SUSTAIN 3 beats exenatide extended-release

A 56-week clinical trial called SUSTAIN 3 found that once-weekly semaglutide, given at the 1.0 mg dose, worked better than exenatide extended-release (ER) at 2.0 mg for people with type 2 diabetes who were not fully controlled on oral diabetes drugs ^[1]. The trial included 813 people randomly assigned to one of the two injectable drugs, and it was open-label, meaning both patients and researchers knew which drug each person was taking ^[1].

At the start of the study, participants had an average HbA1c, a measure of average blood sugar over about three months, of 8.3% ^[1]. After 56 weeks, semaglutide lowered HbA1c by 1.5 percentage points, while exenatide ER lowered it by 0.9 percentage points ^[1]. The difference between the two drugs was statistically significant, meaning it was unlikely to be due to chance ^[1]. More people on semaglutide also reached the common treatment goal of HbA1c below 7.0%: 67% of semaglutide users hit that target compared with 40% of exenatide ER users ^[1].

Weight loss also favored semaglutide. Participants started the trial at an average body weight of 95.8 kilograms, or about 211 pounds ^[1]. Those on semaglutide lost an average of 5.6 kilograms, or about 12.3 pounds, while those on exenatide ER lost 1.9 kilograms, or about 4.2 pounds ^[1]. That means semaglutide users lost roughly three times as much weight as exenatide ER users, matching the summary's headline finding ^[1].

The two drugs had broadly similar safety records, but with some differences in the type of side effects ^[1]. Gastrointestinal problems, such as nausea, were more common with semaglutide, affecting 41.8% of those patients, compared with 33.3% of exenatide ER patients ^[1]. On the other hand, injection-site reactions were far more common with exenatide ER, hitting 22.0% of patients, versus just 1.2% of those on semaglutide ^[1]. The study's authors, writing in a 2017 paper, concluded that semaglutide was "highly effective" for people with type 2 diabetes who were not adequately controlled on oral medications ^[1].

Why it matters for patients

This trial, known as SUSTAIN 3, was one of the studies that helped establish semaglutide's reputation as a strong option for both blood sugar control and weight loss in people with type 2 diabetes, ahead of its various brand launches under names like Ozempic ^[1]. For patients weighing injectable diabetes drugs, the results suggest a tradeoff: semaglutide produced bigger improvements in both blood sugar and weight, but came with a higher chance of gastrointestinal side effects like nausea, while exenatide ER caused more skin reactions where the drug was injected ^[1].

The study does not address longer-term outcomes beyond 56 weeks, cardiovascular effects, or how these results compare to other doses of semaglutide, since only the 1.0 mg dose was tested here ^[1]. It also does not include people using semaglutide for weight loss alone without diabetes, since all participants in this trial had type 2 diabetes ^[1]. Anyone considering these medications would need to look at other evidence for those questions, since this source does not answer them.

What happens next

The trial itself concluded with 56 weeks of data, and its results were published in a peer-reviewed journal, with a follow-up commentary discussing the findings appearing in April 2018 in a separate medical publication ^[1]. The source material provided here does not describe any subsequent updates to this specific trial's data or any changes to drug labeling that followed its publication.