In a pair of company-sponsored clinical trials, oral semaglutide had positive effects on glycemic parameters and weight in patients with type 2 diabetes and on body weight in patients with obesity without type 2 diabetes. The PIONEER PLUS phase 3b trial compared oral semaglutide doses in participants in 14 countries with type 2 diabetes (HbA1c of 8.0–10.5%) and overweight or obesity (BMI of 25 or higher) who were on stable daily doses of 1 to 3 oral glucose-lowering drugs. In the OASIS 1 phase 3 trial, participants with obesity (BMI of at least 30 or at least 27 with comorbidities) and without type 2 diabetes in 9 countries received escalating oral semaglutide doses of up to 50 mg or placebo.
“At baseline, mean (SD) HbA1c was 9.0% (0.8; 74.4 mmol/L [SD 8.3]) and mean bodyweight was 96.4 kg (21.6),” the PIONEER PLUS investigators wrote of 1,606 participants. “Mean changes (SE) in HbA1c at week 52 were −1.5 percentage points (SE 0.05) with oral semaglutide 14 mg, −1.8 percentage points (0.06) with 25 mg (estimated treatment difference [ETD] −0.27, 95% CI −0.42 to −0.12; P = 0.0006), and −2.0 percentage points (0.06) with 50 mg (ETD −0.53, −0.68 to −0.38; P <0.0001). Adverse events were reported by 404 (76%) participants in the oral semaglutide 14 mg group, 422 (79%) in the 25 mg group, and 428 (80%) in the 50 mg group. Gastrointestinal disorders, which were mostly mild to moderate, occurred more frequently with oral semaglutide 25 mg and 50 mg than with 14 mg. Ten deaths occurred during the trial; none were judged to be treatment related.”
For the 667 participants in OASIS 1 trial, the authors found the “estimated mean bodyweight change from baseline to week 68 was –15.1% (SE 0.5) with oral semaglutide 50 mg versus –2.4% (0.5) with placebo (estimated treatment difference −12.7 percentage points, 95% CI −14.2 to −11.3; P <0.0001). More participants reached bodyweight reductions of at least 5% (269 [85%] of 317 vs 76 [26%] of 295; odds ratio [OR] 12.6, 95% CI 8.5 to 18.7; P <0.0001), 10% (220 [69%] vs 35 [12%]; OR 14.7, 9.6 to 22.6), 15% (170 [54%] vs 17 [6%]; OR 17.9, 10.4 to 30.7), and 20% (107 [34%] vs 8 [3%]; OR 18.5, 8.8 to 38.9) at week 68 with oral semaglutide 50 mg versus placebo. Adverse events were more frequent with oral semaglutide 50 mg (307 [92%] of 334) than with placebo (285 [86%] of 333). Gastrointestinal adverse events (mostly mild to moderate) were reported in 268 (80%) participants with oral semaglutide 50 mg and 154 (46%) with placebo.”