Velmetia
Active Substance: sitagliptin / metformin
hydrochloride
Common Name: sitagliptin / metformin
ATC Code: A10BD07
Marketing Authorisation Holder: Merck Sharp & Dohme Ltd
Active Substance: sitagliptin / metformin hydrochloride
Status: Authorised
Authorisation Date: 2008-07-16
Therapeutic Area: Diabetes Mellitus, Type 2
Pharmacotherapeutic Group: Drugs used in diabetes
Therapeutic Indication
For patients with type-2 diabetes mellitus:
Velmetia is indicated as an adjunct
to diet and exercise to improve glycaemic control in patients inadequately
controlled on their maximal tolerated dose of metformin alone or those
already being treated with the combination of sitagliptin and metformin.Velmetia is indicated in
combination with a sulphonylurea (i.e. triple combination therapy) as an
adjunct to diet and exercise in patients inadequately controlled on their
maximal tolerated dose of metformin and a sulphonylurea.Velmetia is indicated as triple
combination therapy with a PPAR agonist (i.e. a thiazolidinedione) as an
adjunct to diet and exercise in patients inadequately controlled on their
maximal tolerated dose of metformin and a PPAR agonist.Velmetia is also indicated as add
on to insulin (i.e. triple combination therapy) as an adjunct to diet and
exercise to improve glycaemic control in patients when stable dosage of
insulin and metformin alone do not provide adequate glycaemic control.
What is Velmetia?
Velmetia is a medicine that contains two active
substances, sitagliptin and metformin hydrochloride. It is available as tablets
(50 mg sitagliptin / 850 mg metformin hydrochloride; and 50 mg sitagliptin /
1,000 mg metformin hydrochloride).
What is Velmetia used for?
Velmetia is used in patients with type-2 diabetes
to improve the control of blood glucose (sugar) levels. It is used in addition
to diet and exercise in the following ways:
in patients who are not
satisfactorily controlled on metformin (an antidiabetes medicine) used on
its own;in patients who are already taking
a combination of sitagliptin and metformin as separate tablets;in combination with a
sulphonylurea, a PPAR-gamma agonist such as a thiazolidinedione, or
insulin (other types of antidiabetes medicine) in patients who are not
satisfactorily controlled on this medicine and metformin.
The medicine can only be obtained with a
prescription.
How is Velmetia used?
Velmetia is taken twice a day. The strength of
tablet to use depends on the dose of the other antidiabetes medicines that the
patient was taking before. If Velmetia is taken with a sulphonylurea or
insulin, the dose of the sulphonylurea or insulin may need to be lowered, to
avoid hypoglycaemia (low blood sugar levels).
The maximum dose of sitagliptin is 100 mg a day.
Velmetia should be taken with food to avoid any stomach problems caused by
metformin.
How does Velmetia work?
Type-2 diabetes is a disease in which the pancreas
does not make enough insulin to control the level of glucose in the blood or
when the body is unable to use insulin effectively. The active substances in
Velmetia, sitagliptin and metformin hydrochloride, each have a different mode
of action.
Sitagliptin is a dipeptidyl-peptidase-4 (DPP-4)
inhibitor. It works by blocking the breakdown of ‘incretin’ hormones in the
body. These hormones are released after a meal and stimulate the pancreas to
produce insulin. By increasing the levels of incretin hormones in the blood,
sitagliptin stimulates the pancreas to produce more insulin when blood glucose
levels are high. Sitagliptin does not work when the blood glucose is low.
Sitagliptin also reduces the amount of glucose made by the liver, by increasing
insulin levels and decreasing the levels of the hormone glucagon. Sitagliptin
has been authorised in the European Union (EU) as Januvia and Xelevia since
2007, and as Tesavel since 2008.
Metformin works mainly by inhibiting glucose
production and reducing its absorption in the gut. Metformin has been available
in the EU since the 1950s.
