We have previously reported that supaglutide displayed distinguished PK profile and prolonged in vivo half-life (Wang et al., 2010). In the present study, we demonstrated that in established obese mouse model induced by HFD feeding; twice a week injection of supaglutide elicited a moderate but significant reduction of body weight by ~5%. The body weight sparing effects was consistently observed in db/db mice. It was noted that supaglutide at the tested doses showed dose-dependent effects in lowering blood glucose; however, this dose-response relationship was not found in its weight sparing effects in db/db mice, implying different mechanisms underlying the glucose-lowering and weight-reduction effects of supaglutide in db/db mice. Previous clinical studies demonstrated that a modest weight loss provides beneficial effects on cardiovascular risk factors in obese patients (Goldstein, 1992; Van Gaal et al., 1997). The outcome of present study that Supaglutide reduces body weight in obese mice implies a clinical relevance in the terms of metabolic disorders and cardiac beneficial effects.