In DURATION-2, presented this week at the annual meeting of the American Diabetes Association and published in the Lancet, 491 type 2 diabetics were randomized for 26 weeks to once-weekly exenatide, sitagliptin, or piolgitazone. Exenatide treatment resulted in a significantly greater reduction in HbA1c than either sitagliptin or pioglitazone. Weight loss was also significantly greater in the exenatide-treated group. The main drawback to the drug was nausea and diarrhea. The authors concluded:
Although long-term outcome studies of GLP-1-related therapies are needed, our study provides one of the most comprehensive direct comparisons of key intermediate outcome markers with adjunctive treatments to metformin. 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.
Here is the press release from the Lancet:
ONCE-WEEKLY EXENATIDE INJECTION IMPROVES BLOOD SUGAR CONTROL MORE THAN DAILY ORAL SITAGLIPTIN OR PIOGLITAZONE AND INDUCES MORE WEIGHT LOSS (DURATION-2 study)
A convenient, once-weekly injection of exenatide in patients with type 2 diabetes was more effective at improving blood sugar control and inducing weight loss than were either daily oral sitagliptin or pioglitazone. The findings of the DURATION-2 study are published Online First by The Lancet to coincide with presentation at the American Diabetes Association meeting in Florida, USA. The Article is written by Dr Richard M Bergenstal, International Diabetes Center at Park Nicollet, Minneapolis, MN, USA, and colleagues, for the DURATION-2 Study Group.
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 88·0kg. 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 100mg 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.
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 2·3kg, compared with a mean weight loss of 0·8kg in the sitagliptin group and a mean weight gain of 2·8kg in the pioglitazone group. No major episodes of hypoglycaemia (abnormally low blood sugar) 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.
The authors say: “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.”
They conclude: “The goal of many clinicians who manage diabetes is to achieve optimum glucose control alongside weight loss and a minimum number of hypoglycaemic episodes. Addition of exenatide once weekly to metformin achieved this goal more often than did addition of maximum daily doses of either sitagliptin or pioglitazone.”
In an accompanying Comment, Dr Michael A Nauck, Diabeteszentrum Bad Lauterberg, MeierBad Lauterberg im Harz, Germany, and Dr Juris J Meier, St Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Bochum, Germany, say that in the future, choice of specific anti-diabetic treatments “will be determined by individual patient characteristics and personal preferences, perhaps with the assistance of pharmacogenomic profiles”.
