Study On The Influencing Factors Of Gastrointestinal Adverse Reactions Induced By Glucagon-like Peptide-1 Receptor Agonists

Background:Glucagon-like peptide-1 receptor agonists are new types of treatment for type 2 diabetes,especially for obese patients.They are rapidly and widely used in clinical practice because these drugs can significantly reduce the body weight of obese patients and are not easy to cause hypoglycemic reactions.However,in the clinical treatment process,these drugs may cause different degrees of gastrointestinal reactions,such as nausea,vomiting,diarrhea,bloating and etc.Even some patients can't tolerate and stop using these drugs,which seriously affects the patient's compliance with the drugs.How to avoid or reduce the occurrence of adverse reactions more effectively has become an urgent problem to be solved.This article will analyze the relationship between genetic and non-genetic factors and gastrointestinal adverse reactions caused by GLP-1 receptor agonists,in order to obtain independent influencing factors of gastrointestinal adverse reactions,providing a preliminary reference for clinical individualized drugs.Objectives:The main purposes of this research are to analyze the characteristics of gastrointestinal adverse reactions caused by glucagon-like peptide-1 receptor agonists in Chinese Han type 2 diabetic patients.And to explore the influencing factors related to the occurrence of gastrointestinal adverse reactions,in order to provide a theoretical reference for the safety and effective application of glucagon-like peptide-1 receptor agonists.Methods:This study included the patients who were in the Department of Endocrinology of Qianfoshan Hospital from January 2017 to December 2018,with the diagnosis of type 2 diabetes and with glucagon-like peptide-1 receptor agonists.Collect and sort out various medical documents such as the course record of the research object,the patient's medical order,and the test list.Record the basic information(name,gender,age,height,weight,body mass index),medication status(dosage type,combined medication),laboratory test indicators(liver function index,renal function index,blood lipid level)and gastrointestinal adverse reactions in detail.First we analyzed univariate factors of the non-genetic factors and genetic factors of gastrointestinal adverse reactions induced by GLP-1 receptor agonists.And then,suspicious factors were included in multivariate logistic regression to explore independent risk factors related to gastrointestinal adverse reactions.Results:?Sixty-three of the 137 patients with type 2 diabetes who received the glucagon-like peptide-1 receptor agonists in this study experienced varying degrees of gastrointestinal adverse effects.The overall incidence of gastrointestinal adverse reactions was 46.0%,of which the incidence of mild gastrointestinal adverse reactions was 29.9%,and the incidence of moderate gastrointestinal adverse reactions was 16.1%.Among the 63 patients with gastrointestinal adverse reactions,the incidence of gastrointestinal adverse reactions was 28.5%in men and 17.5%in women.The incidence of gastrointestinal adverse reactions caused by exenatide was 21.9%,and liraglutide was 24.1%.?The results of non-genetic factors analysis showed that the body weight and body mass index of the without gastrointestinal adverse reaction group were significantly higher than those of the adverse reaction group,and the worse the adverse reactions,the smaller the body weight and body mass index is.The probability of developing moderate gastrointestinal adverse effects with exenatide was significantly higher than that of liraglutide(P = 0.008).All patients with moderate gastrointestinal side effects caused by liraglutide were combined with metformin.There was no significant association between gastrointestinal adverse effects and AST,ALT,Cr,HDL-C,LDL-C,TC,and TG.?The results of genetic analysis showed that the genetic polymorphisms of rs10305420 and rs3765467 of type 2 diabetes and healthy volunteers were consistent with the Hardy-Weinberg equilibrium law(?2 =2.58,P=0.11(rs10305420);?2 = 0.13,P =0.72(rs3765467)).The occurrence of gastrointestinal adverse reactions caused by GLP-1 receptor agonists was not significantly associated with the polymorphisms of the GLP-1R gene rs10305420 and rs3765467.The HDL-C level of the rs10305420 T allele carrier was significantly lower than that of the CC genotype(1.00±0.18 vs.1.09±0.22,P=0.02).The triglyceride(TG)level of the rs3765467 A allele carrier was higher than that of the GG type(2.75±2.19 vs.2.07±1.36,P=0.03).There was no significant association between GLP-1R gene polymorphisms and metabolic indicators such as BMI,TC,TG,HDL-C,LDL-C,FBG and HbAlc in healthy volunteers.?Logistic multivariate linear regression analysis showed that small BMI was an independent risk factor for gastrointestinal adverse reactions in GLP-1 receptor agonists.Conclusions:Exenatide is more susceptible to moderate gastrointestinal side effects than liraglutide.The genetic polymorphisms of GLP-1R gene rs10305420 and rs3765467 were not associated with the occurrence of gastrointestinal adverse reactions,but were significantly associated with blood lipid levels.BMI is an independent risk factor for gastrointestinal adverse reactions in GLP-1 receptor agonists.The smaller the body mass index,the more likely gastrointestinal adverse reactions occur.