Summary
In a 284-person phase 3 trial in China, once-daily oral safiglipron lowered HbA1c more than placebo over 32 weeks in adults with early type 2 diabetes. Gastrointestinal adverse events were common and increased with dose.
A phase 3 trial in China found that once-daily oral safiglipron reduced blood glucose in adults with early type 2 diabetes more than placebo over 32 weeks. The randomized, double-blind study tested three doses of the small-molecule GLP-1 receptor agonist in 284 adults whose diabetes was being managed with diet and exercise alone. Safiglipron can be taken without fasting or food-related dosing restrictions, according to the study.
HbA1c fell across all three doses
The trial’s primary outcome was change in HbA1c, a measure of average blood glucose over the preceding few months. At week 32, HbA1c was lower than with placebo by 1.22 percentage points with 30 mg safiglipron, 1.20 points with 60 mg and 1.45 points with 90 mg. All three comparisons had P values below 0.0001. The study was conducted at 46 sites in China, and participants took their assigned treatment once daily.
More participants receiving safiglipron reached the HbA1c target of below 7.0%: 71.4–77.8% across the dose groups, compared with 25.0% on placebo. Fasting blood glucose also fell more with each safiglipron dose than with placebo.
Weight changes were smaller than the glucose effects and varied by dose. Compared with placebo, the estimated weight differences were −0.65% with 30 mg, −2.23% with 60 mg and −3.56% with 90 mg. The 30 mg difference was not statistically significant (P = 0.21); the differences at 60 mg and 90 mg were statistically significant.
Safiglipron, also identified in the paper as HRS-7535, is a small-molecule drug that activates the GLP-1 receptor. GLP-1 receptor agonists help regulate blood glucose, including by promoting insulin release when glucose is elevated. Participants assigned to the 60 mg and 90 mg doses began at 30 mg, with increases in 30 mg steps every four weeks.
Gastrointestinal events were the most common side effects
During the 32-week placebo-controlled period, gastrointestinal adverse events were reported in 44.3% of participants taking 30 mg, 60.0% taking 60 mg and 73.6% taking 90 mg, compared with 15.3% on placebo. Most were mild or moderate and occurred during dose titration. Adverse events led to treatment discontinuation in 1.4%, 2.9% and 6.9% of participants in the three safiglipron groups, respectively, and none in the placebo group. Serious adverse events were reported in all groups; no deaths or severe hypoglycaemia occurred.
The study followed participants for 52 weeks, but the placebo comparison lasted 32 weeks. From week 33, participants originally assigned to placebo switched to safiglipron 30 mg. The researchers reported that improvements remained evident at week 52, alongside some easing of the HbA1c reduction and partial weight regain, but the extension did not provide a continuing placebo comparison.
The results apply to a specific patient group
Participants were all Asian and had a median diabetes duration of 1.6 years. They were not taking glucose-lowering medication during the period before the trial, although about one-third had used such medication previously. The findings therefore describe safiglipron used alone in a relatively early-disease population, rather than its effects in people taking other diabetes medicines or in populations with different characteristics.
The trial provides phase 3 evidence that safiglipron can improve glycaemic control in this setting. Longer-term follow-up, including study of whether on-treatment changes persist after treatment stops, will be needed to assess the durability of these effects.