patient, especially when concomitant glucose-lowering
Driving and skilled tasks Drivers need to be particularly
careful to avoid hypoglycaemia and should be warned of
▶ Adult: Initially 5 mg daily, adjusted according to
response, dose to be taken with or immediately after
breakfast; maximum 15 mg per day
l UNLICENSED USE Not licensed for use in breast feeding
women with pre-existing diabetes. Not licensed for use in
l CONTRA-INDICATIONS Avoid where possible in Acute
l INTERACTIONS → Appendix 1: sulfonylureas
l SIDE-EFFECTS Appetite decreased . gastrointestinal
discomfort. SIADH .taste metallic
l PREGNANCY The use of sulfonylureas in pregnancy should
generally be avoided because of the risk of neonatal
hypoglycaemia; however, glibenclamide can be used
during the second and third trimesters of pregnancy in
women with gestational diabetes.
l BREAST FEEDING Glibenclamide can be used during
breast-feeding in women with pre-existing diabetes.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
▶ Glibenclamide (Non-proprietary)
Glibenclamide 2.5 mg Glibenclamide 2.5mg tablets | 28 tablet P £14.33 DT = £13.76
Glibenclamide 5 mg Glibenclamide 5mg tablets | 28 tablet P £14.72 DT = £3.76
▶ BY MOUTH USING IMMEDIATE-RELEASE MEDICINES
▶ Adult: Initially 40–80 mg daily, adjusted according to
response, increased if necessary up to 160 mg once
daily, dose to be taken with breakfast, doses higher
than 160 mg to be given in divided doses; maximum
▶ BY MOUTH USING MODIFIED-RELEASE MEDICINES
▶ Adult: Initially 30 mg daily, dose to be taken with
breakfast, adjust dose according to response every
4 weeks (after 2 weeks if no decrease in blood glucose);
DOSE EQUIVALENCE AND CONVERSION
▶ Gliclazide modified release 30 mg may be considered to
be approximately equivalent in therapeutic effect to
standard formulation gliclazide 80 mg.
l CONTRA-INDICATIONS Avoid where possible in Acute
l INTERACTIONS → Appendix 1: sulfonylureas
l PREGNANCY The use of sulfonylureas in pregnancy should
generally be avoided because of the risk of neonatal
l BREAST FEEDING Avoid—theoretical possibility of
l RENAL IMPAIRMENT If necessary, gliclazide which is
principally metabolised in the liver, can be used in renal
impairment but careful monitoring of blood-glucose
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension
CAUTIONARY AND ADVISORY LABELS 25
Gliclazide 30 mg Dacadis MR 30mg tablets | 28 tablet P £2.81
DT = £2.81 | 56 tablet P £5.62
▶ Diamicron MR (Servier Laboratories Ltd)
Gliclazide 30 mg Diamicron 30mg MR tablets | 28 tablet P £2.81 DT = £2.81 | 56 tablet P £5.62
Gliclazide 30 mg Edicil MR 30mg tablets | 28 tablet P £2.62 DT
▶ Laaglyda MR (Consilient Health Ltd)
Gliclazide 60 mg Laaglyda MR 60mg tablets | 28 tablet P £4.77
▶ Nazdol MR (Consilient Health Ltd)
Gliclazide 30 mg Nazdol MR 30mg tablets | 28 tablet P £2.35 DT
Gliclazide 60 mg Vamju 60mg modified-release tablets | 28 tablet P £3.28 DT = £4.77
▶ Ziclaseg (Lupin Healthcare (UK) Ltd)
▶ Zicron PR (Bristol Laboratories Ltd)
Gliclazide 30 mg Zicron PR 30mg tablets | 28 tablet P £1.95 DT
▶ Gliclazide (Non-proprietary)
Gliclazide 40 mg Gliclazide 40mg tablets | 28 tablet P £0.75–
Gliclazide 80 mg Gliclazide 80mg tablets | 28 tablet P £1.37 DT
= £0.82 | 60 tablet P £0.81–£1.80
▶ Diamicron (Servier Laboratories Ltd)
Gliclazide 80 mg Diamicron 80mg tablets | 60 tablet P £4.38
Gliclazide 160 mg Glydex 160mg tablets | 28 tablet P £1.79
▶ Zicron (Bristol Laboratories Ltd)
Gliclazide 40 mg Zicron 40mg tablets | 28 tablet P £3.36 DT =
▶ Adult: Initially 1 mg daily, adjusted according to
response, then increased in steps of 1 mg every
1–2 weeks, increased to 4 mg daily, dose to be taken
shortly before or with first main meal, the daily dose
may be increased further, in exceptional
circumstances; maximum 6 mg per day
▶ Porphyria Sulfonylureas should be avoided where possible
in Acute porphyrias p. 1058 but glimepiride is thought to
l INTERACTIONS → Appendix 1: sulfonylureas
▶ Rare or very rare Gastrointestinal discomfort. hypersensitivity vasculitis
▶ Frequency not known Drug cross-reactivity .rash
l PREGNANCY The use of sulfonylureas in pregnancy should
generally be avoided because of the risk of neonatal
