Merck's Glucophage® SR Receives Label Extension for Patients at High Risk of Type 2 Diabetes in the

Not intended for U.S. based media 

• Glucophage^® SR offers UK healthcare professionals the first licensed treatment option for overweight adult patients at high risk of progression to type 2 diabetes, after failure of intensive lifestyle changes 
• Non-diabetic hyperglycemia, also known as impaired glucose regulation or pre-diabetes^[1], was estimated in 2009 to affect around seven million adults in the UK^[2] and is predicted to significantly increase in the coming years^[3] 

Merck, a leading science and technology company, today announced that the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK has authorized Glucophage^® SR (sustained release formulation; metformin), for the reduction in the risk or delay of the onset of type 2 diabetes in adult, overweight patients with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), and/or increased glycated hemoglobin (HbA1c), when intensive lifestyle changes for 3 to 6 months have failed. This condition is referred to by a variety of names in medical guidelines, i.e. as non-diabetic hyperglycemia, as impaired glucose regulation, or as pre-diabetes.^[1],[4]-[7] Merck has already received authorization for this indication in several countries around the world. Through earlier intervention, patients can reduce their risk of developing type 2 diabetes^[8] as well as complications that can lead to serious health issues.^[5]

"We are pleased that patients at risk of diabetes in the UK now have a medicinal treatment option to help them delay the onset of diabetes, when intensive lifestyle changes alone are not enough to work against the progression to type 2 diabetes," said Luciano Rossetti MD, Executive Vice President, Global Head of Research & Development at the biopharma business of Merck: "According to WHO, diabetes is considered a global pandemic and we are committed to helping slow the rapidly growing incidence. This is an important achievement as it can help play a role in reducing the burden of type 2 diabetes for patients."

The authorization is based on clinical data on the efficacy of Glucophage^® for the treatment of non-diabetic hyperglycemia, primarily gathered in the large US Diabetes Prevention Program (DPP)^[8] and subsequent Diabetes Prevention Program Outcome Study (DPPOS)^[9]-[11] with Glucophage^®. This data was complemented by comprehensive safety and efficacy data on Glucophage^® collected since its first use in patients in 1957.

Non-diabetic hyperglycemia is triggered by insulin resistance, that causes cells to be unable to effectively utilize insulin, which is needed to get the glucose inside the cells and to stabilize blood glucose levels. This is also called impaired glucose tolerance (IGT). As a response, more insulin may be produced, which may again lose efficacy over time. Eventually, blood glucose levels in the body rise to higher than normal values even between meals, which is called impaired fasting glucose (IFG). Elevated blood glucose levels are also often measured as an average over time through HbA1c. The corresponding lab values for diagnosis of non-diabetic hyperglycemia as per UK's National Institute for Health and Care Excellence (NICE) guidelines, are fasting glucose between 100 and 125 mg/dl, and/or 140 to 199mg/dl in a glucose tolerance test, and/or HbA1c between 6.0 and 6.4%.^[1]

From this stage of non-diabetic hyperglycemia, the disease may then further slowly progress to overt type 2 diabetes. Intensive lifestyle changes will be used as a first counter action. If the patient is still at high risk of progression to type 2 diabetes after 3 to 6 months with worsening glycemic control despite intensive lifestyle measures, Glucophage^® SR is now an additional treatment option that may help to slow the deterioration of the blood glucose levels. Treatment with Glucophage^® SR must be based on a risk score incorporating appropriate measures of glycemic control and including evidence of high cardiovascular risk. A benefit in the reduction of risk or delay of the onset of type 2 diabetes has not yet been established in patients 75 years and older.

About Glucophage^® 

Glucophage^® (metformin hydrochloride) is a prescription-only medicine indicated for the treatment of type 2 diabetes mellitus, particularly in overweight patients when diet and exercise alone have failed. In adults, Glucophage^® may be given alone or with oral antidiabetic agents, or with insulin. The most commonly reported side effects with Glucophage^® SR are gastro-intestinal disturbances that may occur during treatment initiation and resolve spontaneously in most cases.

The Glucophage^® product portfolio comprises: Glucophage^® IR (immediate release formulation) and Glucophage^® SR (sustained release formulation). Outside of the UK, Glucophage^® SR is known as Glucophage^® XR (extended release). In addition, Merck produces Glucovance^® a fixed dose combination of metformin and glibenclamide.

About Merck 

Merck is a leading science and technology company in healthcare, life science and performance materials. Around 50,000 employees work to further develop technologies that improve and enhance life - from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2016, Merck generated sales of € 15.0 billion in 66 countries.

Founded in 1668, Merck is the world's oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.

References 

NICE guideline ph38: Type 2 diabetes: prevention in people at high risk. Published 12 July 2012. Available at: https://www.nice.org.uk/guidance/ph38/chapter/8-glossary#pre-diabetes

Diabetes UK. (2009). Preventing the Type 2 diabetes epidemic: October 2009. Available at: https://www.diabetes.org.uk/Documents/Reports/PrediabetesPreventingtheType2diabetesepidemicOct2009report.pdf

IDF (International Diabetes Federation). IDF Diabetes Atlas, seventh edition 2015.

ADA (American Diabetes Association). Standards of Medical Care in Diabetes. Diabetes Care 2013; 36(1):S11-66

ESC (European Society of Cardiology). Diabetes, Prediabetes and Cardiovascular Diseases. Available at: http://www.escardio.org/guidelines-surveys/esc-guidelines/Pages/ diabetes.aspx

Ryden L, Grant PJ, Anker SD et al. ESC Guidelines on diabetes, prediabetes, and cardiovascular diseases developed in collaboration with the EASD - Summary. Eur Heart J 2013; 34:3035-3087

IDF (International Diabetes Federation). (2012). Clinical Guidelines Task Force: Global guideline for the management of type 2 diabetes.

DPP Research Group. Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. N Engl J Med 2002; 346:393-403

DPP Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 2009; 374:1677-1686

Perreault L, Pan Q, Mather KJ et al. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet 2012; 379(9833):2243-2251

DPP Research Group. Long-term Effects of Lifestyle Intervention or Metformin on Diabetes Development and Microvascular Complications: the DPP Outcomes Study. The Lancet Diabetes and Endocrinology 2015 3(11):866-875