In the Phase II studies of more than 1,000 patients, ''sitagliptin'', Merck Sharp & Dohme's investigational medicine from a new class of diabetes treatments called dipeptidyl peptidase 4 (DPP-4) inhibitors, improved glycaemic control in patients with type 2 diabetes and exhibited a safety and tolerability profile similar to placebo. In addition, patients taking sitagliptin experienced no significant weight gain and a low risk of hypoglycaemia.
"Results from the studies conducted to date are very promising," said Peter Stein, Senior Director in Clinical Research, Metabolism, Merck Research Laboratories, Rahway, NJ, USA. "The need for well tolerated therapies which achieve better glycaemic control than current therapies is well known and we are confident that these short-term clinical studies demonstrate proof of concept for sitagliptin, offering a new hope for type 2 diabetes patients. Ongoing Phase III trials should provide greater insight into the efficacy and tolerability profile of sitagliptin over a longer period of time".
Study 1: Effect of sitagliptin oral tablets on glycaemic control
Results from a 12-week, double-blind, placebo-controlled, parallel group study in patients with type 2 diabetes showed that sitagliptin oral tablets significantly reduced HbA1c (A1C) from baseline as compared to placebo with an average reduction of 0.6 percent observed in the sitagliptin 100 mg once daily group (p<.001).
The majority of the patients in this study had mild to moderate hyperglycaemia. The mean baseline A1C was approximately 7.7 with 28.8 percent of patients having a baseline A1C at or less than 7.0 percent. Observed differences in A1C between patients taking sitagliptin and patients administered placebo were greatest in those patients with a higher baseline A1C at randomization. In patients with a higher A1C baseline (i.e., between 8.5 and 10 percent), a 0.8 percent reduction, relative to placebo, was seen in patients randomized to the 100 mg once daily dose of sitagliptin using data carried forward, that is including patients whether they completed the study or not. A mean 1.1 percent reduction in A1C relative to placebo was observed in patients taking sitagliptin using data from patients who completed the study as per study protocol.
In this study, 552 type 2 diabetes patients, aged 30-74 years and with an HbA1C of 5.8 – 10.4% were randomized to one of five treatment groups: Placebo; sitagliptin (25 mg, 50 mg, or 100 mg) oral tablets once daily; or sitagliptin 50 mg oral tablets twice daily. Treatment with sitagliptin was generally well tolerated and resulted in no significant weight gain or incidence of GI related adverse events. Only one adverse event of hypoglycaemia was reported in each of the four sitagliptin treatment groups, compared to no adverse events of hypoglycaemia reported in the placebo group.
Study 2: Efficacy and tolerability of sitagliptin
The second study presented was a randomized, double-blind, placebo-controlled study, which evaluated the efficacy and tolerability of sitagliptin in 743 patients with type 2 diabetes. The majority of the patients in this study had mild to moderate hyperglycaemia (mean baseline A1C of 7.8 - 7.9 percent). Patients were randomized to one of six treatment groups: placebo; sitagliptin (5mg, 12.5 mg, 25 mg, or 50 mg oral tablets twice daily); or the sulfonylurea, glipizide, 5 mg titrated to 20 mg. After a 12 week treatment period, sitagliptin significantly reduced A1C from baseline compared to placebo. The largest reduction in the patients treated with sitagliptin was 0.77 percent p<0.001, in the 50 mg twice-daily treatment group. Patients taking glipizide showed a 1.0 percent reduction from baseline in A1C. In the active treatment groups, placebo subtracted A1C results did not appear to reach a plateau.
Treatment with sitagliptin was generally well tolerated and resulted in no significant weight gain. Patients treated with glipizide had an average weight gain of 1.1 kilogram relative to placebo. Adverse event reports of hypoglycaemia were observed in 4 percent of patients taking sitagliptin, 17 percent of patients taking glipizide and 2 percent of patients taking placebo.
"The loss of efficacy with sulfonylureas is well described. Longer term studies with an appropriate once daily dose of sitagliptin will address the full efficacy and potential durability of sitagliptin versus glipizide," commented Russell Scott MD, PhD, Professor of Medicine, Director of Diabetes and Lipid Research Group, Christchurch Hospital and School of Medicine, New Zealand.
About sitagliptin
Sitagliptin is an investigational medicine now under development by Merck & Co. for the treatment of type 2 diabetes. If approved, sitagliptin would be a member of a new class of antihyperglycaemic agents called DPP-IV inhibitors, which inhibit the DPP-4 enzyme that normally inactivates the incretin gut hormones GLP-1 and GIP. Sitagliptin is expected to lower blood glucose levels by increasing the level of active incretin hormones which increase insulin from pancreatic beta-cells and decrease glucagon from pancreatic alpha cells in a glucose-dependent manner (when blood glucose is elevated and not when blood glucose is low).
About Merck
Merck & Co., Inc., which operates in many countries as Merck Sharp & Dohme (MSD), is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines in more than 20 therapeutic categories. The company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.
Forwarding-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 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 cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2004, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.
References
1. The International Diabetes Federation (www.idf.org)
2. The International Diabetes Federation (www.idf.org)
3. The International Diabetes Federation (www.idf.org)