Here, we investigated whether supaglutide exerts regulatory effects on energy metabolism using murine obese model induced by high fat diet (HFD) feeding. We showed that twice a week injection of supaglutide exerted body weight-sparing effects and improved glucose tolerance and insulin sensitivity in HFD-induced obese mice. Moreover, supaglutide-treated mice were more tolerant to cold exposure and demonstrated upregulated thermogenic uncoupling protein 1(Ucp1) expression in the inguinal white fat. Our results imply that supaglutide may serve as an alternative potent GLP-1 therapy for obesity, type 2 diabetes, and other metabolic diseases.