SEMGLEE™ clinical trials have shown non-inferior efficacy and safety to reference insulin glargine1-3

SEMGLEE Efficacy

SEMGLEE lowers HbA1c and fasting plasma glucose (FPG) in patients with Type 1 Diabetes in a manner similar to the reference product.2

SEMGLEE clinical trials demonstrated non-inferiority to reference insulin glargine in both adult and pediatric patients with Type 1 Diabetes.1

In patients with type 1 diabetes, a 24 week multicenter, open-label, randomized, active-controlled study to evaluate the glucose lowering effect of once-daily SEMGLEE compared to that of once-daily administration of reference insulin glargine product, 100 units/mL, in combination with mealtime insulin lispro was conducted. Mean age was 42 years, the majority of patients were Caucasian, 94.6%, mean BMI was 26.5 kg/m2, mean duration of diabetes prior to entry into the study was 19 years, the mean exposure of 280 patients to SEMGLEE during the study was 50 weeks. At week 24, treatment with SEMGLEE was non-inferior to the reference insulin glargine product with regard to the mean change in HbA1c over 24 weeks of treatment.


Efficacy Table1

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 reference 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 either as once daily at bedtime or in the morning and at bedtime when used twice daily.

In another clinical study (Study C), patients with type 1 diabetes (n = 619) were randomized to 16 weeks of basal-bolus treatment with reference 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.

In these 3 studies, reference insulin glargine product, 100 units/mL and NPH insulin had similar effects on HbA1c.

Efficacy Table2

Type 1 Diabetes – Pediatrics
The safety and effectiveness of SEMGLEE to improve glycemic control in pediatric patients with type 1 diabetes mellitus have been established in pediatric patients. The use of SEMGLEE for this indication is based upon an adequate and well-controlled trial of reference insulin glargine product in pediatric patients age 6 to 15 years with type 1 diabetes and additional data in adults with type 1 diabetes. In the pediatric clinical trial, pediatric patients with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in trials with type 1 diabetes.

The safety and effectiveness of SEMGLEE in pediatric patients younger than 6 years of age with type 1 diabetes and pediatric patients with type 2 diabetes have not been established.

Pediatric patients (age range 6 to 15 years) with type 1 diabetes (n = 349) in a randomized, controlled clinical study (Study D), were treated for 28 weeks with a basal-bolus insulin regimen where regular human insulin was used before each meal. Other insulin glargine product was administered once daily at bedtime and NPH insulin was administered once or twice daily. The average age was 11.7 years.  

Efficacy
In the INSTRIDE 1 trial, the mean change in HbA1c from baseline to week 24 among Type 1 diabetic patients was non-inferior between SEMGLEE and the reference insulin glargine groups.2

INSTRIDE 1 Study Design2
Primary Endpoint - Change in HbA1c from baseline to week 24.
Secondary Endpoints - Included changes in FPG, insulin dose, SMBG and immunogenicity.
Multicentre, open-label, randomized, parallel group, 52-week trial.
558 patients with type 1 diabetes, with or without prior insulin use: 336 males and 222 females,
aged 18-65 years, BMI 18.5-35kg/m2.
Treated with once-daily insulin glargine for more than 3 months and with HbA1c ≤9.5% at screening.
Patients began a 6-week run-in period and were titrated with first reference insulin glargine and then insulin lispro, as needed, to ensure good diabetes control as determined by the investigator.
At randomization, there was a 1:1 (unit for unit) conversion of reference insulin glargine to SEMGLEE (100 U/mL of insulin glargine) and of prestudy mealtime insulin to insulin lispro.

Change in HbA1c from baseline to week 24 in all and insulin-naïve patients with SEMGLEETM and reference insulin glargine3

Mean change in fasting plasma glucose from baseline at week 24 and 52

SEMGLEE demonstrated non-inferior efficacy to the reference product in the treatment of hyperglycemia in patients with type 2 diabetes mellitus.

Conducted in patients with type 2 diabetes, a 24 weeks multicenter, open-label, randomized, active-controlled study evaluated the glucose lowering effect of once-daily SEMGLEE compared to that of once-daily administration of reference insulin glargine product, 100 units/mL, both administered in combination with oral antidiabetic drugs. Mean age was 55 years, more than half, 52.7%, of the patients were caucasian, 26.6% were hispanic, and 9.8% were black, mean BMI was 31.5 kg/m2, the mean duration of diabetes prior to entry into the study was 12 years, the mean exposure of 276 patients to SEMGLEE during the study was 22 weeks. At week 24, treatment with SEMGLEE was found to be non-inferior to the reference insulin glargine product with regard to the reduction in HbA1c over 24 weeks of treatment.

