Five-week chronic treatment in db/db mice with combination therapy and a single-molecule dual agonist of GPR40 and GPR120 resulted in metabolic benefits better than monotherapy. A: Body weight changes. B: Nonfasting blood glucose changes. C: Fasting blood glucose levels on study day 35. D: Fasting plasma insulin levels on study day 35. E: oGTT performed on study day 28. F: Glucose AUC (0–120 min) during oGTT. G: Nonfasting plasma TG on study day 35. H: Fasting plasma TG on study day 35. Data are mean ± SEM. Combo, MK-2305 at 10 mpk and Cpd A at 30 mpk were codosed (n = 8); Dual, GPR40/GPR120 dual agonist Cpd C dosed at 30 mpk (n = 8). db/+: age-matched genetic control (n = 8); GPR40, GPR40 selective agonist MK-2305 dosed at 10 mpk (n = 8); GPR120, GPR120 selective agonist Cpd A dosed at 30 mpk (n = 8); Rosi, Rosi dosed at 3 mpk (n = 8); vehicle, regular diet D5053 (n = 8). . One-way ANOVA test was applied to db/db mice with treatment (the db/+ group was excluded from statistical analysis). * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001.