6.1 Drugs used in diabetes

6.1.1 Insulins

General Notes
For further guidance please refer to the NHS Lothian paediatric diabetes handbook, SIGN guideline 116: Management of Diabetes and NICE guideline 18: Diabetes (type 1 and type 2) in children and young people; diagnosis and management

Insulin should be initiated on specialist advice only. Whatever insulin regimen is chosen it must be supported by comprehensive education appropriate for the age, maturity and individual needs of the child and family.

Insulin choices - specialist initiation only

 

Rapid

5-15 minutes before food

Or

CSII

Short

15-30 mins before food

Long acting Basal analogues

Same time every day

Intermediate

isophane insulin

Same time every day

Biphasic insulin analogue

Up to 15mins before food
Biphasic isophane insulin

Up to 30mins before food
First choice Novorapid® Actrapid® Levemir® Insulatard® Humalog Mix 25® Humulin M3®
Alternate choice Humalog® Apidra®


Humulin S® *insulin glargine Humulin I® Humalog Mix 50®
Novomix 30®

CSII - continuous subcutaneous insulin infusion or insulin pumps
* Insulin Glargine is available as different branded products. it is important that these are prescribed by brand name to ensure the patient receives the intended product. Brands include Lantus 100units/mL and Abasaglar 100units/mL (biosimilar). Toujeo is non-formulary and should not be prescribed, it is not a bioequivalent for other insulin glargines. There is a safety issue if doses are swapped on a unit per unit basis. 
Prescribing Notes
  • Type of insulin, device and needle size should be specified. Care should be taken to write the brand name in full to avoid errors.
  • The majority of children and young people use 4mm length needles; due to individual patient variability other needle sizes may be prescribed.

  • Patients should not be changed from the insulin that they are currently receiving without specialist advice.
  • Prepubertal children [outside the partial remission phase] usually require 0.7 – 0.9 units of insulin/kg/day. During puberty, requirements may rise to 1.3 units of insulin/kg/day.
  • The B–D Safe–Clip device snaps the needle off insulin syringes and stores the needle safely inside the clipper; this device is available on prescription. Sharps containers are available on prescription, as listed in Part 3 [appliances] of the Scottish Drug Tariff.
  • Insulin is available in 3mL cartridges, 10mL vials and 3mL disposable pens.  The majority of paediatric patients are prescribed 3mL cartridges to be used with pen devices.  Pen devices include half unit pens and unit pens.  For patients on pen devices with cartridges care should be taken to ensure that compatible cartridges are prescribed.
  • Patients on continuous subcutaneous insulin infusion (CSII, insulin pumps) will normally be prescribed 10mL insulin vials.  Selected pump devices use prefilled pump cartidges - details will be highlighted in individual patient correspondence.
  • Levemir is the basal analogue insulin of choice in younger paediatric patients. Insulin glargine may be used in older patients.
6.1.2 Oral drug therapy for non-type 1 diabetes and insulin resistance
General Notes
For further guidance please refer to NICE guideline 18: Diabetes (type 1 and type 2) in children and young people; diagnosis and management and the International Society for Paediatric and Adolescent Diabetes (ISPAD) Clinical practice consensus guidelines 2014. Type 2 diabetes in the child and adolescent. Metformin is the first choice oral agent for children with type 2 diabetes. Patients with type 2 diabetes who cannot be managed on metformin and/or sulpohylureas will be discussed with adult diabetes services.

Seek specialist advice for the managenemt of type 2 diabetes and MODY (Maturity Onset Diabetes of the Young) in children. Further information can be found on the Diabetes Genes website.

(a) biguanides

Specialist use only
 First Choices:
metformin
Formulations/Dose
  • metformin tablets 500mg, 850mg; 500mg/5mL oral solution
    • Child 8-9 years, initially 200mg once daily, dose to be adjusted according to response at intervals of at least 1 week, maximum daily dose to be given in 2-3 divided doses; maximum 2g per day.
    • Child 10-17 years, initially 500mg once daily, dose to be adjusted according to response at intervals of at least 1 week, maximum daily dose to be given in 2-3 divided doses; maximum 2g per day.
Prescribing Notes
  • Give metformin with or just after food, or a meal.
  • Metformin causes gastro–intestinal adverse effects; it should be started at low dose and taken with meals, and the dose increased if tolerated.
  • Due to the serious risk of lactic acidosis, metformin should be avoided in significant renal impairment, severe cardiac/respiratory disease producing tissue hypoxia, and severe liver disease with potential for hepatic failure.
  • Hypoglycaemia does not usually occur with metformin.
  • Those with type 2 diabetes may require treatment with insulin, in combination with oral agents.
  • Oral solution should be reserved for patients who are unable to swallow tablets.

(b) sulphonylureas

Specialist use only

First Choice:
gliclazide
Second Choice:
glibenclamide
Formulations/Dose
  • gliclazide tablets 40mg, 80mg
    • Child 12-17 years, initially 20mg once daily, adjusted according to response, increased if necessary up to 160mg once daily (max. per dose 160mg twice daily) dose to be taken with breakfast.
  • glibenclamide tablets 2.5mg, 5mg
    • Child 12-17 years, initially 2.5mg daily, adjusted according to response, dose to be taken with or immediately after breakfast; maximum 15mg per day.
Prescribing Notes
  • Those with type 2 diabetes may require treatment with insulin, in combination with oral agents.
6.1.4 Treatment of hypoglycaemia in known diabetes and persistent hyperinsulinaemic hypoglycaemia of infancy
(a) treatment of hypglycaemia in known diabetes

