 9: Type 1 Diabetes Mellitus – Pediatric (Another Insulin Glargine Product, 100 units/mL, plus Regular Insulin versus NPH plus Regular Insulin)
Study D
Another Insulin Glargine Product + 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)
(95% CI)
0.0
(-0.2; +0.3)
Fasting blood glucose (mg/dL)
Baseline mean 194 191
Mean change from baseline -23 -12

Clinical Studies in Adults with Type 2 Diabetes

Patients with type 2 diabetes participated in a double-blind, active-controlled study to evaluate the glucose lowering effect of once-daily Basaglar plus oral antidiabetic medication (OAM) compared to that of another insulin glargine product, 100 units/mL, or a non-U.S.-approved insulin glargine product, 100 units/mL (comparator insulin glargine products, 100 units/mL) administered once-daily along with OAMs. Patients were either insulin naïve (approximately 60%) and had failed to achieve adequate glycemic control on at least 2 OAMs, or were already on another insulin glargine product, 100 units/mL, or a non-U.S.-approved insulin glargine product, 100 units/mL, along with at least 2 OAMs with adequate or inadequate glycemic control (approximately 40%). A total of 759 patients were randomized. Three patients randomized to Basaglar did not receive study drug and were not included in efficacy analysis. The average age was approximately 59 years. The majority of patients were White (78%) and 50% of the patients were male. Sixty-eight percent of patients had GFR>90 mL/min/1.73m2. The mean BMI was approximately 32 kg/m2. At week 24, treatment with Basaglar provided a mean reduction in HbA1c that was non-inferior to that achieved with comparator insulin glargine products, 100 units/mL (see Table 10).

Table 10: Type 2 Diabetes Mellitus – Adult (Basaglar plus Oral Antidiabetic Medications versus Comparator Insulin Glargine Products, 100 units/mL, plus Oral Antidiabetic Medications)

a Three patients randomized to Basaglar did not receive study drug and were not included in the Full Analysis Set.

b “Comparator insulin glargine products, 100 units/mL” refers to another insulin glargine product, 100 units/mL, and a non-U.S.-approved insulin glargine product, 100 units/mL, used in this study.

c ANCOVA Model includes treatment, country, sulfonylurea use and time of baseline basal insulin injection (daytime or evening/bedtime) as fixed effects and baseline HbA1c as covariate.

d The results were calculated based on the number of patients in the Full Analysis Set using their last observed post-baseline value of HbA1c. Observed HbA1c data at 24 weeks were available from 331 (88%) and 329 (87%) subjects randomized to the Basaglar and comparator insulin glargine products, 100 units/mL, groups, respectively.

Basaglar + Oral Antidiabetic Medication
(N=376)a
Comparator Insulin Glargine Products, 100 units/mLb + Oral Antidiabetic Medication (N=380)
HbA1c (%)
Baseline (mean) 8.35 8.31
Change from baseline (adjusted meanc,d) -1.3 -1.3
Difference from comparator (adjusted meanc,d)
(95% CI)
0.05
(-0.07, 0.17)
Proportion of patients achieving HbA1c <7%d 48.8% 52.5%

In a randomized, controlled clinical study (Study E) (n=570), another insulin glargine product, 100 units/mL, was evaluated for 52 weeks in combination with oral anti-diabetic medications (a sulfonylurea, metformin, acarbose, or combination of these drugs). The average age was 59.5 years. The majority of patients were Caucasian (92.8%) and 53.7% were male. The mean BMI was approximately 29.1 kg/m2. The mean duration of diabetes was 10.3 years. This other insulin glargine product administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA1c and fasting glucose (see Table 11). The rate of hypoglycemia was similar in this other insulin glargine product and NPH insulin treated patients [see Adverse Reactions (6.1)].

In a randomized, controlled clinical study (Study F), in patients with type 2 diabetes not using oral anti-diabetic medications (n=518), a basal-bolus regimen of another insulin glargine product, 100 units/mL, 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 59.3 years. The majority of patients were Caucasian (80.7%) and 60% were male. The mean BMI was approximately 30.5 kg/m2. The mean duration of diabetes was 13.7 years. This other insulin glargine product had similar effectiveness as either once- or twice daily NPH insulin in reducing HbA1c and fasting glucose (see Table 11) with a similar incidence of hypoglycemia [see Adverse Reactions (6.1)].

