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 50mls original Lucozade® or 1 x 25g tube of oral gel 400mg/1g).
  • 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. 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. Strips may be prescribed and can also be bought over-the-counter.
(a) capillary blood glucose monitoring

First Choices:
Accu-Chek ® Compact
Accu-Chek ® Advantage
One Touch ® Ultra®
One Touch ® Ultra Smart®
Optium Xceed ® (for use with Optium® Plus
test strips or MediSense® Optium® β-Ketone test strips)
Second Choices:
FreeStyle ® Mini
Ascensia Contour ®
Prescribing Notes
  • Home blood glucose monitoring need not be performed by:

    • those treated by diet alone where HbA1c is <6.5%
    • those who are well controlled on metformin and/or glitazone and stable as indicated by HbA1c <7%.

    In these cases, a six-monthly estimate of HbA1c is adequate to monitor glycaemic control.

  • Home blood glucose monitoring in non–insulin treated Type 2 diabetes and steroid-induced diabetes should routinely be undertaken:

    • where control is poor
    • where treatment change is indicated especially where there is a risk of hypoglycaemia
    • to monitor a treatment change
    • in patients on sulphonylureas with symptoms which may be due to unrecognized hypoglycaemia

    In such cases, blood glucose monitoring should not require to be performed routinely on more than 2 days in the week or more than twice in the day although in some cases more frequent testing may be required. The timing of the samples will depend on the particular case but a fasting value is useful. 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) urine testing for ketones

 
Ketostix ®
Prescribing Notes
  • Meters are obtainable from centres with expert advice from a suitably trained person; it is impossible to recommend one specific meter since they are all similar in quality and cost.
  • The rationale for monitoring should be tailored to the individual.
  • It is important to test for ketones where there is a significant risk of ketoacidosis, such as may occur with any intercurrent illness, and high blood glucose level (>15 mmol/L).