In the INSTRIDE 2 Trial, SEMGLEE demonstrated non-inferiority to the reference product in the treatment of hyperglycemia in adult patients with type 2 diabetes mellitus.3

INSTRIDE 2 TRIAL DESIGN3
Primary Endpoint: Based on change in HbA1c from baseline to week 24.
Secondary Endpoint: Included changes from baseline in basal insulin dose as well as fasting plasma glucose (FPG), SMBG and immunogenicity.
Multicentre, open-label, randomized, parallel group, 24-week trial.
560 patients with type 2 diabetes, 312 males and 248 females, aged 18-65 years,
BMI 18.5-40 kg/m2.
For the first 12-weeks, basal insulin was titrated without altering oral antidiabetic drug doses (the most common were metformin, 70.4%,; glimepirides 22.0%, glipizides 14.6% and metformin hydrochloride 11.1%). During the following 12 week maintenance period, all oral antidiabetic treatments were unchanged.
Change in HbA1c from baseline to week 24 in all and insulin naive patients with SEMGLEETM and reference insulin glargine3
Change in 7-point self-monitored blood glucose (SMBG) profile from baseline to week 24 in all and insulin-naive patients with SEMGLEE and reference insulin glargine.3

References:

  • SEMGLEE (insulin glargine injection). Prescribing Information. 2020. Mylan Pharmaceuticals Inc. Morgantown, WV. 
  • Blevins TC, Barve A, Sun B, Ankersen M. Efficacy and safety of MYL-1501D vs insulin glargine in patients with type 1 diabetes after 52 weeks: Results of the INSTRIDE 1 phase III study. Diabetes Obes Metab. 2018;20(8):1944‐1950.
  • Blevins TC, Barve A, Sun B, et al. Efficacy and safety of MYL-1501D versus insulin glargine in patients with type 2 diabetes after 24 weeks: Results of the phase III INSTRIDE 2 study. Diabetes Obes Metab. 2019;21(1):129‐135.

Adverse Events Reporting

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare providers are asked to report any suspected adverse reactions. Reporting forms and information can be found at http://www.mhra.gov.uk/yellowcard. In order to support effective tracking and traceability of biologics including biosimilars, it is recommended that the brand name and batch number are recorded and used when reporting adverse events. You can also report adverse events direct to the marketing authorisation holder at ukpharmacovigilance@mylan.com.

Semglee® (Insulin glargine) 100 units/ml solution for injection in pre-filled pen

Prescribing information

Please refer to Summary of Product Characteristics (SmPC) before prescribing.

Indication: Semglee® is indicated in the treatment of diabetes mellitus in adults, adolescents and children aged 2 years and above. Presentation: Each ml contains 100 units insulin glargine* (equivalent to 3.64 mg). Each pen contains 3 ml of solution for injection, equivalent to 300 units. Dosage and administration: Semglee® (insulin glargine) has a prolonged duration of action. It should be administered once daily at any time but at the same time each day. The pre filled pen delivers insulin in increments of 1 unit up to a maximum single dose of 80 units. The dose regimen (dose and timing) should be individually adjusted. In patients with type 2 diabetes mellitus, Semglee® can also be given together with orally active antidiabetic medicinal products. The potency of Semglee® is stated in units and these units are exclusive to Semglee®. Special population: Elderly population (≤ 65 years old): progressive deterioration of renal function may lead to a steady decrease in insulin requirements. Renal impairment: insulin requirements may be diminished due to reduced insulin metabolism. Hepatic impairment: insulin requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin metabolism. Paediatric population: For adolescents and children aged 2 years and older patients, the dose regimen (dose and timing) should be individually adjusted. For children below 2 years of age the safety and efficacy of Semglee® have not been established. No data are available. Switch from other insulins to Semglee® When switching from a treatment regimen with an intermediate or long acting insulin to a regimen with Semglee®, a change of the dose of the basal insulin may be required and the concomitant antidiabetic treatment may need to be adjusted (dose and timing of additional regular insulins or fast acting insulin analogues or the dose of oral antidiabetic medicinal products). Switch from twice daily NPH insulin to Semglee®: To reduce the risk of nocturnal and early morning hypoglycaemia, daily dose of once daily basal insulin should be reduced by 20-30% during the first weeks of treatment. Switch from insulin glargine 300 units/ml to Semglee®: Semglee® and insulin glargine 300 units/ml are not bioequivalent and are not directly interchangeable. To reduce the risk of hypoglycemia in this group, Semglee® dose should be reduced by approximately 20%. During the first weeks increase mealtime insulin, after this period the regimen should be adjusted individually. Close metabolic monitoring is recommended during the switch and in the initial weeks thereafter. A further adjustment in dose regimen may become necessary with improved metabolic control, change of timing of insulin, patient weight or life style changes. Patients with high insulin doses because of antibodies to human insulin may experience an improved insulin response with Semglee®. Method of administration Semglee® is administered subcutaneously only. Injection sites must be rotated within a given injection area from one injection to the next. Semglee® must not be mixed with any other insulin or diluted. Before using the pre filled pen, the instructions for use included in the package leaflet must be read carefully (see section 6.6). Contraindications: Known hypersensitivity to the active substances or to any of the excipients. Warnings and precautions: Warnings: Semglee® is not the insulin of choice for the treatment of diabetic ketoacidosis. In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must be reviewed before dose adjustment is considered. Changes in insulin strength, manufacturer, type, origin, method of manufacture and/or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant oral antidiabetic treatment. Hypoglycaemia Due to more sustained basal insulin supply with Semglee®, less nocturnal but more early morning hypoglycaemia can be expected. Intercurrent illness In many cases urine tests for ketones are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often increased. Patients with type 1 diabetes must continue to consume at least a small amount of carbohydrates on a regular basis, even if they are able to eat only little or no food or are vomiting etc. and they must never omit insulin entirely. Insulin antibodies Rare chance of antibodies formation, may require insulin dose adjustment to avoid hyper- or hypoglycaemia. Handling of the pen Before using Semglee® pen, the instructions for use included in the package leaflet must be read carefully. Semglee® pen has to be used as recommended in the instructions for use. Medication errors Insulin label must always be checked before each injection to avoid medication errors between insulin glargine and other insulins. Interaction with other medicinal products: Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs when used with Semglee®. Substances that may enhance the blood glucose lowering effect include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, propoxyphene, salicylates and sulfonamide antibiotics. Substances that may reduce the blood glucose lowering effect include corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens, phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine [adrenaline], salbutamol, terbutaline), thyroid hormones, atypical antipsychotic medicinal products (e.g. clozapine and olanzapine) and protease inhibitors. Beta blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood glucose lowering effect of insulin. Pentamidine may cause hypoglycaemia, which may sometimes be followed by hyperglycaemia. Pregnancy and lactation: Pregnancy For insulin glargine no clinical data on exposed pregnancies from controlled clinical studies are available. A large amount of data on pregnant women (more than 1000 pregnancy outcomes) indicate no specific adverse effects of insulin glargine on pregnancy and no specific malformative nor feto/neonatal toxicity of insulin glargine. Animal data do not indicate reproductive toxicity. The use of Semglee® may be considered during pregnancy, if clinically needed. The use of Semglee® may be considered during pregnancy, if clinically needed. Careful monitoring of glucose control is essential. Breast feeding It is unknown whether insulin glargine is excreted in human milk. Women may require adjustments in insulin dose and diet. Effects on ability to drive and use machines: The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for example, as a result of visual impairment. Undesirable effects: Very common: Hypoglycaemia. Common: Lipohypertrophy, Injection site reactions Uncommon: Lipoatrophy. For rare and very rare undesirable effects, please refer to SmPC. Name and Address of Marketing Authorisation Holder: Mylan S.A.S., 117 allée des Parcs, 69800 Saint Priest, France. Marketing Authorisation Number: EU/1/18/1270/003 Basic NHS price: 3ml x 5 pens=£29.99 Legal Category: POM Date of Last Revision: October 2018

