British regulatory authority approves Glucophage® Extended Release (XR) for type 2 diabetes patients with moderate renal impairment stage 3a or stable chronic heart failure The approval is based on retrospective safety analyses and new clinical data Darmstadt, Germany, November 3, 2015 - Merck a leading science and technology company, today announced that the British Medicines and Healthcare products Regulatory Agency (MHRA), has approved on November 2 an updated labeling for Glucophage® XR (extended release metformin) for the treatment of patients with type 2 diabetes. The label change removes moderate renal impairment stage 3a and stable chronic heart failure from the list of the contraindications of Glucophage® XR. Earlier in the year, the French regulatory authority Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM), had already approved an update of the labeling for Glucophage® IR (immediate release metformin) removing the same contraindications. The label changes apply to all countries in the European Union. Glucophage® IR is approved by a Mutual Recognition Procedure, where France acted as the Reference Member State.
In the case of Glucophage® XR the label changes were approved via a Worksharing Procedure in the European countries involved, where the UK was acting as the Reference Member State. The decisions are based on analyses of Merck's extensive efficacy and safety data collected over many years as well as new clinical studies available for Glucophage®, which was first registered in 1959.
Luciano Rossetti, Head of Global Research and Development at Merck´s biopharma business commented: "We are pleased with the update to the indications of Glucophage® XR and Glucophage® IR in the treatment of type 2 diabetes patients with moderate renal impairment stage 3a and in patients with stable chronic heart failure. Metformin is the first line treatment for patients with type 2 diabetes as recommended by international guidelines1,2. We are therefore pleased that more patients can now benefit from this treatment."
Until now Glucophage® IR and Glucophage® XR were contraindicated when glomerular filtration rate (GFR) was below 60ml/min. However, extensive postmarketing and clinical study evidence presented to the regulatory authorities supported that use of Glucophage® XR and Glucophage® IR has an acceptable safety profile in type 2 diabetic patients with moderate renal impairment stage 3a (when GFR is between 45ml/min and 59ml/min)3 at a reduced dose (max. 1000 mg/day), with no higher risk of adverse events.
A number of studies have demonstrated that the use of Glucophage® in the treatment of type 2 diabetes patients with stable chronic congestive heart failure has an acceptable safety profile4,5,6,7. Until now metformin was contraindicated in heart failure in general due to the potential risk of lactic acidosis, a risk factor in acute worsening heart failure8.
In 2013, 382 million people were suffering from diabetes9 globally, and by 2035 this figure is predicted to rise to 592 million10.
The full Glucophage® XR and Glucophage® IR labeling information is available in the revised Summary of Product Characteristics (SmPCs). News Release Page 3 of 4 References 1. Kasia J et al., Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care 2011; 34(6): 1431-1437 2. Asian Pacific Type 2 Diabetes Policy Group Guidelines 2005: 20-21 3. Salpeter et al., Risk of Fatal and Nonfatal Lactic Acidosis with Metformin Use in Type 2 Diabetes Review Cochrane Library 2009 4 DOC ID 090006d180bf4a9a 4. Ekström et al., Effectiveness And Safety In Metformin In 51,675 Patients With Type 2 Diabetes And Different Levels Of Renal Function: A Cohort Study From The Swedish National Diabetes Register BMJ Open 20121;2:e001076 DOC ID 0900babe80613d82 5. Holman et al., 10-Year Follow-Up Of Intensive Glucose Control In Type 2 Diabetes. N Engl J Med 2008;359(15):1577-89. 6. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352(9131):854-65. 7. Viollet et al., Cellular and Molecular Mechanisms Of Metformin: An Overview. Clin Sci (Lond) 2012;122(6):253-70 8. Lipska et al., Use of Metformin in the Setting of Mild-to-Moderate Renal Insufficiency Diabetes Care 2011 34 (6) 1431-1437 9. World Health Assembly Follow-up to the political declaration of the high-level meeting of the General Assembly on the prevention and control of noncommunicable diseases 2013 10. Danaei G et al., National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants Circulation 2013; 127: 1493-1502 11. International Diabetes Federation Diabetes Atlas 2014 News Release Page 4 of 4 About Diabetes Diabetes has reached epidemic proportion in many regions of the world. Global studies demonstrate that the number of people with diabetes has reached 382 million in 20139 with 4.9 million deaths in 201411. Among adults, it is the leading cause of new cases of blindness, kidney failure, and amputations of feet and legs. A person with diabetes has a shorter life expectancy and has about twice the risk of dying on any given day as a person of similar age without diabetes11. 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. In children from 10 years old and adolescents, Glucophage® may be given alone or with insulin. A reduction of diabetic complications has been shown in overweight type 2 diabetic adult patients treated with Glucophage® as first-line therapy after diet failure. The most commonly reported side effects with Glucophage® are gastro-intestinal disturbances that may occur during treatment initiation and resolve spontaneously in most cases. Glucophage® is contraindicated in patients with a GFR below 45ml/min. The Glucophage® range comprises: Glucophage® IR (immediate release) and Glucophage® XR (extended release). In addition, Merck produces Glucovance® a fixed dose combination of metformin and glibenclamide.