Download Pharmacological Management of Type 2 Diabetes (excluding insulin

Pharmacological Management of Type 2 Diabetes (excluding insulin)
These recommendations relate to glucose control where control is inadequate from lifestyle
interventions
Antidiabetic Drugs of Choice
Concordance should always be determined before adding in additional drugs
Class
1. Biguanide
Formulary Choices
Metformin
Ist line: immediate release
-500mg daily and gradually titrated
to 2g per day in divided doses (or
3g per day under specialist
supervision)
2nd line: modified release
-initially 500mg OD, increased
every 10-15 days, max 2g OD with
evening meal
Metformin oral powder-reserved for
patients who cannot swallow the
solid dosage form
2. Sulfonylureas
Ist line: gliclazide
-40-80mg daily, up to 160mg as a
single dose, max 320mg daily
2nd line: gliclazide modified
release
-30mg daily, max 120mg daily
3. Acarbose
Acarbose
-50mg daily, increased to 50mg
TDS, then increased if needed
after 6-8 weeks to 100mg TDS,
Comments/Notes
-Metformin is the first line treatment for patients
with type 2 diabetes
-To minimise GI side effects, increase dose
gradually over weeks and ensure tablets are
taken with meals
-Modified release: reserved for those who
suffer with persistent GI side effects only after
gradual titration with immediate release
metformin
-If oral powder is not suitable because of
volume of liquid to be administered, a licensed
oral solution is available (500mg/5ml).
Unlicensed liquid ‘specials’ should be avoided.
-Caution in renal impairment. NICE
recommends that the dose should be reviewed
if serum creatinine exceeds 130 micromol/L or
eGFR is less than 45 ml/minute/1.73m2.
Stop metformin if the serum creatinine exceeds
150 micromol/L or eGFR is less than 30
ml/minute/1.73m2.
-Note that metformin has been associated with
a significant reduction in MI and stroke rates in
patients with type 2 diabetes as well as a
significant reduction in mortality.
-Consider as a first line option for patients who
are not overweight. Use in combination with
metformin, or use instead of metformin if not
tolerated or contraindicated, or use with other
agents. Add to metformin if blood glucose
control remains or becomes inadequate.
-Start at low dose. Maximum dosage should be
avoided particularly in combination with other
glucose lowering medication
-Modified release-only for patients with hectic
lifestyle to improve compliance
-Avoid glibenclamide-long acting and greater
risk of hypoglycaemia
-Consider when other glucose-lowering
medications are contra-indicated or not
tolerated
-Titrate dose slowly to reduce incidence of GI
Date approved: November 2013
Approved by: Medicines Management Committee
Review date: November 2014, or earlier as appropriate
1
max 200mg TDS
adverse effects
4. Rapid-acting
1st line: repaglinide
-Consider in those with an erratic lifestyle,
insulin
-500mcg 30 minutes before main
when lifestyle limits the use of sulfonylurea
secretagogues meal, increased up to four times
daily (30 minutes before food),
individual doses can be increased
to max 4mg as a single dose, max
total dose is 16mg daily
5. Glitazones
-Prescribing of pioglitazone should be in line with MHRA/CHM advice (cardiovascular
(thiazolidinedi safety, December 2007 and January 2011, and risk of bladder cancer July 2011)
ones)
-Pioglitazone should not be used in patients with heart failure or a history of heart
failure
-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
-Pioglitazone should not be used in people who are at higher risk of fracture
Pioglitazone-specialist
-May be preferable if the person has marked
recommendation
insulin insensitivity
-15-45mg OD
-NICE recommend to continue only if there is a
reduction ≥ 0.5% points in HbA1c in 6 months
(between 5 and 6 mmol/mol). However, because
of its potential long term adverse effects
consider continuing long term treatment only in
those with robust responses (> 11mmol/mol,
>1% points in HbA1c) particularly where other
treatments have proven ineffective.
Please consider the use of metformin or a sulfonylurea where appropriate prior to the use of a DPP4
inhibitor, SGLT2 inhibitor or GLP-1 receptor agonist
6. DPP4
Ist line: saxagliptin
-Consider saxagliptin instead of a sulfonylurea
inhibitors-5mg OD
as second line therapy when control of blood
gliptins
glucose remains or becomes inadequate and
2nd line: linagliptin (only if patient person is at significant risk of hypoglycaemia or
has renal impairment)
sulfonylurea not tolerated or contraindicated
-5mg OD
-Consider adding saxagliptin to sulfonylurea as
second-line therapy when control of blood
Non-formulary: sitagliptin,
glucose remains or becomes inadequate and
metformin not tolerated or contraindicated
vildagliptin
-Consider adding saxagliptin to metformin and a
sulfonylurea when control of blood glucose
remains or becomes inadequate
-Continue gliptin only if there is a reduction of
≥0.5% points in HbA1c in 6 months (between 5
and 6 mmol/mol)
-Saxagliptin: Reduce dose to 2.5mg OD in
moderate to severe renal impairment (caution in
patients with severe renal impairment (consider
use of linagliptin in these circumstances)
-Linagliptin: No dose adjustment required in
renal impairment
-Dose of concomitant sulfonylurea or insulin may
need to be reduced.
