DURATION-2 study has shown that a once-weekly injection of Exenatide ( Bydureon ) in patients with type 2 diabetes mellitus was more effective at improving blood sugar control and inducing weight loss than were either daily oral Sitagliptin ( Januvia ) or Pioglitazone ( Actos ).

Most patients with type 2 diabetes who need drug treatment begin on Metformin, but eventually need additional treatment.
The DURATION-2 study compared three drugs with different mechanisms of action: once-weekly injected Exenatide, daily oral Sitagliptin, and daily oral Pioglitazone.

In this 26-week randomised trial, the patients included all had type 2 diabetes and had been treated with Metformin.
The mean baseline glycosylated haemoglobin ( HbA1c ) concentration in the cohort was 8.5%, the mean fasting plasma glucose was 9.1 mmol/L, and the mean bodyweight was 88 kg.
The study included patients from the USA, India, and Mexico.

Patients were randomly assigned to Exenatide 2mg injected once weekly plus daily oral placebo ( 170 patients ); daily oral Sitagliptin 100 mg plus placebo injected once weekly ( 172 ); or daily oral Pioglitazone plus placebo injected once weekly ( 172 ). All patients continued their Metformin treatment throughout the study.

A total of 491 patients received at least one dose of the study drug and were included in the final analysis ( 160 Exenatide, 166 Sitagliptin, 165 Pioglitazone ).
Treatment with Exenatide reduced HbA1c by 1.5%, compared with 0.9% in the Sitagliptin group and 1.2% in the Pioglitazone group.

Patients in the Exenatide group lost on average 2.3 kg, compared with a mean weight loss of 0•8kg in the sitagliptin group and a mean weight gain of 2.8 kg in the Pioglitazone group.

No major episodes of hypoglycaemia occurred in any group. The most frequent adverse events with Exenatide and Sitagliptin were nausea ( 24% and 10%, respectively ) and diarrhoea ( 18% and 10% respectively ); while upper respiratory tract infection ( 10% ) and peripheral oedema ( fluid retention/swelling in the legs ) ( 8% ), were the most frequent events with Pioglitazone.

According to authors, the improvements in HbA1c and bodyweight with once-weekly Exenatide suggest that this drug should be considered as an adjunct to Metformin in patients needing improvements in glucose control and bodyweight, and in whom the risk of hypoglycaemia needs to be kept to a minimum.

Source: Lancet, 2010

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