In a randomized, controlled clinical study (Study G), patients with type 2 diabetes were randomized to 5 years of treatment with another insulin glargine product, 100 units/mL, once-daily or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dose of this other insulin glargine product 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 this other insulin glargine product at a dose that was 80% of the total previous NPH insulin dose. The primary endpoint for this study was a comparison of the progression of diabetic retinopathy by 3 or more steps on the 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 this other insulin glargine product and NPH insulin doses to a target fasting plasma glucose ≤100 mg/dL. After this other insulin glargine product or NPH insulin dose was adjusted, other anti-diabetic agents, including pre-meal insulin were to be adjusted or added. The average age was 55.1 years. The majority of patients were Caucasian (85.3%) and 53.9% were male. The mean BMI was approximately 34.3 kg/m2. The mean duration of diabetes was 10.8 years. This other insulin glargine product 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 this other insulin glargine product group (see Table 11). Both treatment groups had a similar incidence of reported symptomatic hypoglycemia. The incidence of severe symptomatic hypoglycemia in the ORIGIN Trial is given in Table 5 [see Adverse Reactions (6.1)].

Table 11: Type 2 Diabetes Mellitus – Adult (Another Insulin Glargine Product, 100 units/mL, versus NPH)
Treatment duration
Treatment in combination with
Study E
52 weeks
Oral agents
Study F
28 weeks
Regular insulin
Study G
5 years
Regular insulin
Another Insulin Glargine Product NPH Another Insulin Glargine Product NPH Another Insulin Glargine Product 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
Another insulin glargine product, 100 units/mL – NPH -0.1 +0.2 +0.2
95% CI for Treatment difference (-0.3; +0.1) (0.0; +0.4) (+0.1; +0.4)
Fasting blood glucose (mg/dL)
Baseline mean 179 180 164 166 190 180
Adjusted mean change from baseline -49 -46 -24 -22 -45 -44

Another Insulin Glargine Product, 100 units/mL, Timing of Daily Dosing (see Table 12)

The safety and efficacy of this other insulin glargine product administered pre-breakfast, pre-dinner, or at bedtime were evaluated in a randomized, controlled clinical study in patients with type 1 diabetes (Study H; n=378). Patients were also treated with insulin lispro at mealtime. The average age was 40.9 years. All patients were Caucasian (100%) and 53.7% were male. The mean BMI was approximately 25.3 kg/m2. The mean duration of diabetes was 17.3 years. This other insulin glargine product administered at different times of the day 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 injection of this other insulin glargine product regardless of time of administration.

In this study, 5% of patients in this other insulin glargine product-breakfast arm discontinued treatment because of lack of efficacy. No patients in the other two arms discontinued for this reason. The safety and efficacy of this other insulin glargine product 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 60.8 years. The majority of patients were Caucasian (96.6%) and 53.7% were male. The mean BMI was approximately 28.7 kg/m2. The mean duration of diabetes was 10.1 years. This other insulin glargine product given before breakfast was at least as effective in lowering HbA1c as this other insulin glargine product given at bedtime or NPH insulin given at bedtime (see Table 12).

Table 12: Type 1 Diabetes Mellitus – Adults (Another Insulin Glargine Product, 100 units/mL, plus Insulin Lispro) and Type 2 Diabetes Mellitus – Adults (Another Insulin Glargine Product, 100 units/mL, plus Glimepiride versus NPH plus Glimepiride)

a Intent to treat.

b Total number of patients evaluable for safety.

c Not applicable.

Treatment duration
Treatment in combination with
Study H
24 weeks
Insulin lispro
Study I
24 weeks
Glimepiride
Another Insulin Glargine Product Breakfast Another Insulin Glargine Product Dinner Another Insulin Glargine Product Bedtime Another Insulin Glargine Product Breakfast Another Insulin Glargine Product Bedtime NPH
Bedtime
Number of subjects treateda 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

Five-year Trial Evaluating the Progression of Retinopathy

Retinopathy was evaluated in clinical studies with another insulin glargine product, 100 units/mL, by analysis of reported retinal adverse events and fundus photography. The numbers of retinal adverse events reported for this other insulin glargine product and NPH insulin treatment groups were similar for patients with type 1 and type 2 diabetes.

Another insulin glargine product, 100 units/mL, was compared to NPH insulin in a 5-year randomized clinical trial 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 progressions 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 this other insulin glargine product to NPH in the progression of diabetic retinopathy as assessed by this outcome.

