Sunday, September 27, 2009

Drug in development: taspoglutide in type 2 diabetes

Taspoglutide, an anti-diabetic drug in late stage development as a prolonged-release injection, was effective in maintaining blood glucose control over the short term in patients with type 2 diabetes when given once weekly or fortnightly.

A number of drugs that target glucagon-like peptide-1 (GLP-1) system have been recently launched or are in development. Two different drug types acting on this system are currently being used researched – the ‘gliptin’ class drugs inhibit the enzyme that degrades endogenous GLP-1 (dipeptidyl peptidase-4, DPP-4), and the GLP-1 analogues that act as agonists resistant to degradation to DPP-4. Taspoglutide is a GLP-4 analogue that has been shown to have anti-diabetic effects: this study tested a prolonged-release formulation suitable for once-weekly dosing. Participants were adults with type 2 diabetes not adequately controlled on metformin 1.5gm daily. They were randomised to receive taspoglutide 5mg, 10mg, or 20mg weekly, or 10mg or 20mg every two weeks, or matching placebo (in addition to their existing dose of metformin). Study duration was eight weeks with an additional four weeks follow-up, and the primary outcome was glycaemic control assessed as haemoglobin A1c (HbA1c) change from baseline one week after eight consecutive weeks of treatment.

A total of 306 patients was randomised to treatment from 572 screened. After nine weeks, HbA1c levels were significantly lower in all the taspoglutide groups compared to placebo. Baseline value was 7.9% (SD ± 0.7%): at assessment, values compared to baseline were -1.0 ± 0.1% (5 mg once weekly), –1.2 ± 0.1% (10 mg once weekly), –1.2 ± 0.1% (20 mg once weekly), –0.9 ± 0.1% (10 mg fortnightly), and –1.0 ± 0.1% (20 mg fortnightly) vs. –0.2 ± 0.1% with placebo. Weight loss, a secondary outcome, was significantly greater than placebo in the 10mg and 20mg weekly groups, and in the 20mg fortnightly group.
Based on their results, the authors conclude that in patients with type 2 diabetes inadequately controlled on metformin, adding taspoglutide to therapy significantly improves glycaemic control. It also improved weight loss in a dose-dependent fashion, and was generally well tolerated.

[Editor’s note: taspoglutide is currently in phase 3 clinical trials – if these are successful, it might be expected to be marketed in around 3 to 4 years time.]

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