l BREAST FEEDING Avoid—theoretical possibility of
l MONITORING REQUIREMENTS Manufacturer recommends
regular hepatic and haematological monitoring but limited
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
▶ Glimepiride (Non-proprietary)
Glimepiride 1 mg Glimepiride 1mg tablets | 30 tablet P £5.00
Glimepiride 2 mg Glimepiride 2mg tablets | 30 tablet P £7.13
Glimepiride 3 mg Glimepiride 3mg tablets | 30 tablet P £10.75
Glimepiride 4 mg Glimepiride 4mg tablets | 30 tablet P £14.24
Glimepiride 3 mg Amaryl 3mg tablets | 30 tablet P £10.75 DT =
▶ Adult: Initially 2.5–5 mg daily, adjusted according to
response, dose to be taken shortly before breakfast or
lunch, doses up to 15 mg may be given as a single dose,
higher doses to be given in divided doses; maximum
▶ Porphyria Sulfonylureas should be avoided where possible
in Acute porphyrias p. 1058 but glipizide is thought to be
l INTERACTIONS → Appendix 1: sulfonylureas
▶ Common or very common Abdominal pain upper
▶ Uncommon Dizziness . drowsiness . skin reactions .tremor . vision disorders
▶ Frequency not known Confusion . headache . hyponatraemia . malaise . photosensitivity reaction
l PREGNANCY The use of sulfonylureas in pregnancy should
generally be avoided because of the risk of neonatal
l BREAST FEEDING Avoid—theoretical possibility of
l HEPATIC IMPAIRMENT Avoid if the patient has both renal
l RENAL IMPAIRMENT Avoid if the patient has both renal
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Glipizide 5 mg Glipizide 5mg tablets | 28 tablet P £3.00 DT =
£2.60 | 56 tablet P £5.20–£6.00
Glipizide 5 mg Minodiab 5mg tablets | 28 tablet P £1.26 DT =
▶ Adult: 0.5–1.5 g daily in divided doses, dose to be taken
with or immediately after meals, alternatively 0.5–1.5 g
once daily, dose to be taken with or immediately after
breakfast; maximum 2 g per day
l CONTRA-INDICATIONS Avoid where possible in Acute
l INTERACTIONS → Appendix 1: sulfonylureas
▶ Rare or very rare Aplastic anaemia . blood disorder
▶ Frequency not known Alcohol intolerance . appetite
abnormal . erythema multiforme (usually in the first
6–8 weeks of therapy). exfoliative dermatitis (usually in
the first 6–8 weeks of therapy). fever (usually in the first
6–8 weeks of therapy). headache . hypersensitivity
l PREGNANCY The use of sulfonylureas in pregnancy should
generally be avoided because of the risk of neonatal
possibility of hypoglycaemia in the infant.
l RENAL IMPAIRMENT If necessary, the short-acting drug
tolbutamide can be used in renal impairment but careful
monitoring of blood-glucose concentration is essential.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension
▶ Tolbutamide (Non-proprietary)
Tolbutamide 500 mg Tolbutamide 500mg tablets | 28 tablet P £34.88 DT = £3.74 | 112 tablet P £14.96
BLOOD GLUCOSE LOWERING DRUGS ›
l DRUG ACTION The thiazolidinedione, pioglitazone,
reduces peripheral insulin resistance, leading to a
reduction of blood-glucose concentration.
Type 2 diabetes mellitus (alone or combined with
metformin or a sulfonylurea, or with both, or with
▶ Adult: Initially 15–30 mg once daily, adjusted
according to response to 45 mg once daily, in elderly
patients, initiate with lowest possible dose and
increase gradually; review treatment after 3–6 months
710 Diabetes mellitus and hypoglycaemia BNF 78
DOSE ADJUSTMENTS DUE TO INTERACTIONS
▶ Dose of concomitant sulfonylurea or insulin may need
MHRA/CHM ADVICE: PIOGLITAZONE CARDIOVASCULAR SAFETY
(DECEMBER 2007 AND JANUARY 2011)
Incidence of heart failure is increased when pioglitazone
is combined with insulin especially in patients with
predisposing factors e.g. previous myocardial infarction.
Patients who take pioglitazone should be closely
monitored for signs of heart failure; treatment should be
discontinued if any deterioration in cardiac status
Pioglitazone should not be used in patients with heart
failure or a history of heart failure.
PIOGLITAZONE: RISK OF BLADDER CANCER (JULY 2011)
The European Medicines Agency has advised that there
is a small increased risk of bladder cancer associated with
pioglitazone use. However, in patients who respond
adequately to treatment, the benefits of pioglitazone
continue to outweigh the risks.
