Medical DevicesCHMP Recommends 'Januvia(R)'(sitagliptin), From MSD, For Restricted First Line Use In European Union
Merck & Co., Inc. (Whitehouse Station, N.J., U.S.A.), which operates in many countries as Merck Sharp & Dohme (MSD), has received a positive opinion from the European Medicines Agency"s (EMEA) Committee for Medicinal Products for Human Use (CHMP) recommending restricted first line use of "Januvia" (sitagliptin) for the treatment of type 2 diabetes. With this positive opinion, the CHMP recommends that sitagliptin be indicated to improve glycaemic control when diet and exercise alone do not provide adequate glycaemic control and when metformin is inappropriate due to contraindications or intolerance. If this opinion is accepted by the European Commission, sitagliptin will be the only diabetes treatment in the DPP-4 inhibitor class to have a restricted first line indication.
The announcement follows the recent European Commission approval of both sitagliptin and the fixed dose combination of sitagliptin and metformin for use in combination with a PPARÎÆ agonist (i.e., a thiazolidinedione) and metformin, when diet and exercise plus dual therapy with these agents do not provide adequate glycaemic control. The fixed dose combination of sitagliptin and metformin is not currently available in some countries, such as the UK.
"Merck is committed to helping physicians and people with diabetes try to achieve target glycaemic levels and successfully manage their disease," said Stefan Oschmann, president, Europe, Middle East, Africa and Canada, MSD. "We welcome the announcements from both the CHMP and European Commission, which further reinforce that sitagliptin and the fixed dose combination of sitagliptin and metformin can be used in combination therapy with a variety of diabetes treatments in appropriate patients."
Sitagliptin is a highly selective, once-daily DPP-4 inhibitor that enhances a natural body system called the incretin system to help regulate blood sugar by increasing levels of active GLP-1 and GIP hormones; it inhibits DPP-4 over 24 hours. The fixed dose combination of sitagliptin and metformin targets all three key defects of diabetes: insulin deficiency from pancreatic beta cells, insulin resistance, and overproduction of glucose by the liver. Sitagliptin is the first approved medicine in the DPP-4 inhibitor class of oral treatments. It has been approved in over 80 countries, and to date there have been more than 11 million prescriptions dispensed worldwide.
About sitagliptin
Sitagliptin is a member of a class of oral anti-hyperglycaemic agents called dipeptidyl peptidase 4 (DPP-4) inhibitors and is licensed as an adjunct to diet and exercise for the treatment of type 2 diabetes in combination with either metformin and/or a sulphonylurea, or in combination with metformin and/or a PPARy agonist, when the other agent(s) do not provide adequate glycaemic control. The drug enhances the body"s own ability to lower blood sugar levels by increasing the levels of the body"s own active incretins, called GLP-1 and GIP.
The recommended dose of sitagliptin is 100mg once daily, with or without food, for all approved indications.
Clinical experience with sitagliptin in patients with moderate to severe renal insufficiency is limited. Therefore sitagliptin is not recommended in this patient population. No dosage adjustment is needed for patients with mild to moderate hepatic insufficiency, and sitagliptin has not been studied in patients with severe hepatic insufficiency. Sitagliptin is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients. This medicine should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, or in woman who are lactating or pregnant.
In clinical studies, the adverse reactions reported, regardless of investigator assessment of causality, in >3% of patients treated with sitagliptin as monotherapy and in combination therapy with metformin or pioglitazone and more commonly than in patients treated with placebo, were upper respiratory tract infection, nasopharyngitis, and diarrhea.
About the fixed dose combination of sitagliptin and metformin
The fixed dose combination of sitagliptin and metformin is indicated as an adjunct to diet and exercise to improve glycaemic control in patients with type 2 diabetes inadequately controlled on metformin alone or those already being treated with the combination of sitagliptin and metformin. The fixed dose combination is also indicated for use in combination with a sulfonylurea (SU) or with a PPARy agonist as an adjunct to diet and exercise in patients inadequately controlled on metformin and an SU or metformin and a PPARy agonist. The dose of antihyperglycaemic therapy with fixed dose combination of sitagliptin and metformin should be individualised on the basis of the patient"s current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100mg sitagliptin.
Initial therapy with sitagliptin or the fixed dose combination of sitagliptin and metformin is not currently licensed, and the fixed dose combination of sitagliptin and metformin is not currently available in some countries, such as the UK.
The fixed dose combination of sitagliptin and metformin is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients; diabetic ketoacidosis or diabetic pre-coma; moderate and severe renal impairment or abnormal creatinine clearance, acute conditions with the potential to alter renal function; acute or chronic disease which may cause tissue hypoxia; hepatic impairment; acute alcohol intoxication; alcoholism and lactation. This drug combination should not be used in patients with type 1 diabetes.
Patients taking the fixed dose combination of sitagliptin and metformin with a sulfonylurea, a medication known to cause hypoglycaemia, may be at a higher risk of hypoglycaemia than those patients taking the fixed dose combination of sitagliptin and metformin alone. Therefore, a reduction in the dose of the sulfonylurea may be required.
In clinical studies, the most common adverse reactions reported, regardless of investigator assessment of causality, in ð‰¥5% of patients and more commonly than in patients treated with placebo were as follows: diarrhea, upper respiratory tract infection, and headache (for initial sitagliptin and metformin combination therapy); nasopharyngitis (for sitagliptin monotherapy); and diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache (for metformin therapy).
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