Daily oral safiglipron lowers blood sugar in type 2 diabetes trial

A once-daily tablet lowered blood sugar more effectively than placebo in adults with early type 2 diabetes, according to a phase 3 trial reported by nature.com. The study tested three doses of safiglipron, an oral small-molecule medicine that activates the glucagon-like peptide-1 (GLP-1) receptor, without requiring patients to fast or change when they eat.

After 32 weeks, all three safiglipron groups had significantly greater reductions in glycated haemoglobin (HbA1c) than the placebo group. The placebo-adjusted differences were 1.22 percentage points for the 30-mg dose, 1.20 points for 60 mg and 1.45 points for 90 mg. Each result had a P value below 0.0001.

The findings came from OUTSTAND-1, a randomized, double-blind, placebo-controlled trial conducted across 46 sites in China. It enrolled 284 adults whose diabetes was being managed through diet and exercise alone. Participants were assigned to daily safiglipron at 30 mg, 60 mg or 90 mg, or to placebo, for 32 weeks. The trial then continued with a 20-week period of active treatment, although the reported results focus on the main 32-week assessment.

Blood-sugar improvements across the doses

Participants began the study with an average HbA1c of 7.95%. The median time since their diabetes diagnosis was 1.6 years, indicating a group largely at an early stage of the condition. Women accounted for 33.1% of those enrolled.

By week 32, between 71.4% and 77.8% of people receiving safiglipron had reached an HbA1c below 7%, depending on the dose. The corresponding proportion in the placebo group was 25%. A stricter target of 6.5% or less was reached by 58.6% to 68.1% of participants taking safiglipron, compared with 16.7% receiving placebo.

Fasting plasma glucose also fell more with the study drug. Relative to placebo, the reductions were 1.58 millimoles per litre with 30 mg, 1.68 mmol/l with 60 mg and 2.08 mmol/l with 90 mg. All three comparisons were statistically significant.

The trial found more limited effects on body weight. Compared with placebo, weight differences were a reduction of 0.65% at 30 mg, 2.23% at 60 mg and 3.56% at 90 mg. Other measures generally moved in favour of safiglipron, including post-meal blood glucose, the proportion reaching HbA1c below 5.7%, waist circumference and indicators of insulin sensitivity and pancreatic beta-cell function.

Tolerability and treatment implications

The study also assessed HOMA-β, HOMA-IR and the disposition index, measures used in the trial to examine beta-cell performance, insulin resistance and the relationship between insulin secretion and sensitivity. These outcomes generally favoured safiglipron. Participants taking the drug were also less likely to need rescue treatment.

Insulin and C-peptide responses differed according to the dose. Changes in treatment satisfaction were small, suggesting that the measurable improvements in glucose control did not translate into large shifts in that reported outcome during the study period.

Gastrointestinal problems were the adverse events reported most often. They were generally mild or moderate. Treatment discontinuation occurred in 1.4% of participants assigned to 30 mg, 2.9% of those taking 60 mg and 6.9% of those taking 90 mg. No one in the placebo group stopped treatment because of an adverse event.

The results point to a dose-related pattern in some measures, particularly weight loss and fasting glucose, while HbA1c reductions were substantial at all three doses. Because the participants were managing diabetes with diet and exercise alone, the findings address safiglipron's potential use earlier in the course of treatment.

The investigators concluded that once-daily oral safiglipron could be an effective treatment option for type 2 diabetes. The study is registered on ClinicalTrials.gov under NCT06672172.