Pioglitazone should not be used in patients with active
bladder cancer or a past history of bladder cancer, or in
those who have uninvestigated macroscopic haematuria.
Pioglitazone should be used with caution in elderly
patients as the risk of bladder cancer increases with age.
Before initiating treatment with pioglitazone, patients
should be assessed for risk factors of bladder cancer
(including age, smoking status, exposure to certain
occupational or chemotherapy agents, or previous
radiation therapy to the pelvic region) and any
macroscopic haematuria should be investigated. The
safety and efficacy of pioglitazone should be reviewed
after 3–6 months and pioglitazone should be stopped in
patients who do not respond adequately to treatment.
Patients already receiving treatment with pioglitazone
should be assessed for risk factors of bladder cancer and
treatment should be reviewed after 3–6 months, as
Patients should be advised to report promptly any
haematuria, dysuria, or urinary urgency during
l CONTRA-INDICATIONS History of heart failure . previous or
active bladder cancer. uninvestigated macroscopic
l CAUTIONS Cardiovascular disease or in combination with
insulin (risk of heart failure) . elderly (increased risk of
heart failure, fractures, and bladder cancer). increased risk
of bone fractures, particularly in women .risk factors for
CAUTIONS, FURTHER INFORMATION Substitute insulin
l INTERACTIONS → Appendix 1: pioglitazone
▶ Common or very common Bone fracture . increased risk of
infection . numbness . visual impairment. weight
▶ Uncommon Bladder cancer. insomnia
▶ Frequency not known Macular oedema
SIDE-EFFECTS, FURTHER INFORMATION Rare reports of liver
dysfunction; discontinue if jaundice occurs.
l PREGNANCY Avoid—toxicity in animal studies.
l BREAST FEEDING Avoid—present in milk in animal studies.
l HEPATIC IMPAIRMENT Manufacturer advises avoid.
l MONITORING REQUIREMENTS Monitor liver function
before treatment and periodically thereafter.
Liver toxicity Patients should be advised to seek immediate
medical attention if symptoms such as nausea, vomiting,
abdominal pain, fatigue and dark urine develop.
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium accepts use of
pioglitazone (February 2007) with metformin and a
sulfonylurea, for patients (especially if overweight) whose
glycaemic control is inadequate despite the use of 2 oral
hypoglycaemic drugs and who are unable or unwilling to
take insulin; treatment should be initiated and monitored
by an experienced diabetes physician.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension
▶ Pioglitazone (Non-proprietary)
Pioglitazone (as Pioglitazone hydrochloride) 15 mg Pioglitazone
15mg tablets | 28 tablet P £25.83 DT = £1.45
Pioglitazone (as Pioglitazone hydrochloride) 30 mg Pioglitazone
30mg tablets | 28 tablet P £35.89 DT = £2.02
Pioglitazone (as Pioglitazone hydrochloride) 45 mg Pioglitazone
45mg tablets | 28 tablet P £39.55 DT = £2.15
Pioglitazone (as Pioglitazone hydrochloride) 15 mg Actos 15mg
tablets | 28 tablet P £25.83 DT = £1.45
Pioglitazone (as Pioglitazone hydrochloride) 30 mg Actos 30mg
tablets | 28 tablet P £35.89 DT = £2.02
Pioglitazone (as Pioglitazone hydrochloride) 45 mg Actos 45mg
tablets | 28 tablet P £39.55 DT = £2.15
Pioglitazone (as Pioglitazone hydrochloride) 15 mg Glidipion
15mg tablets | 28 tablet P £25.83 DT = £1.45
Pioglitazone (as Pioglitazone hydrochloride) 30 mg Glidipion
30mg tablets | 28 tablet P £35.89 DT = £2.02
Pioglitazone (as Pioglitazone hydrochloride) 45 mg Glidipion
45mg tablets | 28 tablet P £39.55 DT = £2.15
The properties listed below are those particular to the
combination only. For the properties of the components
please consider, pioglitazone p. 710, metformin
Type 2 diabetes not controlled by metformin alone
▶ Adult: 1 tablet twice daily, titration with the individual
components (pioglitazone and metformin) desirable
l INTERACTIONS → Appendix 1: metformin . pioglitazone
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 21
▶ Pioglitazone with metformin (Non-proprietary)
Pioglitazone (as Pioglitazone hydrochloride) 15 mg, Metformin
hydrochloride 850 mg Pioglitazone 15mg / Metformin 850mg
tablets | 56 tablet P £34.10 DT = £31.94
Pioglitazone (as Pioglitazone hydrochloride) 15 mg, Metformin
hydrochloride 850 mg Competact 15mg/850mg tablets | 56 tablet P £35.89 DT = £31.94
NHS IMPROVEMENT PATIENT SAFETY ALERT: RISK OF SEVERE
HARM AND DEATH DUE TO WITHDRAWING INSULIN FROM PEN
Insulin should not be extracted from insulin pen devices.
