Abstract 171
Authors: Shabeer D , Knop Filip K. , Cariou Bertrand , Eliasson Johanna , Frappin Guillaume , Kaltoft Margit S. , Montanya Eduard , Rosenstock Julio 
Published: February 2023

Background and Objective: Maintaining adequate glycaemic control reduces the long-term risk of some type 2 diabetes (T2D) complications. Despite this, many individuals with T2D do not have their treatment intensified and remain on suboptimal HbA1c targets. It is therefore important to consider which treatment will enable patients to maintain glycaemic control over time. To date, continuous patient-level data for duration of time spent with HbA1c < 7.0% (53 mmol/mol) and the likelihood of maintaining HbA1c < 7.0% in the PIONEER efficacy trials have not been reported. The PIONEER phase 3a clinical trial programme evaluated the efficacy and safety of oral semaglutide vs active comparators (empagliflozin, sitagliptin and subcutaneous [s.c.] liraglutide) and placebo in patients with T2D. – PIONEER 2–4 and 7 consistently demonstrated that greater proportions of patients achieved HbA1c < 7.0% at week 26 (or week 52 for PIONEER 7) with oral semaglutide compared with active comparators or placebo.

Objective: This post hoc analysis of the PIONEER 2–4 and 7 trials aimed to determine the duration of time patients spent with HbA1c.

Methods: Mean duration of time spent with HbA1c <7.0%. Proportion of patients achieving HbA1 <7.0% for different time intervals. Estimated odds ratio of achieving HbA1c <7.0% at week 26 (week 24 for PIONEER 7, as week 26 data were unavailable) and week 52 (and week 78 for PIONEER 3). Data are for all randomised patients from PIONEER 2–4 and 7 assigned to receive oral semaglutide or active comparator (empagliflozin, sitagliptin, s.c. liraglutide). Oral semaglutide dose was escalated, starting at 3 mg once daily and increasing to 7 mg after 4 weeks and then to 14 mg after 8 weeks in all trials except PIONEER 7, which used a flexible dose adjustment approach based on HbA1c and gastrointestinal tolerability. Empagliflozin was initiated at 10 mg and escalated to 25 mg after 8 weeks. Sitagliptin was initiated at 100 mg and not escalated. S.c. liraglutide was initiated at 0.6 mg and escalated to 1.2 mg and then 1.8 mg after 1 and 2 weeks, respectively. For each patient, duration of time spent with HbA1c <7.0% was calculated based on the HbA1c–time curve derived using all visits with HbA1c measurements and linear interpolation between two consecutive visits. Study visits were scheduled for every 4–8 weeks. Outcomes were evaluated for oral semaglutide vs active comparators using the on-treatment without rescue medication observation period. Patients who discontinued treatment early or who used rescue medication were considered not in glycaemic control after the event in question.

Results: Mean baseline HbA1c ranged from 8.0 to 8.3% (64–67 mmol/mol). Across PIONEER 2, 3 and 7, mean duration of time spent with HbA1c <7.0% was greater with oral semaglutide 14 mg, or flexibly dosed, than with oral competitors empagliflozin 25 mg and sitagliptin 100 mg (Figure 2). – Similar mean duration was observed between oral semaglutide and s.c. liraglutide 1.8 mg in PIONEER 4. There was a significantly greater likelihood of maintaining HbA1c <7.0% for >75% of the trial duration compared with empagliflozin 25 mg and sitagliptin 100 mg (Figure 3). – Similar proportions were observed between oral semaglutide 14 mg and s.c. liraglutide 1.8 mg

Summary: Oral semaglutide 14 mg, or flexibly dosed, resulted in a greater duration of time spent with HbA1c <7.0% vs empagliflozin and sitagliptin. Oral semaglutide 14 mg resulted in a similar duration of time spent with HbA1c < 7.0% to s.c. liraglutide, despite a longer dose escalation with oral semaglutide. The odds of maintaining HbA1c <7.0% at weeks 24/26 and 52 (and 78 for PIONEER 3) were significantly greater with oral semaglutide vs empagliflozin, sitagliptin and s.c. liraglutide.

Conclusion: In patients with T2D, oral semaglutide may lead to longer sustained glycaemic control vs oral comparators, on an individual level