The following is a sample created for personal use, in which the same article was summarized for two audiences. The first is intended for a physician audience, and the second is a short summary for the general public.

The summarized article: Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study

Both once-daily liraglutide and once-weekly exenatide offer effective glycemic control and weight loss when prescribed to those with type 2 diabetes, although the benefits (and also side effects) are greater in those who receive liraglutide, according to a study published in The Lancet. 1

The class of antihyperglycemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists, have shown promise for patients with type 2 diabetes due to their ability to stimulate glucose-dependent insulin secretion, reduce glucagon secretion, slow gastric emptying, and decrease food intake.

Prior studies have shown that twice-daily injections of exenatide––the first approved GLP-1 receptor agonist––decreased fasting and post-prandial glucose concentrations, reduced body weight, and improved glycemic control. 2-5 Since then, exenatide has been developed into a once-weekly formulation and approved for use in patients with type 2 diabetes. An alternative GLP-1 receptor agonist for those with type 2 diabetes is liraglutide, which comes in a once-daily format.

Research has shown that liraglutide and once-weekly exenatide produce better glycemic control than twice-daily exenatide,6 but Buse et al. completed the first comparative study between once-daily liraglutide and once-weekly exenatide.

For the study, the researchers conducted a 26-week, open-label, randomized study at 105 sites spanning 19 countries. Patients eligible for the study had type 2 diabetes, were at least 18 years old, and had inadequate glycemic control despite diet and exercise lifestyle changes and oral antihyperglycemic drugs at maximum or near-maximum doses. After a week-long screening period, the patients were randomly assigned to receive daily injections of liraglutide or once-weekly exenatide.

All patients saw a similar decline in blood pressure alongside improvements in the cardiovascular biomarker brain natriuretic peptide. Both drugs also showed a decrease in HbA1c compared to baseline recordings, although the change in HbA1c from endpoint to baseline was greater in the patients taking liraglutide compared to those taking exenatide. Furthermore, while both treatments were associated with a loss of body weight and a decrease in fasting serum glucose, these declines were also greater in the patients taking liraglutide.

Surprisingly, these findings do not match the researcher’s initial predictions, with them expecting exenatide to have a greater effect on glycemic control and weight loss than liraglutide because of studies that compared these treatments with other oral antidiabetic drugs. Some possible reasons for this study’s unexpected findings include the study population, pharmacological exposure, or study design, although the true reason remains unknown.

As for adverse events, the most common for both groups were gastrointestinal, with the liraglutide group seeing a greater frequency of diarrhea, nausea, and vomiting. For both groups, the frequency of these events was greater at the beginning of the treatment and then decreased in incidence over time. However, 24 (5%) of the patients in the liraglutide group discontinued treatment due to these adverse events, whereas only 12 (3%) patients from the exenatide group opted to stop treatment.

While the liraglutide group experienced more mild gastrointestinal adverse events, the researchers noted more serious adverse events in the exenatide group, although there was no distinguishable pattern to the events.

Of note, a limitation of the study is its open-label design, which was chosen because of the unavailability of once-daily liraglutide as a placebo. However, the open-label design may have influenced patients’ expectations. Furthermore, the lack of systematically obtained pharmacokinetic data limits the ability of the research team to assess the reasoning behind their findings.

Despite these limitations, this study serves as the first direct comparison between the efficacy and safety of two GLP-1 receptor agonists used to treat type 2 diabetes. The findings by Buse et al. show that both treatments improved glycemic control and promoted weight loss, although these results were greater in those receiving liraglutide compared to exenatide. These benefits also come at a cost, with the liraglutide group seeing increased gastrointestinal side effects.

Overall, the information gained from this study regarding the efficacy and safety comparisons of liraglutide and exenatide can further improve clinical decision-making for patients with uncontrolled type 2 diabetes, especially those unresponsive to antihyperglycemic drugs.

1. Buse JB, Nauck M, Forst T, et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet. 2013;381(9861):117-124. doi:10.1016/S0140-6736(12)61267-7

2. Buse JB, Henry RR, Han J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004;27(11):2628-2635. doi:10.2337/diacare.27.11.2628

3. DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005;28(5):1092-1100. doi:10.2337/diacare.28.5.1092

4. Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005;28(5):1083-1091. doi:10.2337/diacare.28.5.1083

5. Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin. 2008;24(1):275-286. doi:10.1185/030079908x253870

6. Drucker DJ, Buse JB, Taylor K, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008;372(9645):1240-1250. doi:10.1016/S0140-6736(08)61206-4

Researchers have placed liraglutide and exenatide––two treatments intended for those with type 2 diabetes––head-to-head regarding their safety and effectiveness. 1

For the study, eligible patients had to be above 18 years of age with type 2 diabetes. Additionally, the participants needed to have poor blood sugar control despite making lifestyle changes and taking appropriate medication. Once the researchers screened the eligible patients, they were divided into two groups: one receiving once-daily liraglutide and the other receiving once-weekly exenatide.

Based on previous studies comparing each treatment with other antidiabetic drugs, the researchers expected exenatide to have greater results, but their findings were surprising.

When it came to the drug’s ability to control blood sugar levels and promote weight loss, both drugs were effective, but liraglutide saw greater results. However, this came at the expense of greater gastrointestinal side effects such as nausea, diarrhea, and vomiting. In most cases, these side effects were mild in both treatment groups, but 5% of the liraglutide group and 3% of the exenatide group decided to opt out of the study because of them.

The results of this head-to-head comparison show that both liraglutide and exenatide can help improve blood sugar levels in those with type 2 diabetes, but liraglutide can be a bit more effective than exenatide. Still, the results of this study can help doctors make better clinical decisions when treating someone with type 2 diabetes whose other medications are not working.

1.  Buse JB, Nauck M, Forst T, et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet. 2013;381(9861):117-124. doi:10.1016/S0140-6736(12)61267-7