We developed a GLP-1 analog supaglutide by fusing a pair of GLP-1 molecules with immunoglobulin constant region that contains partial hinge chains (Kumar et al., 2007; Wang et al., 2010). While the fusion chimera displayed high avidity to the GLP-1 receptor, pharmacokinetic studies showed that a single intraperitoneal injection of supaglutide led to rapid increase in drug concentration in circulation and maintaining at high levels for more than 1 week (Wang et al., 2010). The long lasting effects of supaglutide were probably due to its large molecular mass (~60 kD) which made it not easily cleared by kidney (Wang et al., 2010). Moreover, the fusion protein appeared relatively resistant to DPPIV degradation (Wang et al., 2010) and possibly other degrading enzymes (Hupe-Sodmann et al., 1995), as exemplified by both in vitro and in vivo studies (Wang et al., 2010). Notably, supaglutide has biological relevance since it showed high binding affinity to GLP-1 receptor and stimulated insulin secretion in a glucose-dose dependent manner in insulin-secreting INS-1 cells (Wang et al., 2010). Supaglutide has long-lasting effects on the modulation of glucose homeostasis, exemplified by the observations that the mice displayed significantly reduced glucose excursion as determined by intraperitoneal glucose tolerance test (IPGTT) performed 1 week after a single injection (Wang et al., 2010). Importantly, supaglutide and its relevant constructs are found to be effective in reducing the incidence of diabetes in multiple-low-dose streptozotocin (STZ)-induced type 1 diabetes and db/db type 2 diabetes in mice (Kumar et al., 2007; Soltani et al., 2007; Wang et al., 2010). One mechanism underlying the protective role of GLP-1 in diabetes is its insulinotrophic and beta cell protective actions which comply with GLP-1 therapeutic effects in the treatment of diabetes. However, limited data is available in term of this GLP-1 analog on energy homeostasis.