Oral semaglutide reduces HbA1c and body weight more than other oral antidiabetic agents |
Oral semaglutide induces comparable reductions in HbA1c and body weight with injectable glucagon-like peptide-1 receptor agonists |
The safety profile of oral semaglutide is also similar with injectable glucagon-like peptide-1 receptor agonists |
Introduction
Methods
Pharmacology of Oral Semaglutide
Study | Ref | n | Follow-up (weeks) | Baseline treatment | Comparator drug | Dosage of semaglutide | Major findings |
---|---|---|---|---|---|---|---|
PIONEER-1 | 13 | 703 | 26 | Diet and exercise alone | 3, 7 or 14 mg/day | Semaglutide reduced HbA1c and weight by 0.7–1.4% and 0.2–2.6 kg more than placebo, respectively Treatment discontinuation: 2.3–7.4% and 2.2%, respectively | |
PIONEER-8 | 18 | 731 | 52 | Insulin with or without metformin | 3, 7 or 14 mg/day | Semaglutide reduced HbA1c and weight by 0.5–1.2% and 0.9–3.3 kg more than placebo, respectively Nausea: 1.6–3.3 times more frequent in the semaglutide arm | |
PIONEER-7 | 14 | 504 | 52 | 1–2 oral antidiabetic agents | Sitagliptin 100 mg/day | 3, 7 or 14 mg/day | More patients achieved HbA1c levels < 7% in the semaglutide group (63 vs. 28% in the sitagliptin group) and mean weight loss was 2.2 kg greater in the former |
PIONEER-3 | 16 | 1864 | 78 | Metformin with or without sulfonylurea | Sitagliptin 100 mg/day | 3, 7 or 14 mg/day | Semaglutide 7 and 14 mg/day reduced HbA1c and weight more than sitagliptin (by 0.3 and 0.7%, respectively, and by 1.6 and 2.4 kg, respectively) Treatment discontinuation rates: 15.0, 19.1 and 13.1%, respectively |
PIONEER-2 | 17 | 822 | 52 | Metformin | Empagliflozin 25 mg/day | 14 mg/day | Semaglutide reduced HbA1c and body weight by 0.4% and 0.9 kg more than empaglifozin, respectively Gastrointestinal adverse events were more common with semaglutide |
PIONEER-4 | 15 | 711 | 52 | Metformin with or without a SGLT-2 inhibitor | Liraglutide (dose escalated to 1.8 mg/day) | Up to 14 mg/day | Semaglutide reduced HbA1c by 0.2 and 1.2% more than liraglutide and placebo, respectively, and body weight by 1.5 and 4.0 kg more than liraglutide and placebo, respectively Rates of adverse events were similar in the semaglutide and liraglutide group and lower in the placebo group |
PIONEER-5a | 19 | 324 | 26 | Metformin or sulfonylurea, or both, or basal insulin with or without metformin | Up to 14 mg/day | Semaglutide reduced HbA1c and weight by 1.1% and 3.7 kg more than placebo, respectively Treatment discontinuation due to adverse events: 15 and 5%, respectively | |
PIONEER-9b | 20 | 243 | 52 | Liraglutide 0.75 mg/day | 14 mg/day | Semaglutide and liraglutide induced similar reductions in HbA1c (1.7 and 1.4%, respectively) Constipation, which was the most frequent adverse event, occurred in 13 and 19% of patients, respectively | |
PIONEER-10b | 21 | 458 | 52 | Once-weekly dulaglutide 0.75 mg | 14 mg/day | Semaglutide 14 mg/day induced greater reductions in HbA1c (1.7 vs. 1.4%, respectively) and in weight (− 1.6 vs. 1.0 kg, respectively) Rates of adverse events leading to treatment discontinuation: 6 and 3%, respectively |