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu. and from Mylan Medical Information, Building 4, Trident Place, Hatfield Business Park, Mosquito Way, Hatfield, Hertfordshire, AL10 9BW, phone no. 01707 853000, Email: info@mylan.co.uk

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare providers are asked to report any suspected adverse reactions. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. In order to support effective tracking and traceability of biologics including biosimilars, it is recommended that the brand name and batch number are recorded and used when reporting adverse events. Adverse events should be reported to Pharmacovigilance, Mylan, Building 4, Trident Place, Hatfield Business Park, Mosquito Way, Hatfield, Hertfordshire, AL10 9UL, on phone no. 0800 121 8267, Email: ukpharmacovigilance@mylan.com

MORE LESS
INDICATIONS AND USAGE

Semglee is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus (T1D) and in adults with type 2 diabetes mellitus (T2D).

Limitations of Use

Semglee is not recommended for the treatment of diabetic ketoacidosis.

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

WARNINGS AND PRECAUTIONS
Never Share a Semglee Prefilled Pen, Syringe or Needle Between Patients

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 or hyperglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring.

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

Hypoglycemia is the most common adverse reaction associated with insulin, including SEMGLEE and may be life-threatening.

Medication errors, such as accidental mix-ups between long-acting insulin products and other insulins, particularly rapid-acting insulins, have been reported. To avoid medication errors between SEMGLEE and other insulins, instruct patients to always check the insulin label before each injection.

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue SEMGLEE, treat and monitor until symptoms and signs resolve.

All insulin products, including SEMGLEE, 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.

Fluid retention, which may lead to or exacerbate heart failure can occur with concomitant use of thiazolidinediones (TZDs) with insulin. These patents should be observed for signs and symptoms of heart failure. If heart failure develops, dosage reduction or discontinuation of the TZD must be considered. 

Do not dilute or mix SEMGLEE with any other insulin or solution. If mixed or diluted, the solution may become cloudy, and the onset of action/time to peak effect may be altered in an unpredictable manner. Do not administer SEMGLEE via an insulin pump or intravenously because hypoglycemia can occur.

A reduction in the SEMGLEE dose may be required in patients with renal or hepatic impairment.

DRUG INTERACTIONS
Certain drugs may affect glucose metabolism, requiring insulin dose adjustment and close monitoring of blood glucose. The signs hypoglycemia may be reduced in patients taking anti-adrenergic drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine). 

ADVERSE REACTIONS
Adverse reactions commonly associated with SEMGLEE include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritis, rash, edema and weight gain.