New NICE Guideline for Type 2 Diabetes Recognises Benefits From Newer Agents for Blood Glucose Control

LONDON - For Healthcare and Pharmaceutical Correspondents Only

- NICE Recommends Considering DPP-4 Inhibitors as a Second Line Treatment Option in Appropriate Patients

Merck Sharp & Dohme Limited (MSD) welcomes the publication of the guideline for type 2 diabetes newer agents1 from the National Institute for Health and Clinical Excellence (NICE) in the UK, which recommends considering a range of newer therapy options, including ‘Januvia’ (sitagliptin). The guideline recommends that the DPP-4 inhibitor class, which includes sitagliptin, should be considered as a second line therapy instead of a sulphonylurea (SU) when blood glucose control remains or becomes inadequate (HbA1c greater than or equal to 6.5% or other higher level agreed with the individual) with metformin in patients at significant risk of hypoglycaemia or its consequences, or if a patient does not tolerate an SU or an SU is contraindicated.(1)

Professor Anthony Barnett, a leading diabetologist from the UK said, “One of the key issues when considering treatment options is striking a balance between achieving optimal glycaemic control while also minimising the risk of hypoglycaemia, and the newer treatments provide us with a wider choice of options. NICE should be applauded for recognising these newer agents, as this represents a significant milestone in the treatment of type 2 diabetes and may have an impact across the rest of Europe. We now have an array of effective treatment options to offer appropriate patients whose blood glucose is not adequately controlled by first-line treatments plus diet and exercise, to help get their blood sugar under control in order to carry on with their everyday lives.”

It is estimated that there are over 53.2 million people in Europe living with diabetes and that this figure is set to rise to 64.1 million by 2025.(2) A recent MSD Diabetes survey of healthcare professionals (HCPs) across Europe found that the majority (78%) felt that fewer prescribing restrictions would aid more effective disease management.(3)

Some of the newer agents, such as the DPP-4 class, have a lower risk of hypoglycaemia and weight gain. As highlighted within the NICE guideline, the latest data on the DPP-4 inhibitor sitagliptin has shown that treatment with sitagliptin was associated with fewer hypoglycaemic events compared to treatment with metformin and glipizide, a sulphonylurea, 5% versus 32% respectively.(4) When added to a sulfonylurea, sitagliptin has been associated with an increased risk of hypoglycaemia. Therefore, a reduction in the dose of the sulphonylurea may be necessary.

Dr Martin Hadley-Brown, chairman of the Primary Care Diabetes Society in the UK, said, “The guideline for type 2 diabetes newer agents is important for healthcare professionals because it helps clarify which patients are appropriate candidates for these newer treatments. With a chronic condition such as diabetes it is essential that patients are educated about their condition, have access to a wide range of treatment options and maintain the best quality of life possible. The guideline for type 2 diabetes newer agents certainly supports these efforts.”

In addition, the NICE guideline recognises the role of sitagliptin as the only DPP-4 inhibitor licensed for use in triple therapy with metformin and an SU where metformin and an SU do not adequately control blood sugar (HbA1c greater than or equal to 7.5% or other higher level agreed with the individual) and insulin is considered inappropriate or unacceptable to the patient.(1)

As a once-daily tablet, sitagliptin provides a convenient treatment option for patients and has over ten million prescriptions worldwide since launch.(5) “We are delighted that, in its guideline for type 2 diabetes newer agents, NICE has recognised the DPP-4 inhibitor class as a potential alternative to SU in selected patients” Dr Paul Leigh, MSD Diabetes, commented. “At MSD, we strive to develop new medicines that can make a difference to patients’ lives, so it is pleasing to know that patients and HCPs can now benefit from a wider range of treatments.”

Notes to Editors

About sitagliptin

Sitagliptin is a member of a class of oral anti-hyperglycaemic agents called dipeptidyl peptidase 4 (DPP-4) inhibitors and is licensed in the UK for the treatment of type 2 diabetes in combination with either metformin and/or a sulphonylurea, or in certain patients, with a PPARy agonist (i.e. thiazolidinedione), when diet and exercise plus the other agent(s) do not provide adequate glycaemic control.(6)

Sitagliptin 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.(6)

Sitagliptin should not be used in patients with moderate or severe renal impairment or in patients with hepatic insufficiency. It is contraindicated in patients with: hypersensitivity to the active substances or to any of the excipients; diabetic ketoacidosis, diabetic pre-coma; acute conditions with the potential to alter renal function; acute or chronic disease which may cause tissue hypoxia; acute alcohol intoxication, alcoholism; or in woman who are lactating or pregnant. No liver function tests need to be performed prior to the initiation of treatment. See Summary of Product Characteristics for further details.