Date approved: November 2013
Approved by: Medicines Management Committee
Review date: November 2014, or earlier as appropriate
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7. SGLT2
inhibitor
Dapagliflozin
-10mg OD
8. GLP-1 receptor Ist line: lixisenatide
agonists
-10mcg sc OD for 14 days,
increased to 20mcg OD
2nd line: Bydureon (exenatide)
modified release, if patient does
not tolerate lixisenatide
-2mg sc once weekly
Patients with a suboptimal
response (not quite reaching
NICE criteria) to lixisenatide but
not suitable for Bydureon:
liraglutide
-0.6-1.2mg sc OD (1.8mg OD is
not recommended by NICE)
Non-formulary: Byetta (exenatide)
-Caution if prescribing gliptins in patients with a
history of heart failure. An increased risk of
hospitalisation for heart failure was noted in
recent clinical trials (though no increase in
mortality was seen). If overt signs of heart failure
develop then gliptin medication should be
withdrawn.
-Gliptins should be considered prior to the use of
dapaglifozin
-To be used in line with NICE TA228:
-For use as dual therapy in combination with
metformin
-For use in combination with insulin with or
without other antidiabetic drugs
-NICE does not recommended use as triple
therapy with metformin and a sulfonylurea
-NICE does not recommended use with
pioglitazone
-Continue only if there is a reduction of ≥0.5%
points in HbA1c in 6 months (between 5 and 6
mmol/mol)
-Dose of concomitant insulin or sulfonylurea may
need to be reduced
-Check renal function before treatment and at
least annually
-Not recommended in moderate to severe renal
failure (eGFR<60ml/minute)
-Common side effects: dyslipidaemia, back pain,
genital infections, UTI, dysuria, polyuria
-Lixisenatide can be used in combination with
oral antidiabetic drugs (metformin,
sulphonylurea or pioglitazone) and/or basal
insulin
-Lixisenatide should not be given in combination
with basal insulin and a sulphonylurea due to
increased risk of hypoglycaemia
-Dose of concomitant sulfonylurea or insulin may
need to be reduced with gliptin
-Lixisenatide is not recommended in severe
renal impairment (eGFR <30 ml/minute)
-Bydureon is not recommended in moderate to
severe renal impairment (eGFR <50 ml/minute)
-Liraglutide is not recommended if eGFR <60
ml/minute)
-Patients with no or very little response to one
GLP-1 receptor agonist should not be offered
another one. However, if a partial response to
lixisenatide (HbaA1c reduction >5 but
<11mmol/mol and weight loss of >1.5% but less
than 3% body weight) is seen, then consider
switching to Bydureon or liraglutide if there are
strong reasons to persist with GLP-1 receptor
Date approved: November 2013
Approved by: Medicines Management Committee
Review date: November 2014, or earlier as appropriate
3
agonist therapy.
-Severe pancreatitis (sometimes fatal) has been
reported rarely with exenatide. Patients or their
carers should be told how to recognise signs
and symptoms of pancreatitis and advised to
seek prompt medical attention if symptoms such
as abdominal pain, nausea, and vomiting
develop; discontinue permanently if pancreatitis
is diagnosed. Pancreatitis is much commoner in
patients with diabetes and it is not clear if the
reported cases of pancreatitis merely reflect this
or if the true rate of pancreatitis is increased. An
increased rate of pancreatitis has not been seen
in clinical trials.
Lixisenatide, Bydureon (exenatide) modified release and liraglutide recommendations (NICE):
Triple therapy
-Can be used in triple therapy regimens (in combination with metformin and a sulphonylurea, or metformin
and pioglitazone), and the person should have an HbA1c of 59 mmol/mol (7.5%) or above, with:
 a BMI ≥ 35 kg/m2 in those of European family origin (with appropriate adjustment for other ethnic
groups) and specific psychological or medical problems associated with high body weight, or
 BMI < 35 kg/m2, and therapy with insulin would have significant occupational implications or weight
loss would benefit other significant obesity-related comorbidities
-Only continue treatment if a reduction of at least 1% in HbA1c (11 mmol/mol) and a weight loss of at least
3% of initial body weight is achieved at 6 months
Lixisenatide, Bydureon (exenatide) modified release and liraglutide recommendations (NICE): Dual
therapy
-Can be used in dual therapy regimens (in combination with metformin or a sulphonylurea), only if
 the person is intolerant of either metformin or a sulphonylurea, or metformin or a sulphonylurea is
contraindicated, and
 the person is intolerant of thiazolidinediones and DPP-4 inhibitors, or thiazolidinediones and DPP4 inhibitors is contraindicated
-Only continue treatment if a reduction of at least 1% in HbA1c (11 mmol/mol) is achieved at 6 months
Date approved: November 2013
Approved by: Medicines Management Committee
Review date: November 2014, or earlier as appropriate
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