Semaglutide might be a key for breaking the vicious cycle of metabolically associated fatty liver disease spectrum?

Table 3 Completed studies with oral semaglutide and their main conclusions

Study	Ref.	Main conclusion
PIONEER 1	Aroda et al[57], 2019	Oral semaglutide monotherapy demonstrated superior and clinically relevant improvements in HbA1c (all doses) and body weight loss (14 mg dose) versus placebo
PIONEER 2	Rodbard et al[58], 2019	Oral semaglutide was superior to empagliflozin in reducing HbA1c but not body weight at 26 wk in T2DM patients uncontrolled on metformin. At week 52, HbA1c and body weight (trial product estimand) were significantly reduced versus empagliflozin
PIONEER 3	Rosenstock et al[59], 2019	Oral semaglutide, 7 mg/d and 14 mg/d, compared with sitagliptin, resulted in significantly greater reductions in HbA1c over 26 wk
PIONEER 4	Pratley et al[60], 2019	Oral semaglutide was non-inferior to subcutaneous liraglutide and superior to placebo in decreasing HbA1c, and superior in decreasing body weight compared with both liraglutide and placebo at week 26
PIONEER 5	Mosenzon et al[61], 2019	Oral semaglutide was effective in patients with type 2 diabetes and moderate renal impairment
PIONEER 61	Husain et al[62], 2019	The cardiovascular risk profile of oral semaglutide was not inferior to that of placebo in high CV risk T2DM patients
PIONEER 7	Pieber et al[63], 2019	Superior glycemic control and weight loss with once-daily oral semaglutide with flexible dose adjustment versus sitagliptin 100 mg in type 2 diabetes
PIONEER 7 EXTENSION	Buse et al[64], 2020	Switching from sitagliptin to flexibly dosed oral semaglutide maintained HbA1c reductions, helped more patients achieve HbA1c targets with less use of additional glucose-lowering medication, and offers the potential for additional reductions in body weight
PIONEER 8	Zinman et al[65], 2019	Oral semaglutide was superior to placebo in reducing HbA1c and body weight when added to insulin with or without metformin in patients with T2DM
PIONEER 9	Yamada et al[66], 2020	Oral semaglutide provides significant reductions in HbA1c compared with placebo in a dose-dependent manner in Japanese patients with T2DM
PIONEER 10	Yabe et al[67], 2020	Once-daily oral semaglutide reduced HbA1c and bodyweight vs weekly dulaglutide 0.75 µg in Japanese T2DM patients

¹Cardiovascular safety study. CV: Cardiovascular; T2DM: Type 2 diabetes mellitus; HbA1c: Hemoglobin A1c.