'Janumet'TM (Sitagliptin/Metformin) Approved In The European Union For Treatment Of Type 2 Diabetes

Main Category: Diabetes
Also Included In: Regulatory Affairs / Drug Approvals
Article Date: 23 Jul 2008 - 1:00 PST

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Merck & Co., Inc.'s new combination product for type 2 diabetes, has been granted a marketing authorisation from the European Commission (EC). 'Janumet' (sitagliptin/metformin) helps patients lower blood sugar levels to help reach their treatment goal through the efficacy of sitagliptin, a DPP-4 inhibitor, and metformin, a mainstay of diabetes therapy. Janumet has a low risk of weight gain and hypoglycaemia compared with metformin alone and targets all three key defects of diabetes: insulin deficiency from pancreatic beta cells, insulin release, and overproduction of glucose by the liver.

The product is now approved by the 27 member countries of the European Union (EU) to improve glycaemic control in patients with type 2 diabetes inadequately controlled on diet and exercise plus their maximally tolerated dose of metformin alone, or those already being treated with the combination of sitagliptin and metformin. Janumet is also approved for use in combination with a sulphonylurea (SU) as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and an SU. With this approval, Janumet is now approved in more than 50 countries worldwide and more than one million total prescriptions have been dispensed.1 Following marketing authorisation, product launch times may vary from country to country.

The approval of this new combination treatment follows the European Medicines Agency's (EMEA) recent listing of DPP-4 inhibitors, including sitagliptin, as a medicine of notable public health interest.

"We are very pleased to receive European approval of Janumet and the recent recognition by the EMEA of the important role that DPP-4 inhibitors can play in the management of type 2 diabetes. With 53 million people in Europe living with type 2 diabetes, and a substantial proportion not achieving blood glucose goal, this combination provides physicians with an effective new option to help patients manage their blood glucose levels," said Stefan Oschmann, President, Europe, Middle East, Africa and Canada, Merck & Co., Inc.

The combined mechanisms of the two agents in Janumet target all three core defects associated with type 2 diabetes. The sitagliptin component in the combination increases the levels of active incretins, thereby enhancing a natural body process that increases insulin synthesis and release from pancreatic beta cells and lowers glucagon secretion from pancreatic alpha cells, leading to reduced production of glucose by the liver. Metformin, a mainstay of diabetes therapy, targets insulin resistance by increasing the uptake and utilization of glucose. Metformin also decreases production of glucose by the liver in a manner that is complementary to sitagliptin.

Janumet provides powerful glucose lowering

In a 24-week, randomised, double-blind, placebo-controlled study with 701 patients with mildly to moderately elevated HbA1c levels (mean baseline 8.0 percent) inadequately controlled on metformin, patients taking sitagliptin (n=453) experienced a significant additional mean placebo-subtracted reduction in HbA1c of 0.7 percent beyond that achieved by patients who continued on metformin alone (n=224) (p<0.001).

In a 30-week, placebo-controlled clinical study to evaluate the safety and efficacy of the addition of sitagliptin 100 mg once-daily to patients inadequately controlled on metformin (n=190; mean baseline HbA1c 9.2 percent), sitagliptin provided significant improvements in HbA1c levels compared with placebo (p<0.001) at 18 and 30 weeks. In this study, the mean placebo-adjusted HbA1c reduction was -1.0 percent after prior metformin therapy at 18 weeks and continued at 30 weeks. In a subgroup of patients with higher baseline HbA1c( ≥10) percent, the mean placebo-adjusted reduction was -1.8 percent beyond metformin alone at week 18 and, due to improved glycaemia in the placebo group, was -1.4 percent at 30 weeks.

In this 30-week study, the overall incidence of adverse reactions considered as drug- related was similar in the two treatment groups. There were no statistically significant differences between the two treatment groups in the incidence of hypoglycaemia or in the incidence of prespecified gastrointestinal adverse events (abdominal pain, diarrhoea, nausea, vomiting). A small decrease in mean body weight of 0.5 kg was seen in both groups.

The European Commission also reviewed phase III clinical trial results supporting the tolerability and efficacy of sitagliptin 100 mg once-daily in combination with glimepiride (a sulphonylurea) alone or with glimepiride plus metformin.2 Overall, the trial data showed that the addition of sitagliptin significantly reduced HbA1c levels and fasting plasma glucose levels, and was generally well tolerated.2

In the clinical trial in combination with a sulphonylurea (glimepiride) and metformin, sitagliptin demonstrated an overall incidence of adverse reactions higher than that seen with placebo plus glimepiride and metformin, in part related to a higher incidence of hypoglycaemia with the treatment compared to placebo (16.4 percent vs. 0.9 percent, respectively). A higher rate of hypoglycaemia is commonly seen when antihyperglycaemic agents are used in combination with sulphonylurea agents. When sitagliptin is used in combination with a sulphonylurea, a lower dose of the sulphonylurea may be considered to reduce the risk of hypoglycaemia.

The product is not to 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 who are lactating.

Worldwide Availability

More than five million total prescriptions for sitagliptin have been dispensed worldwide since launch.3 Both Janumet and Januvia, the latter approved in the EU in March 2007, offer new treatment options to help a broad range of patients with type 2 diabetes achieve HbA1c goal. Janumet has received approval in more than 50 countries and sitagliptin is approved in more than 70 countries and is available in every region around the world. It is estimated that over 53 million people in Europe have diabetes.4

About Merck & Co., Inc., of Whitehouse Station, N.J., U.S.A.

Merck & Co., Inc. which operates in many countries as Merck Sharp & Dohme or MSD, is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, the Company currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programme that not only donate its medicines but help deliver them to the people who need them. Merck & Co., Inc. also publishes unbiased health information as a not-for-profit service. For more information, visit http://www.merck.com.

Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2007, and in any risk factors or cautionary statements contained in the Company's periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.

References

1 IMS Health, NPATM Weekly, TRxs, week-ending October 20, 2006 through week-ending June 27, 2008.

2 Hermansen K, Kipnes M, Luo E et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin.
Diabetes, Obesity and Metabolism 2007 9(5):733-745.

3 IMS Health, NPATM Weekly, TRxs, week-ending October 20, 2006 through week-ending June 27, 2008.

4 International Diabetes Federation: Diabetes Atlas, 3rd ed. 2006 Chapter 1, p.28.

JANUMETTM is a trademark of Merck & Co., Inc., of Whitehouse St, NJ, USA known in many countries as Merck Sharp & Dohme

Source:
http://www.merck.com