Merck : Metformin Products, including Glucophage® Approved for Type 2 Diabetes Patients with Moderate Renal Impairment in Europe

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December 21, 2016

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Metformin Products, including Glucophage®Approved for Type 2 Diabetes Patients with Moderate Renal Impairment in Europe

• European Commission decision confirms Metformin for treatment in type 2 diabetes patients with moderate renal impairment, which will lead to extended treatment access
• Extended treatment for type 2 diabetes patients, who develop advanced kidney problems, reflected in label change of metformin- containing products including Glucophage®and Glucovance®
• Merck supported the referral with nearly 60 years of post-marketing safety and efficacy experience

Darmstadt, Germany, December 21, 2016 - Merck, a leading science and technology company, today announced that the European Commission (EC) has authorized the extension of the label for all metformin-containing products, including the Glucophage®product portfolio and Glucovance®, for the treatment of type 2 diabetes patients. The label change lifts the contraindication for stable moderate renal failure CKD (chronic kidney disease) stage 3, but adds some dose limitations. This change allows a large additional group of type 2 diabetes patients with reduced kidney function to benefit from the treatment: In a recent analysis in CPRD, a UK medical record database, 32.7% of all diabetic patients had CKD stage 3, with 23.2% in CKD stage 3a and 9.5% in CKD stage 3b1.

"We are pleased to see that the decision of the European Commission now confirms metformin can be safely used in type 2 diabetic patients with moderate renal

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failure," said Luciano Rossetti MD, Executive Vice President, Global Head of Research

& Development at the biopharma business of Merck. "Since we brought Glucophage®to the market we, and others, have continued to research on metformin, which is now amongst the best investigated oral medications for type 2 diabetes. The lift of the contraindication is, at least in part, also a result of our research, and it further supports the safe and effective use of metformin as first line treatment in patients with type 2 diabetes."

Following a routine evaluation of the safety of metformin medicines, it was found that patients with moderate renal failure may stand to benefit from treatment with metformin based on scientific evidence and clinical guidelines, and that the contraindication may therefore no longer be justified. The European Medicines Agency (EMA) issued an Article 31 referral requesting a cumulative review of the benefit and risk in this patient group across all metformin-selling companies in the European Union. Leveraging around 60 years of experience in market as the metformin originator, Merck supported the EMA request by providing a comprehensive analysis of all available clinical and post-marketing data on the efficacy and safety of metformin in patients with CKD stage 3. The data submitted by all companies was reviewed by EMA and as a result, the CHMP issued a positive opinion on lifting the contraindication for treatment of type 2 diabetes patients with renal impairment CKD stage 3 in October.

Following the EC decision the Summary of Product Characteristics (SmPC) will be updated to include details about the use of Metformin in type 2 diabetic patients with moderate renal failure in all Merck products containing metformin such as Glucophage®, Glucophage®XR, Stagid®and Glucovance®. Glucophage®is already today on label in patients with CKD stage 3a in Europe and CKD stage 3a and b in Switzerland.

References

1) McDonald HI, Thomas SL, Millett ERC, Nitsch D. CKD and the risk of acute, community-acquired infections among older people with diabetes mellitus: A retrospective cohort study using electronic health records. American Journal of Kidney Diseases 2015:66:60-8

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.

The Glucophage®product portfolio comprises: Glucophage®IR (immediate release) and Glucophage®XR (extended release). In addition, Merck produces Glucovance®a fixed dose combination of metformin and glibenclamide.

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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 2015, Merck generated sales of € 12.85 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.