Table 13: Number (%) of Patients with 3 or More Step Progression on ETDRS Scale at Endpoint

a Difference = another insulin glargine product, 100 units/mL – NPH.

b 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.

Another Insulin Glargine Product, 100 units/mL (%) NPH (%) Differencea,b (SE) 95% CI for difference
Per-protocol 53/374 (14.2%) 57/363 (15.5%) -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

The Outcome Reduction with Initial Glargine Intervention trial (i.e., ORIGIN) was an open-label, randomized, 2-by-2, factorial design study. One intervention in ORIGIN compared the effect of another insulin glargine product, 100 units/mL, to standard care on major adverse cardiovascular outcomes in 12,537 participants ≥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 cardiovascular (i.e., CV) disease or CV risk factors at baseline.

The objective of the trial was to demonstrate that use of this other insulin glargine product could significantly lower the risk of major cardiovascular outcomes compared to standard care. Two co-primary composite cardiovascular endpoints were used in ORIGIN. The first co-primary endpoint was the time to first occurrence of a major adverse cardiovascular event defined as the composite of CV death, nonfatal myocardial infarction and nonfatal stroke. The second co-primary 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.

Participants were randomized to either this other insulin glargine product (N=6264) titrated to a goal fasting plasma glucose of ≤95 mg/dL or to standard care (N=6273). Anthropometric and disease characteristics were balanced at baseline. The mean age was 64 years and 8% of participants were 75 years of age or older. The majority of participants were male (65%). Fifty nine percent were Caucasian, 25% were Latin, 10% were Asian and 3% were Black. The median baseline BMI was 29 kg/m2. Approximately 12% of participants 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 participants had had a prior cardiovascular event and 39% had documented coronary artery disease or other cardiovascular risk factors.

Vital status was available for 99.9% and 99.8% of participants randomized to this other insulin glargine product and standard care respectively at end of trial. 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 trial was 6.5% (1.1) and 6.8% (1.2) in this other insulin glargine product and standard group respectively. The median dose of this other insulin glargine product at end of trial was 0.45 U/kg. Eighty-one percent of patients randomized to this other insulin glargine product were using this other insulin glargine product at end of the study. The mean change in body weight from baseline to the last treatment visit was 2.2 kg greater in this other insulin glargine group than in the standard care group.

Overall, the incidence of major adverse cardiovascular outcomes was similar between groups (see Table 14). All-cause mortality was also similar between groups.

Table 14: Cardiovascular Outcomes in ORIGIN – Time to First Event Analyses
Another Insulin Glargine Product, 100 units/mL
N=6264
Standard Care

N=6273
Another Insulin Glargine Product, 100 units/mL vs. Standard Care
n
(Events per 100 PY)
n
(Events per 100 PY)

Hazard Ratio (95% CI)
Co-primary 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 co-primary 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 trial, the overall incidence of cancer (all types combined) or death from cancer in the ORIGIN trial (see Table 15) was similar between treatment groups.

Table 15: Cancer Outcomes in ORIGIN – Time to First Event Analyses
Another Insulin Glargine Product, 100 units/mL
N=6264
Standard Care

N=6273
Another Insulin Glargine Product, 100 units/mL 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)

What is Basaglar?

Basaglar (insulin glargine) is a long-acting insulin that starts to work several hours after injection and keeps working evenly for 24 hours. Insulin is a hormone that works by lowering levels of glucose (sugar) in the blood.

Basaglar is used to improve blood sugar control in adults and children with diabetes mellitus.

Basaglar is used to treat type 1 or type 2 diabetes in adults, and type 1 diabetes children who are at least 6 years old.

Some brands of insulin glargine are for use only in adults. Carefully follow all instructions for the brand of insulin glargine you are using.

Insulin glargine Breastfeeding Warnings

Use is considered acceptable; caution is recommended. Excreted into human milk: Yes Comments: Women who are breastfeeding may require adjustments in insulin dose and diet.

Exogenous insulins, including the newer biosynthetic insulins (i.e. aspart, detemir, glargine, glulisine, lispro) appear to be excreted into breast milk. Insulin is a protein that is inactivated if taken by mouth. If absorbed, it would be destroyed in the digestive tract of the infant. Lactation onset occurs later in women with type 1 diabetes, and there is an even greater delay in those with poor glucose control. However, once established lactation persists. Insulin requirements are generally lower in women who breastfeed, most likely due to glucose being used for milk production.

(web3)