About hypoglycaemia

Hypoglycaemia occurs when the level of glucose in the blood falls too low, usually under 4 mmol/l. People with diabetes who take insulin and/or certain diabetes tablets are at risk of having hypoglycaemia. It may occur if someone has taken too much diabetes medication, delayed or missed a meal or snack, not eaten enough carbohydrate, taken part in unplanned or more strenuous exercise than usual, and has been drinking alcohol without food. Sometimes there is no obvious cause. When hypoglycaemia happens the person often experiences ‘warning signs’, which occur as the body tries to raise the blood glucose level. These ‘warning signs’ vary from person to person but often include feeling shaky, sweating, tingling in the lips, going pale, heart pounding, confusion and irritability.

Treatment is usually very simple and requires taking some fast acting carbohydrate, such as a sugary drink or some glucose tablets, and following this up with some longer acting carbohydrate, such as a cereal bar. If left untreated the person might, eventually, become unconscious and would need to be treated with an injection of glucagon (a hormone that raises blood glucose levels). But in the vast majority of cases the body will release its own stores of glucose and raise the blood glucose level to normal, though this may take several hours.(7)

About NICE

The National Institute for Health and Clinical Excellence (NICE)is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health in the UK.

NICE produces guidance in three areas of health: - public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector - health technologies - guidance on the use of new and existing medicines, treatments and procedures within the NHS - clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS

NICE guidance is developed using the expertise of the NHS and the wider healthcare community including NHS staff, healthcare professionals, patients and carers, industry and the academic world.

Other agents reviewed in the NICE guideline on newer agents for blood glucose in type 2 diabetes include the Thiazolidinediones, GLP-1 mimetic and long-acting human insulin analogues.

About Merck Sharp & Dohme Limited

Merck Sharp & Dohme Limited (MSD) is the UK subsidiary of Merck & Co., Inc., of Whitehouse Station, New Jersey, USA, a leading research-based pharmaceutical company that discovers, develops, manufactures and markets a wide range of innovative pharmaceutical products to improve human health.

‘Januvia’(R) is a Registered Trademark of Merck & Co., Inc., Whitehouse Station, New Jersey, USA.

References: (1) National Institute for health and Clinical Excellence. Type 2 diabetes: newer agents for blood glucose in type 2 diabetes. Review of NICE technology appraisal guidance 66. May 2009. www.nice.org.uk (2) Diabetes Atlas. www.eatlas.idf.org/ (3) Diabetes Impact Survey Report, MSD Diabetes. (4) Krobot KJ, Stein PP, Alen S et al. Lower risk of hypoglycaemia with sitagliptin compared to glipizide when added to ongoing metformin therapy: An analysis based on A1C-adjusted event rates. Abstract presented at the 68th Scientific Sessions of the American Diabetes Association, June 2008, San Francisco. (5) IMS Health, NPA(TM) Weekly, TRxs: data on file (6) ‘Januvia’ (sitagliptin). Summary of Product Characteristics. MSD UK 2007 (7) Diabetes UK. Guide to diabetes. www.diabetes.org.uk/Guide-to-diabetes/complications/short_term_complications/hypoglycaemia

For further information, please contact: Diane Wass / Louise Barr Merck Sharp & Dohme Limited Office: +44(0)1992-457272 / 462126 diane_wass@merck.com louise_barr@merck.com Georgie Griffith / Katie Armson Cohn & Wolfe Office: +44(0)20-7331-5369 / 5330 georgie.griffith@cohnwolfe.com katie.armson@cohnwolfe.com

Source: Merck Sharp & Dohme Limited

For further information, please contact: Diane Wass / Louise Barr, Merck Sharp & Dohme Limited, Office: +44(0)1992-457272 / 462126, diane_wass at merck.com, louise_barr at merck.com; Georgie Griffith / Katie Armson, Cohn & Wolfe, Office: +44(0)20-7331-5369 / 5330, georgie.griffith at cohnwolfe.com, katie.armson at cohnwolfe.com