SUSTAIN 1 published: first phase 3 semaglutide results

A study published on January 17, 2017, reported the first phase 3 results for semaglutide, the drug that would later become known under the brand names Ozempic and Wegovy ^[1]. The trial, called SUSTAIN 1, tested once-weekly semaglutide against placebo in people with type 2 diabetes who had not yet used any diabetes medication ^[1].

Researchers enrolled 388 adults at 72 sites in eight countries, including the United States, between February and August 2014 ^[1]. Participants had been managing their diabetes with diet and exercise alone and had a starting average blood sugar level, measured as HbA1c, of 8.05% ^[1]. They were randomly assigned to receive a weekly injection of either 0.5 mg or 1.0 mg of semaglutide, or a matching placebo, for 30 weeks ^[1].

By the end of the trial, people on the 0.5 mg dose saw their HbA1c fall by 1.45 percentage points, and those on the 1.0 mg dose fell by 1.55 percentage points ^[1]. The placebo group barely moved, dropping just 0.02 percentage points, a change the study authors called not statistically significant ^[1]. Both semaglutide doses beat placebo by a wide margin, with differences of about 1.43 and 1.53 percentage points, and the results were highly significant statistically (p<0.0001 for both) ^[1].

Body weight told a similar story. Starting from an average weight of about 92 kg (roughly 203 pounds), participants on 0.5 mg lost 3.73 kg (about 8.2 pounds) and those on 1.0 mg lost 4.53 kg (about 10 pounds), compared with just 0.98 kg (about 2.2 pounds) on placebo ^[1]. Weight loss was a secondary measure in this trial, not the main goal, since the study was designed and run as a diabetes trial ^[1].

Side effects followed a pattern that has since become familiar to semaglutide users. Nausea was reported by 20% of people on the lower dose and 24% on the higher dose, compared with 8% on placebo ^[1]. Diarrhea affected 13% and 11% of the two semaglutide groups, versus 2% on placebo ^[1]. These gastrointestinal issues were the main reason people dropped out of the study, with discontinuation rates of 13%, 12%, and 11% across the 0.5 mg, 1.0 mg, and placebo groups respectively ^[1]. No deaths occurred in any group, and the study authors described most side effects as mild or moderate ^[1].

Why it matters for patients

This trial, funded by Novo Nordisk, the maker of semaglutide, was the foundation study that helped establish semaglutide as a treatment option for type 2 diabetes before it was later approved and marketed under different names and doses for weight loss ^[1]. For patients today taking Ozempic, Wegovy, or Rybelsus, this early data offers a baseline picture: even before higher doses were tested, semaglutide produced meaningful drops in blood sugar and modest weight loss compared with no active treatment ^[1].

The gastrointestinal side effects seen here, nausea and diarrhea in particular, appeared early and have remained a consistent feature of semaglutide treatment in later, larger trials. Patients considering these drugs may find it useful to know that these effects were common enough in this founding trial to be the leading cause of people stopping the medication ^[1].

It is worth noting this trial was short, just 30 weeks, and included a relatively small group of 387 people who actually received treatment ^[1]. It also tested semaglutide only as a first medication for people not yet using any other diabetes drug, which does not reflect how many patients use it today, often alongside other treatments or specifically for weight management ^[1]. Longer-term safety and effectiveness data came from later studies not covered here.