Extended Data Fig. 6: Drug effects in db/db mice and in lean WT and Vglut2-GLP-1R KO mice.
From: GLP-1R–GIPR–PPARα/γ/δ quintuple agonism corrects obesity and diabetes in mice
a–h, Leptin receptor deficient (db/db) mice were treated once-daily via s.c. injections of GLP-1:GIP + Lani (n = 9), GLP-1:GIP:Lani (n = 8) or vehicle (n = 9) for 20 days. 10 nmol kg−1. a, Body weight. b, Change in fat and lean mass. c, Cumulative food intake. d, Fasting blood glucose. e, Glucose tolerance test. f, Insulin tolerance test. g, Baseline-corrected insulin tolerance test. h, Homeostatic model assessment of insulin resistance (HOMA-IR). i, Conditioned Taste Avoidance (CTA) in lean wildtype and Vglut2-GLP-1R KO mice 24 h after single s.c. administration of GLP-1:GIP (WT, n = 20; KO, n = 9), GLP-1:GIP:Lani (WT, n = 21; KO, n = 9) or vehicle (WT, n = 20; KO, n = 9). 10 nmol kg−1. j–p, Lean wildtype mice were treated once-daily via s.c. injections of GLP-1:GIP + Lani, GLP-1:GIP:Lani or vehicle for 14 days. 10 nmol kg−1. j, Body weight (n = 8 each group). k, Change in fat and lean mass (Vhcl, n = 8; GLP-1:GIP:Lani, n = 8; GLP-1:GIP + Lani, n = 6). l, Cumulative food intake (n = 8 each group). m, Fasting blood glucose (n = 8 each group), n, Fasting plasma insulin (Vhcl, n = 8; GLP-1:GIP:Lani, n = 8; GLP-1:GIP + Lani, n = 7). o, Plasma triglycerides (n = 8 each group). p, Plasma cholesterol (n = 8 each group). Data were analysed using one-way ANOVA with Bonferroni post hoc multiple-comparison test (b,d,h,k,m,o,p), two-way repeated-measures ANOVA (a,c,e–g,j,l) or Kruskall-Wallis test with uncorrected Dunns’s test (i,n). Data are mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001. Exact P-values, n-values and detailed statistics are provided in Supplementary Tables 1 and 3 and the Data Source File.
