Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trial

Once-Weekly Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Common OAD: a Subgroup Analysis from SUSTAIN 2–4 and 10

“…A significantly greater reduction in total cholesterol was observed in SUSTAIN 3 with semaglutide than with exenatide ER in the background MET ? SU subgroup but not in the background MET subgroup, driven both by a greater reduction with semaglutide 1.0 mg and a lower reduction with Table 4 Adverse events leading to premature treatment discontinuation in the safety analysis set The proportion of subjects who prematurely discontinued treatment because of adverse events was mostly consistent between background OAD subgroups, but the proportion was generally higher with semaglutide than with comparators, as observed across the SUSTAIN programme [8][9][10][11][12][13][14][15][16][17]. Across the four SUSTAIN trials analysed here, the event rate for severe or BG-confirmed symptomatic hypoglycaemia and minor hypoglycaemia reported with semaglutide was either comparable to or lower than the rate with active comparators (liraglutide, exenatide ER, sitagliptin or insulin glargine).…”

“…Semaglutide is a GLP-1 analogue, with 94% amino acid homology to native GLP-1. The efficacy and safety of once-weekly subcutaneous (s.c.) administration of semaglutide has been established in the global phase 3 clinical trial programme SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes), which has included a broad range of subjects with T2D with or without background OADs or insulin [8][9][10][11][12][13][14][15][16][17].…”

“…The number and type of background OAD therapies in subjects varied across the SUSTAIN trials and included MET (which is considered the backbone of T2D treatment and recommended as first-line therapy by most treatment guidelines) as a monotherapy or in combination with SU, one of the most common second-line therapies [3][4][5]7]. Subjects in the SUSTAIN trials remained on stable therapy, including prior background treatment, unless rescue criteria were met [8][9][10][11][12][13][14][15][16][17].…”

Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised controlled clinical trial

“…Both semaglutide and canagliflozin are associated with substantial reductions in body weight. Across the SUSTAIN 1-10 trials, semaglutide has demonstrated significantly greater weight loss vs all comparators, with absolute change in body weight ranging from −3.8 to −6.5 kg with semaglutide 1.0 mg [11][12][13][14][15][16][17][18][19][20]. Canagliflozin has consistently demonstrated weight reductions of 2.5 to 4.7 kg in clinical trials [24].…”

“…Semaglutide is a GLP-1RA approved for the subcutaneous, once-weekly treatment of type 2 diabetes [9,10]. The efficacy and safety of once-weekly semaglutide have been established in the SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) clinical trial programme across the continuum of care in individuals with type 2 diabetes vs placebo and a range of comparators (SUSTAIN 1-5 and 7-10) [11][12][13][14][15][16][17][18][19] and in a cardiovascular outcomes trial (SUSTAIN 6) [20]. Canagliflozin is an SGLT-2i approved for the oral, once-daily treatment of type 2 diabetes [21].…”