Kanters S, et al. - Among subjects with type 2 diabetes (T2D) inadequately controlled with 1–2 oral antidiabetics (OADs), researchers assessed the comparative effectiveness of once-weekly semaglutide in relation to sodium-glucose cotransporter 2 inhibitors (SGLT-2is) licensed in Europe and North America via a systematic literature review and network meta-analysis (NMA). Forty-eight publications with 21 trials were involved. The mean differences (MD) in change from baseline in HbA1c of once-weekly semaglutide 1.0 mg vs SGLT-2is ranged from −0.56% to −0.95% for canagliflozin 300 mg, and dapagliflozin 5 mg, respectively. The MD in change from baseline in weight of once-weekly semaglutide 1.0 mg vs SGLT-2is ranged from −1.35 kg for canagliflozin 300 mg to −2.48 kg and for dapagliflozin 5 mg, while a change from baseline in fasting plasma glucose ranged from −0.41 mmol/L to −1.37 mmol/L for canagliflozin 300 mg and for dapagliflozin 5 mg, respectively. In decreasing systolic blood pressure, once-weekly semaglutide was not statistically distinguishable from any SGLT-2is. Statistically significant and clinically important decreases in HbA1c and body weight were exhibited with once-weekly semaglutide in T2D subjects not well controlled with 1–2 OADs vs all SGLT-2is licensed in Europe and North America.