The rapidly increasing prevalence of obesity and obesity-associated morbidity is causing an ever-increasing global burden. Beyond lifestyle modifications, pharmacological approaches to losing body weight to achieve a decrease in cardiometabolic complications are in the spotlight. Pre-existing anti-obesity medications (AOMs) approved for long-term prescription use showed a weight reduction of around 5% more than placebo. In contrast to the modest efficacy of pre-existing AOMs, two newly developed, weekly-administered injectable drugs, semaglutide and tirzepatide, exhibited outstanding weight-loss effects in a series of multinational randomized phase III trials. Considering that these two peptides are the most promising candidates for the upcoming battle in the anti-obesity market, comparison of their efficacy and safety is essential. This review summarizes the body weight reduction efficacy, glycemic control, and safety of semaglutide up to a 2.4-mg dose and tirzepatide up to a 15-mg dose, focusing on the Semaglutide Treatment Effect in People with Obesity (STEP) 2, SURPASS-1, and SURPASS-2 trials, the subjects of which were all patients with type 2 diabetes mellitus.