Januvia - novel oral hypoglycaemia agent

MSD has launched Januvia (sitagliptin) indicated for use with metformin or a glitazone for type II diabetes inadequately controlled by diet, exercise and either metformin or a glitazone alone.

PHARMACOLOGY
Sitagliptin is a dipeptidyl peptidase-4 inhibitor, a new class of oral hypoglycaemic agents. The improvement in glycaemic control observed with sitagliptin may be mediated through enhancement of active incretin hormone levels. The incretins are part of an endogenous system involved in the regulation of glucose homeostasis.

CLINICAL STUDIES
The efficacy of sitagliptin was compared to metformin, pioglitazone and glipizide therapy. A 24-week study1 in 701 patients assessed the efficacy of sitagliptin in patients with inadequate glycaemic control (HbA1c >7 and <10 per cent) with metformin (>1500 mg/day) alone.  Patients remained on metformin therapy and were randomised to receive sitagliptin or placebo. Patients exceeding specific glycaemic limits during the 24-week treatment period were provided with pioglitazone rescue therapy until the end of the study.

At week 24, there was a significant reduction in HbA1c in the sitagliptin 100mg once daily group compared with placebo. The placebo subtracted reduction from baseline in HbA1c for the sitagliptin group was -0.65 per cent.
There was a significant increase in the proportion of patients achieving an HbA1c <7 per cent with sitagliptin compared with placebo; 47 per cent versus 18.3 per cent in the siatgliptin and placebo groups, respectively.
There were no significant differences in the incidence of either hypoglycaemia or predefined gastrointestinal adverse effects between the sitagliptin and placebo groups.

The efficacy of sitagliptin added to ongoing pioglitazone therapy was studied in patients with inadequate glycaemic control (HbA1c >7 and <10 per cent) on a stable dose of pioglitazone.2 Patients were randomised to receive sitagliptin 100mg once daily or placebo for 24 weeks. The primary efficacy endpoint was the change from baseline in HbA1c at week 24.

There was a significant reduction in HbA1c  in the sitagliptin group, compared with baseline and placebo. The between-treatment difference in percentage change from baseline in HbA1c  was -0.7 per cent. There was a significant increase in the proportion of patients attaining HbA1c values <7 per cent compared with placebo (45.4 per cent versus 23.0 per cent, respectively). The incidence of adverse effects was similar between sitagliptin and placebo.

A 52-week study3 compared the efficacy of sitagliptin versus glipizide in patients with inadequate glycaemic control (HbA1c >6.5 and <10 per cent) on metformin alone. Patients were randomised to receive sitagliptin 100mg once daily (n=382) or glipizide (n=411). The mean HbA1c change at week 52 was -0.67 per cent in both the sitagliptin and the glipizide treatment groups. There was no significant difference in the percentage of patients with an
HbA1c <7 per cent at week 52 between the sitagliptin and the glipizide groups (63 per cent and 59 per cent, respectively).

1. Charbonnel B, Karasik A, Liu J et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type II diabetes inadequately controlled with metformin alone. Diabetes Care 2006: Vol 29 (12); 2638-2643.
2. Rosenstock
J, Brazg R, Andryuk P et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type II diabetes: a 24-week, multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Clinical Therapeutics 2006: Vol 28 (10); 1556-1568.
3. Nauck M, Meininger G, Sheng D et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulphonylurea, glipizide, in patients with type II diabetes inadequately controlled on metformin alone: a randomised, double-blind, non-inferiority trial. Diabetes, Obesity and Metabolism 2007: 9; 194-205.

Further information: MSD 01992 467272

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