Five New Studies and Analyses at Major Medical Meeting Further Demonstrate Substantial Efficacy and Robust Clinical Experience for´JANUVIA´® (sitagliptin)

New data analyses presented at the 44th Annual Meeting of the European Association for the Study of Diabetes (EASD) showed initial combination therapy with the dipeptidyl peptidase–4 (DPP–4) inhibitor, sitagliptin, and metformin provided substantial improvements in blood sugar levels (as measured by HbA1c1) over two years of treatment and was generally well tolerated. Also presented at the meeting was a separate, new pooled analysis of 6,139 patients that shows that sitagliptin 100 mg a day was generally well tolerated in clinical trials of up to two years in duration.

More than six million total prescriptions for sitagliptin have been dispensed worldwide since launch.+ Sitagliptin has received authorisation in 80 countries and is available in every region around the world. The European Medicines Agency (EMEA) licensed sitagliptin in Europe in April 2007 and recently licensed JANUMET++ (sitagliptin/metformin) in July 2008. Sitagliptin is indicated for the treatment of type 2 diabetes to improve glycaemic control in combination with metformin when diet and exercise plus metformin alone do not provide adequate glycaemic control; in combination with a sulphonylurea when diet and exercise plus maximal tolerated dose of a sulphonylurea alone do not provide adequate glycaemic control and when metformin is inappropriate due to contraindications or intolerance; and to improve glycaemic control in combination with a sulphonylurea and metformin when diet and exercise plus dual therapy with these agents do not provide adequate glycaemic control. For patients with type 2 diabetes mellitus in whom use of a PPAR? agonist (i.e. a thiazolidinedione) is appropriate, sitagliptin is indicated in combination with a PPAR? agonist when diet and exercise plus the PPAR? agonist alone do not provide adequate glycaemic control. Sitagliptin# should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Sitagliptin is contraindicated in patients with hypersensitivity to the active substance or to any of the exicipients. The use of sitagliptin in combination with insulin has not been adequately studied.

Initial combination of sitagliptin and metformin provided powerful glycaemic improvements out to two years1

In a study of initial combination therapy with sitagliptin and metformin, glucose–lowering was assessed by measuring the mean change from baseline HbA1c levels at one year and two years. The mean HbA1c reductions from baseline in this study were 1.8 percent at one year (n=153) in patients treated with sitagliptin 50 mg/metformin 1000 mg twice–daily. In the extension study at two years, the mean HbA1c reduction was 1.7 percent (n=105; baseline HbA1c of 8.6 percent) for this group. Additionally, mean HbA1c reductions from baseline were 1.4 percent (at one year, n=147 and two years, n=96) in patients treated with sitagliptin 50 mg/metformin 500 mg twice daily, 1.3 percent (at one year, n=134 and two years, n=87) in patients treated with metformin 1000 mg twice daily, 1.0 percent (at one year, n=117) and 1.1 percent (at two years, n=64) in patients treated with metformin 500 mg twice daily. For patients treated with sitagliptin 100 mg once daily, there was a 0.8 percent reduction in HbA1c levels from baseline at one year (n=106) and a 1.2 percent reduction from baseline at two years (n=50).1

In a subgroup analysis of patients grouped by severity of starting baseline HbA1c, treatment with JANUVIA 50 mg/metformin 1000 mg twice daily demonstrated greater mean HbA1c reductions from baseline in subgroups with higher baseline HbA1c. At one year a mean reduction of 3.1 percent was seen in patients with baseline HbA1c of 10 percent or more (n=17), while reductions of 2.2 percent, 1.7 percent, and 1.0 percent were seen with baseline HbA1c values of nine to 10 percent (n=43), eight to nine percent (n=60), and less than eight percent (n=33), respectively. At two years a mean reduction of 2.5 percent was seen in patients with baseline HbA1c of 9 percent or more (n=38), while reductions of 1.6 percent and 0.9 percent were seen with baseline HbA1c values of greater than or equal to eight to less than nine percent (n=38), and less than eight percent (n=29), respectively.

Three additional studies further demonstrate the safety and efficacy profile of sitagliptin as an add–on to other oral diabetes treatments

In one 52–week study, addition of sitagliptin to the combination of metformin and rosiglitazone* substantially improved glycaemic (blood sugar) control in patients with type 2 diabetes.3 In a separate 52–week study of Japanese patients, treatment with sitagliptin added to ongoing pioglitazone therapy provided effective glycaemic control and was generally well tolerated with a comparable occurrence of hypoglycaemia in the placebo and sitagliptin (50 mg, once daily) groups, and without clinically meaningful change in body weight. A sustained mean reduction in HbA1c from baseline of 0.7 percent was observed; 62 percent of patients achieved HbA1c