Xigduo
Active Substance: metformin hydrochloride /
dapagliflozin propanediol monohydrate
Common Name: dapagliflozin / metformin
ATC Code: A10BD15
Marketing Authorisation Holder: Bristol-Myers Squibb/AstraZeneca EEIG
Active Substance: metformin hydrochloride / dapagliflozin propanediol
monohydrate
Status: Authorised
Authorisation Date: 2014-01-16
Therapeutic Area: Diabetes Mellitus, Type 2
Pharmacotherapeutic Group: Film-coated tablet
Therapeutic Indication
Xigduo is indicated in adults aged 18 years and
older with type 2 diabetes mellitus as an adjunct to diet and exercise to
improve glycaemic control:
in patients inadequately controlled
on their maximally tolerated dose of metformin alonein combination with other glucose
lowering medicinal products, including insulin, in patients inadequately
controlled with metformin and these medicinal products>/li>in patients already being treated
with the combination of dapagliflozin and metformin as separate tablets.
What is Xigduo and what is it used
for?
Xigduo is a diabetes medicine that contains the
active substances dapagliflozin and metformin. It is used, together with diet
and exercise, to control the blood glucose (sugar) levels in adults with type 2
diabetes whose disease is not satisfactorily controlled with metformin alone,
or in combination with other diabetes medicines, including insulin, when these
medicines together with metformin are not providing adequate control of the
diabetes. Xigduo can also be used to replace dapagliflozin and metformin taken
as separate tablets.
How is Xigduo used?
Xigduo is available as tablets (5 mg
dapagliflozin/850 mg metformin and 5 mg dapagliflozin/1,000 mg metformin) and
can only be obtained with a prescription.
The recommended dose is one tablet taken twice a
day with a meal; the strength should be chosen so that in total, patients
receive 10 mg of dapagliflozin each day and the same dose (or as close as
possible to it) of metformin they were already taking before starting Xigduo.
When Xigduo is used with insulin, the doctor may need to lower the dose of
insulin to reduce the risk of hypoglycaemia (low blood sugar levels).
How does Xigduo work?
Type 2 diabetes is a disease in which the pancreas
does not make enough insulin to control the levels of glucose in the blood or
when the body is unable to use insulin effectively. This leads to high levels
of glucose in the blood.
Xigduo contains two different active substances,
which work in different ways:
dapagliflozin works by blocking a
protein in the kidneys called sodium-glucose co-transporter 2 (SGLT2).
SGLT2 absorbs glucose from the urine into the bloodstream as the blood is
filtered in the kidneys. By blocking the action of SGLT2, dapagliflozin
causes more glucose to be removed via the urine, thereby reducing the
levels of glucose in the blood. Dapagliflozin has been authorised in the
European Union (EU) as Forxiga since 2012;metformin works mainly by
inhibiting glucose production and reducing its absorption in the gut. It
has been available in the EU since the 1950s.
As a result of the action of both active
substances, the blood glucose is reduced and this helps to control type 2
diabetes.
What benefits of Xigduo have been
shown in studies?
Dapagliflozin in combination with metformin was
evaluated in 6 main studies involving 3,200 adults with type 2 diabetes. The
majority of these data had already been used in the authorisation of Forxiga.
In one main study, when dapagliflozin was used at a
dose of 5 mg twice a day in addition to metformin (the same combination as in
Xigduo), it decreased HbA1c levels by 0.65% after 16 weeks, compared with a
reduction of 0.30% with placebo (a dummy treatment) and metformin. HbA1c
(glycosylated haemoglobin) is a substance in the blood which gives an
indication of how well the blood glucose is controlled. Two other studies
showed that dapagliflozin taken with metformin and another diabetes medicine,
sitagliptin or insulin, for 24 weeks, further decreased HbA1c: the
dapagliflozin combination decreased HbA1c levels by 0.40% more than placebo and
metformin when added to sitagliptin, and by 0.61% more than placebo and
metformin when added to insulin. Further studies confirmed that different doses
of dapagliflozin with metformin decreased HbA1c more than placebo plus
comparable doses of metformin, and that dapagliflozin plus metformin was at
least as effective in reducing HbA1c levels as the diabetes medicine glipizide
(a type of medicine known as a sulphonylurea). A sixth study showed that after
24 weeks of treatment, patients taking dapagliflozin plus metformin had an
average reduction in body weight of around 2 kg more than those taking placebo
plus metformin.
What are the risks associated with
Xigduo?
The most common side effects with Xigduo (which may
affect more than 1 in 10 people) are hypoglycaemia (when used together with
insulin or a sulphonylurea) and gastrointestinal symptoms (symptoms affecting
the stomach and gut). For the full list of all side effects reported with
Xigduo, see the package leaflet.
Xigduo must not be used in:
patients with diabetic ketoacidosis
(high blood levels of acids called ‘ketones’) or diabetic pre-coma (a
dangerous condition that can occur in diabetes);patients with reduced liver
function;patients with moderate or severe
reductions in kidney function or with acute conditions that could
potentially alter kidney function such as dehydration, severe infection or
shock;patients with diseases that could
cause tissue hypoxia (reduced levels of oxygen in body tissues);patients with alcoholism.
For the full list of restrictions, see the package
leaflet.
Why is Xigduo approved?
The Agency’s Committee for Medicinal Products for
Human Use (CHMP) decided that Xigduo’s benefits are greater than its risks and
recommended that it be approved for use in the EU. The CHMP considered Xigduo
to be effective at controlling blood glucose levels; it also leads to weight
loss, which is considered beneficial in patients with diabetes. The CHMP also
noted that giving the combination of dapagliflozin and metformin as a single
tablet could provide an additional treatment option for patients with type 2
diabetes, and may improve adherence to treatment. Regarding its safety profile,
this was considered similar to the safety profile of dapagliflozin.
What measures are being taken to
ensure the safe and effective use of Xigduo?
A risk management plan has been developed to ensure
that Xigduo is used as safely as possible. Based on this plan, safety
information has been included in the summary of product characteristics and the
package leaflet for Xigduo, including the appropriate precautions to be
followed by healthcare professionals and patients.
Other information about Xigduo
The European Commission granted a marketing
authorisation valid throughout the European Union for Xigduo on 16 January
2014.
For more information about treatment with Xigduo,
read the package leaflet (also part of the EPAR) or contact your doctor or
pharmacist.
Source: European Medicines Agency