The strength of insulin in pen devices can vary by
multiples of 100 units/mL. Insulin syringes have
graduations only suitable for calculating doses of
standard 100 units/mL. If insulin extracted from a pen or
cartridge is of a higher strength, and that is not
considered in determining the volume required, it can
lead to a significant and potentially fatal overdose.
▶ Common or very common Oedema
SIDE-EFFECTS, FURTHER INFORMATION
Overdose Overdose causes hypoglycaemia.
Dose adjustments During pregnancy, insulin requirements
may alter and doses should be assessed frequently by an
experienced diabetes physician.
The dose of insulin generally needs to be increased in
the second and third trimesters of pregnancy.
Dose adjustments During breast-feeding, insulin
requirements may alter and doses should be assessed
frequently by an experienced diabetes physician.
Dose adjustments Insulin requirements may be decreased
in patients with hepatic impairment.
l RENAL IMPAIRMENT The compensatory response to
hypoglycaemia is impaired in renal impairment.
Dose adjustments Insulin requirements may decrease in
patients with renal impairment and therefore dose
▶ Many patients now monitor their own blood-glucose
concentrations; all carers and children need to be trained
▶ Since blood-glucose concentration varies substantially
throughout the day, ‘normoglycaemia’ cannot always be
achieved throughout a 24-hour period without causing
▶ In adults It is therefore best to recommend that patients
should maintain a blood-glucose concentration of between
4 and 9 mmol/litre for most of the time (4–7 mmol/litre
before meals and less than 9 mmol/litre after meals).
▶ In children It is therefore best to recommend that children
should maintain a blood-glucose concentration of between
4 and 10 mmol/litre for most of the time (4–8 mmol/litre
before meals and less than 10 mmol/litre after meals).
While accepting that on occasions, for brief periods, the
blood-glucose concentration will be above these values;
strenuous efforts should be made to prevent it from falling
below 4 mmol/litre. Patients using multiple injection
regimens should understand how to adjust their insulin
regulated, and should be distributed throughout the day to
match the insulin regimen. The intake of energy and of
simple and complex carbohydrates should be adequate to
allow normal growth and development but obesity must be
l DIRECTIONS FOR ADMINISTRATION Insulin is generally
given by subcutaneous injection; the injection site should
be rotated to prevent lipodystrophy. Injection devices
(‘pens’), which hold the insulin in a cartridge and meter
the required dose, are convenient to use. Insulin syringes
(for use with needles) are required for insulins not
available in cartridge form, but are less popular with
children and carers. For intensive insulin regimens
multiple subcutaneous injections (3 or more times daily)
l PRESCRIBING AND DISPENSING INFORMATION Show
container to patient or carer and confirm the expected
Units The word ’unit’ should not be abbreviated.
Hypoglycaemia Hypoglycaemia is a potential problem with
insulin therapy. All patients must be carefully instructed
on how to avoid it; this involves appropriate adjustment of
insulin type, dose and frequency together with suitable
timing and quantity of meals and snacks.
Insulin Passport Insulin Passports and patient information
booklets should be offered to patients receiving insulin.
The Insulin Passport provides a record of the patient’s
current insulin preparations and contains a section for
emergency information. The patient information booklet
provides advice on the safe use of insulin. They are
3M Security Print and Systems Limited
GP practices can obtain supplies through their Local
NHS Trusts can order supplies from www.nhsforms.co.uk/
or by emailing nhsforms@mmm.com. Further information
is available at www.npsa.nhs.uk.
Driving and skilled tasks Drivers need to be particularly
careful to avoid hypoglycaemia and should be warned of
(Insulin Injection; Neutral Insulin; Soluble Insulin—
▶ BY SUBCUTANEOUS INJECTION, OR BY INTRAMUSCULAR
INJECTION, OR BY INTRAVENOUS INJECTION, OR BY
▶ Adult: According to requirements
Diabetic ketoacidosis | Diabetes during surgery
▶ Adult: (consult local protocol)
l INTERACTIONS → Appendix 1: insulins
▶ Rare or very rare Refraction disorder
l DIRECTIONS FOR ADMINISTRATION Short-acting injectable
insulins can be given by continuous subcutaneous infusion
using a portable infusion pump. This device delivers a
continuous basal insulin infusion and patient-activated
bolus doses at meal times. This technique can be useful for
patients who suffer recurrent hypoglycaemia or marked
morning rise in blood-glucose concentration despite
optimised multiple-injection regimens. Patients on
subcutaneous insulin infusion must be highly motivated,
able to monitor their blood-glucose concentration, and
have expert training, advice and supervision from an
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