SUSTAIN 8: Semaglutide outperforms canagliflozin as second-line therapy for type 2 diabetes
medwireNews: Treatment with the glucagon-like peptide (GLP)-1 receptor agonist semaglutide results in better glycemic control than the sodium-glucose cotransporter (SGLT)2 inhibitor canagliflozin among people with type 2 diabetes uncontrolled on metformin, indicate the SUSTAIN 8 trial results.
The phase 3b study – presented at the 55th EASD Annual Meeting in Barcelona, Spain, and published simultaneously in The Lancet Diabetes & Endocrinology – included 788 participants aged an average of 56.6 years who were randomly assigned to receive subcutaneous semaglutide 1 mg once weekly or oral canagliflozin 300 mg once daily for a total of 1 year.
Presenting author Ildiko Lingvay (UT Southwestern Medical Center, Dallas, Texas, USA) told the audience that the 394 patients treated with semaglutide experienced a significantly greater decrease in glycated hemoglobin (HbA1c) levels from baseline to the 1-year follow-up than the 394 people given canagliflozin, with average decreases of 1.5% versus 1.0% from baseline values of 8.3% and 8.2%, respectively.
Moreover, participants in the semaglutide arm were significantly more likely than those in the canagliflozin group to achieve the American Diabetes Association’s HbA1c target of less than 7.0% (66.1 vs 45.1%), as well as the American Association of Clinical Endocrinologists’ target of 6.5% or lower (52.8 vs 23.6%).
Treatment with semaglutide versus canagliflozin also resulted in a significantly greater reduction in bodyweight (5.3 vs 4.2 kg), and a significantly greater proportion of participants treated with the GLP-1 receptor agonist achieved at least 10% loss in bodyweight over the study period (22 vs 9% for the canagliflozin group).
Lingvay said that 76% of patients in the semaglutide group and 72% of those given canagliflozin experienced adverse events (AEs), and the corresponding rates of gastrointestinal AEs were 47% and 28%. In all, 9.7% and 5.1% of patients in the semaglutide and canagliflozin groups, respectively, discontinued treatment due to adverse events.
“SUSTAIN 8 provides clinically relevant information regarding the head-to-head comparison of a GLP-1 [receptor agonist] and [an SGLT2 inhibitor] as second-line therapy in patients with [type 2 diabetes],” he concluded.
Despite semaglutide providing better glycemic outcomes than canagliflozin, a substudy of 178 SUSTAIN 8 participants found no significant differences in body composition changes among patients treated with the two drugs.
Rory McCrimmon (University of Dundee, UK), who presented these findings, reported that both semaglutide and canagliflozin resulted in “substantial positive changes in body composition,” including reductions in total fat mass (3.4 and 2.6 kg loss, respectively) and waist circumference (3.9 and 2.5 cm reduction, respectively).
He said that these results support the role of both drugs “as relevant treatment options for type 2 diabetes.”
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