Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme

Abstract

Aims: To evaluate the efficacy and safety of oral semaglutide versus comparators by patient characteristic subgroups in patients with type 2 diabetes.

Materials and methods: Change from baseline in glycated haemoglobin (HbA1c) and body weight, and achievement of HbA1c <7.0% with oral semaglutide 7 mg, oral semaglutide 14 mg, flexibly dosed oral semaglutide (flex) and comparators were assessed across baseline subgroups (age, race, ethnicity, diabetes duration, body mass index and HbA1c) from the PIONEER programme. Treatment differences were analysed using a mixed model for repeated measurements for continuous variables and a logistic regression model for the binary endpoint. Pooled safety data were analysed descriptively.

Results: Changes from baseline in HbA1c and body weight, and the odds of achieving HbA1c <7.0%, were greater with oral semaglutide 14 mg/flex (n = 1934) and higher or similar with oral semaglutide 7 mg (n = 823) versus comparators (n = 2077) across most subgroups. Changes in HbA1c with oral semaglutide 14 mg/flex were greater for patients with higher baseline HbA1c (HbA1c >9.0%: -1.7% to -2.6%; HbA1c <8.0%: -0.7% to -1.2%). In some trials, Asian patients experienced greater HbA1c reductions with oral semaglutide 14 mg/flex (-1.5% to -1.8%) than other racial groups (-0.6% to -1.6%). The overall incidence of adverse events (AEs) with oral semaglutide was similar to that with comparators and was consistent across subgroups. More gastrointestinal AEs were observed with oral semaglutide, versus comparators, across subgroups.

Conclusions: Oral semaglutide demonstrated consistently greater HbA1c and body weight reductions across a range of patient characteristics, with greater HbA1c reductions seen at higher baseline HbA1c levels.

Keywords: GLP-1 analogue; antidiabetic drug; glycaemic control; incretin therapy; type 2 diabetes; weight control.

Conflict of interest statement

V.R.A. reports receiving consultancy fees from Applied Therapeutics, Fractyl, Novo Nordisk A/S, Pfizer and Sanofi, and research grant support (to institution) from Applied Therapeutics/Medpace; Eli Lilly; Premier/Fractyl, Novo Nordisk and Sanofi/Medpace. V.R.A.'s spouse is employed by Janssen. E.M. reports scientific advisory board, consulting, lecturing and/or research grants from AstraZeneca, Menarini, Merck Sharp & Dohme, Novo Nordisk and Sanofi. M.H. has served as an advisory board member for AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Novo Nordisk and Sanofi; a speaker for AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Mundipharma, Novartis, Novo Nordisk and Sanofi; and received research support from Eli Lilly and Sanofi. J.R. has served on advisory panels for Applied Therapeutics, Boehringer Ingelheim, Eli Lilly, Intarcia, Novo Nordisk, Oramed, Sanofi and Zealand, and has received research support from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, GlaxoSmithKline, Intarcia, Janssen, Lexicon, Merck and company, Novo Nordisk, Oramed, Pfizer and Sanofi. J.J.M. has received grants from Merck and company, Novo Nordisk and Sanofi, and lecture/other fees from AstraZeneca, Boehringer Ingelheim, Bristol‐Myers Squibb, Eli Lilly, Merck and company, Novo Nordisk, Sanofi and Servier. R.B., E.C. and K.K. are employees of Novo Nordisk. R.B. and E.C are shareholders in Novo Nordisk.

© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Change from baseline in A, glycated haemoglobin (HbA1c), and B, body weight, by baseline age. Abbreviations: flex, flexibly dosed; OAD, oral antidiabetes drug; SGLT2i, sodium‐glucose cotransporter‐2 inhibitor; SU, sulphonylurea. †Including metformin, an SU, an SGLT2i or a thiazolidinedione. Analyses were conducted at the end of treatment on data from the full analysis set using the trial product estimand. The P value indicates a significant treatment‐by‐subgroup interaction with regard to the estimated treatment differences for that trial (two‐sided significance test)

FIGURE 2

Change from baseline in A, glycated haemoglobin (HbA1c), and B, body weight, by duration of diabetes. Abbreviations: flex, flexibly dosed; OAD, oral antidiabetes drug; SGLT2i, sodium‐glucose cotransporter‐2 inhibitor; SU, sulphonylurea. †Including metformin, an SU, an SGLT2i or a thiazolidinedione. Analyses were conducted at the end of treatment on data from the full analysis set using the trial product estimand. No significant treatment‐by‐subgroup interactions were observed with regard to the estimated treatment differences for each trial (two‐sided significance test)

FIGURE 3

Change from baseline in A, glycated haemoglobin (HbA1c), and B, body weight, by baseline HbA1c. Abbreviations: flex, flexibly dosed; OAD, oral antidiabetes drug; SGLT2i, sodium‐glucose cotransporter‐2 inhibitor; SU, sulphonylurea. †Including metformin, an SU, an SGLT2i or a thiazolidinedione. Analyses were conducted at the end of treatment on data from the full analysis set using the trial product estimand. The P value indicates a significant treatment‐by‐subgroup interaction with regard to the estimated treatment differences for that trial (two‐sided significance test)