Choice of treatment depends on the clinical situation and includes:
 
glucose (oral)
glucagon injection
glucose intravenous infusion 10%
Formulations/Dose
  • glucose (oral) oral gel 400mg/1g; powder; tablets (approx 3g per tablet)
    • initially 10-20g given orally (10g of fast acting glucose for oral administration is the equivalent of  - 3 glucose tablets or 2 teaspoons glucose powder in 10-20mls water/sugar free juice or 1 x 25g tube of oral gel 400mg/1g).   Alternatively 10-20g of fast acting glucose is the equivalent of a glass of non-diet soft drink or pure fruit juice.  The carbohydrate content of some soft drinks are subject to change at present, check individual product levels for glucose content and adjust the volume accordingly.
  • glucose intravenous infusion 10% (containing 100mg glucose per mL)
    • for children of all ages, administered by trained personnel, by slow intravenous bolus injection over several minutes, 200–400mg/kg (2-4mL/kg).
  • glucagon 1mg vial
    • Child 1 month - 1 year by subcutaneous or intramuscular injection 500micrograms
    • Child 2- 17 years (body weight up to 25kg) by subcutaneous or intramuscular injection, 500micrograms, if no response within 10 minutes intravenous glucose must be given
    • Child 2-17 years (body weight 25kg and above) by subcutaneous or intramuscular injection 1mg, if no response within 10 minutes intravenous glucose must be given.
Prescribing Notes
  • For further guidance please refer to the NHS Lothian paediatric diabetes handbook section on hypoglycaemia.
  • Following administration of glucagon, it is important to give supplementary carbohydrate to restore liver glycogen and prevent secondary hypoglycaemia.
  • Glucose 20% or 50% intravenous infusion should not be used to treat hypoglycaemia in children.
  • Although intravenous glucose is the more effective treatment where intravenous access is readily available, intramuscular glucagon may be more appropriate.
  • Following administration of glucagon, the patient should attend hospital for immediate review.
(b) treatment of persistent hyperinsulinaemic hypoglycaemia of infancy

First Choice:
diazoxide
+chlorothiazide
Dose
  • diazoxide tablets 50mg; oral liquid 250mg/5mL[unlicensed preparation]
    • Neonate, initially 5mg/kg twice daily, adjusted according to response, initial dose used to establish response; maintenance 1.5-3mg/kg 2-3 times a day; increased if necessary up to 7mg/kg 3 times a day, higher doses are unlikely to be beneficial, but may be required in some cases.
    • Child, initially 1.7mg/kg 3 times a day, adjusted according to response; maintenance 1.5-3mg/kg 2-3 times a day, increased if necessary up to 5mg/kg 3 times a day, doses up to 5mg/kg may be required in some cases, but higher doses are unlikely to be beneficial.
  • chlorothiazide tablets 250mg; oral liquid 250mg/5mL[unlicensed preparation]
    • Child, 3-5mg/kg twice daily.
Prescribing Notes
  • Side–effects from diazoxide include fluid retention, hypertrichosis, facial changes, hypotension, rarely leucopenia, thrombocytopenia.
  • Haematological and blood pressure monitoring are required during prolonged treatment.
  • Chlorothiazide acts synergistically with diazoxide. They should normally be used in combination.
  • Patients who fail to respond to the above treatment will be discussed with national specialist centres.  Other treatment options include glucagon, octreotide injection or infusion.
6.1.6 Glucose monitoring agents in diabetes mellitus
Regular monitoring is crucial in type 1 diabetes, patients are recommended to check their blood glucose either 4 or 8 times per day (sometimes more often), refer to the Paediatrics Diabetes Handbook - day-to-day management for more details. Choice of meter depends on experience and patient preference and capabilities e.g. visual acuity, manual dexterity. Patients should be discouraged from purchasing their own meter, and should do so only following expert advice from a suitably trained person. 
(a) capillary blood glucose monitoring

First Choices:
Performa
      Compatible meter
      Accucheck Performa Nano
Second Choices:
as advised by the paediatric diabetes team
Prescribing Notes
  • The paediatric diabetes team will provide blood glucose meters to patients with type 1 and type 2 diabetes.  Some patients may require a specialist meter taking into account individual factors following assessment by the paediatric diabetes team.  The appropriate testing strips to be prescribed will be detailed in individual patient correspondence.
  • The specialist paediatric diabetes team recommends home blood glucose monitoring in all children and young people with type 2 diabetes in order to reduce the risk of long-term complications by achieving a target HbA1c of less than 48mmol/mol.  The timing of samples will be tailored to the individual patient and education will be provided by the paediatric diabetes team.

  • Accu-check Mobile is alternative meter choice in selected older children.
  • Correct meter care and quality control are essential when meters are used.
  • Patients must be aware of how to interpret the results.
  • Meters are obtainable from centres with expert advice from a suitably trained person.
  • Strips deteriorate rapidly if exposed to the atmosphere.
(b) capillary blood ketone monitoring

First choice:
Freestyle Optium B-ketone     
Compatible meter

     Freestyle Optium
     Freestyle Optium Neo

Second Choice:
Glucomen LX Ketone
Compatible meter
     Glucomen LX Plus
Prescribing Notes
  • Meters are supplied with expert advice from the paediatric diabetes service.
  • It is important to test for blood ketones where there is a significant risk of diabetic ketoacidosis, such as people with type 1 diabetes with intercurrent illness and when using insulin pump therapy.
  • Patients must be aware of when to test and how to interpret the results.
  • Blood ketone testing is the most accurate form of testing.