AIM: To investigate the effect of genetic variation of calmodulin 45 T/G (APM1-45) gene polymorphism on the clinical efficacy and T2DM patients with type 2 diabetes mellitus treated with liralutide. METHODS: A total of 95 patients with type 2 diabetes admitted to the third people's Hospital of Haikou City from August 2016 to October 2019 were selected as subjects of study. All patients were treated with liraglutide for 14 weeks. And the changes of blood glucose level, BMI index and relative mRNA expression were recorded before and after treatment. Besides record the occurrence of adverse reactions. RESULTS: The distribution frequency of APM1-45 (rs2241766) in the study population was 46 cases of TT type (48.42%), 43 cases of TG type (45.26%), 6 cases of GG type (6.32%). After treatment, the 2h PG, HbAIc, FPG and BMI related indexes of each group decreased significantly compared with those before treatment, and there was statistical difference (P<0.05); the FPG, HbA1c and BMI indexes of TT genotype patients decreased more compared with TG/GG genotype patients, but there was no statistical difference between them (P>0.05). The relative expression of mRNA in TT genotype was significantly lower than that in TG/GG genotype (P<0.05). The overall adverse reactions of patients were less, there was no statistical difference between the groups. CONCLUSION: For type 2 diabetic patients, the treatment of liraglutide alone has obvious effect, and the incidence of adverse reactions is low. There is a certain correlation between G allele and T2DM susceptibility, while T allele carrier has a better effect on the treatment of liraglutide.