As a result of the action of both active substances,
blood glucose levels are reduced and this helps to control type-2 diabetes.
How has Velmetia been studied?
Sitagliptin on its own as Januvia / Xelevia /
Tesavel can be used with metformin, and with both metformin and a
sulphonylurea, in type-2-diabetes patients. The company presented the results
of three studies of Januvia / Xelevia to support the use of Velmetia in
patients who were not satisfactorily controlled on their existing metformin
treatment.
Two of the studies looked at sitagliptin as an
add-on to metformin: the first compared it with placebo (a dummy treatment) in
701 patients, and the second compared it with glipizide (a sulphonylurea) in
1,172 patients. The third study compared sitagliptin with placebo, when used as
an add-on to glimepiride (another sulphonylurea), with or without metformin, in
441 patients. The results of three further studies were used to support the use
of Velmetia. The first included 1,091 patients who were not satisfactorily
controlled on diet and exercise alone and compared the effect of Velmetia with
that of metformin or sitagliptin alone. The second included 278 patients who
were not satisfactorily controlled on the combination of metformin and
rosiglitazone (a PPAR-gamma agonist) and compared the effects of adding
sitagliptin or placebo. The third included 641 patients who were not
satisfactorily controlled on a stable dose of insulin, three-quarters of whom
were also taking metformin. This study also compared the effects of adding
sitagliptin or placebo.
In all of the studies, the main measure of
effectiveness was the change in the levels of a substance in the blood called
glycosylated haemoglobin (HbA1c), which gives an indication of how well the
blood glucose is controlled.
The company carried out additional studies to show
that the active substances in Velmetia are absorbed by the body in the same way
as the two medicines given separately.
What benefit has Velmetia shown
during the studies?
Velmetia was more effective than metformin alone.
Adding 100 mg sitagliptin to metformin reduced HbA1c levels by 0.67% (from
around 8.0%) after 24 weeks, compared with a fall of 0.02% in the patients
adding placebo. The effectiveness of adding sitagliptin to metformin was similar
to that of adding glipizide. In the study in which sitagliptin was added to
glimepiride and metformin, the levels of HbA1c were reduced by 0.59% after 24
weeks, compared with an increase of 0.30% in the patients adding placebo.
In the first of the three further studies, Velmetia
was more effective than metformin or sitagliptin alone. In the second, HbA1c
levels were reduced by 1.03% after 18 weeks in patients adding sitagliptin to
metformin and rosiglitazone, compared with a fall of 0.31% in those adding placebo.
Finally, they were reduced by 0.59% after 24 weeks
in patients adding sitagliptin to insulin, compared with a fall of 0.03% in
those adding placebo. There was no difference in this effect between the
patients also taking metformin and those not taking it.
What is the risk associated with
Velmetia?
The most common side effect with Velmetia (seen in
between 1 and 10 patients in 100) is nausea (feeling sick). For the full list
of all side effects reported with Velmetia, see the package leaflet.
Velmetia must not be used in people who are
hypersensitive (allergic) to sitagliptin, metformin or any of the other
ingredients. It must not be used in patients who have diabetic ketoacidosis or
pre‑coma (dangerous conditions that can occur in diabetes), problems with the
kidneys or liver, conditions that may affect the kidneys, or a disease that
causes a reduced supply of oxygen to the tissues such as failure of the heart
or lungs or a recent heart attack. It must also not be used in patients who
consume excessive amounts of alcohol or who are alcoholic, or in women who are
breast-feeding. For the full list of restrictions, see the package leaflet.
Why has Velmetia been approved?
The CHMP decided that Velmetia’s benefits are
greater than its risks and recommended that it be given marketing
authorisation.
Other information about Velmetia
The European Commission granted a marketing
authorisation valid throughout the EU for Velmetia on 16 July 2008.
For more information about treatment with Velmetia,
read the package leaflet (also part of the EPAR) or contact your doctor or
pharmacist.
Source: European Medicines Agency
