Effects Of Glucagon-like Peptide-1 Receptor Agonist On Early Diabetic Nephropathy

Background and objective: Diabetic nephropathy is a chronic kidney disease which caused by diabetes.Diabetic nephropathy is one of the most serious complications of diabetes that has affected about more than thirty percent of the patients with diabetes.Its incidence increased year by year,it is also the most common cause of end-stage kidney failure,which brought great social and economic burden to the patients.In recent years,glucagon-like peptide-1(GLP-1) receptor agonist has been the hotspot of diabetes treatment.Besides benefit on blood sugar control, GLP-1 also plays an unique role in kidney.The main objective of this study is to explore the effect on renal function in patients with early diabetic nephropathy of the GLP-1 receptor agonists,especially its influence on reducing the microalbuminuria and delaying the decline in glomerular filtration rate(GFR), in order to prevent the occurrence of the disease more effectively,delay its progress and improve its prognosis.Methods:Select the diabetic nephropathy patients hospitalized or outpatiented from September 1st 2013 to March 1st 2015, with 24h-microalbuminuria(UMA)between 30 mg and 300 mg, GFR more than 60ml/min/1.73m2,blood glucose control is poor by applicating premixed insulin or oral hypoglycemic drugs,systolic blood pressure(SBP) under 140 mm Hg without using angiotensin-converting enzyme inhibitor and angiotensin II receptor blockers.The total number selected was 91 cases(male 56, female35),randomly divided into two groups-the GLP-1 group and insulin intensive group. The GLP-1 group,inject exenatide 5μg or 10μg twice a day,an hour before breakfast and dinner,adjust the original antidiabetic drug and exenatide dose according to blood glucose, the maximum dose of exenatide is 20μg/d.Intensive insulin group, exchange Insulin aspart and Glargine Insulin equivalent of the premixed insulin dosage,adjust the original oral drug and insulin dosage according to blood sugar gradually.Guidance of diet and exercise, exenatide and insulin injection, blood glucose monitoring method are from the professional staff. Follow-up the outpatient to the end of the study,using self control and the group control.In the GLP-1 group,before treatment and 4 weeks,12 weeks and 24 weeks after treatment, fasting blood glucose(FBG),2-hour postprandial blood glucose(2h PBG),weight,SBP, renal function, microalbuminuria(MA)were measured, before and 24 weeks after treatment,glycosylated hemoglobin(Hb Alc) was measured,GFR,UMA and body mass index(BMI) were calculated.Intensive insulin treatment group:FBG,2h PBG, Hb Alc, MA, renal function were measured and GFR and UMA were calculated before and 24 weeks after treatment. The obtained data were statistically analyzed.Results: Finally,there are 46 patients completed the study in GLP-1 group,28 male cases, 18 female cases.There are 43 patients completed 24 weeks of intensive insulin therapy in Insulin intensive group, 26 male cases, 17 female cases. The age, duration of disease, BMI, SBP, premixed insulin dosage, Cpeptide, Hb Alc, FBG,GFR and UMA in two groups have no significant difference, P > 0.05, datas of two groups are comparable.Compared with those before the treatment,FBG, 2h PBG, Hb A1 c, UMA decreased significantly after24 weeks’ treatment in two groups of patients, P<0.05, with statistical significance,while the GFR has no statistically significant difference(P>0.05).After treatment for 24 weeks, FBG, 2h PBG, Hb Alc, GFR of the two groups are compared,and have no significant statistically difference(P>0.05);UMA were both significantly decreased,the decrease of the GLP-1 group was more obvious,(p=0.016).After the treatment with exenatide,cystatin C decrease significantly,the GFR and creatinine have no statistically significant differences(P>0.05),the body weight, SBP, and blood lipid were lower than before, the difference was statistically significant(P<0.05).The major adverse reactions during the administration of the exenatide were gastrointestinal reactions, mostly due to prolonged treatment time and tolerance, no serious adverse reactions occurred.Conclusion: In patients with early diabetic nephropathy, glucagon-like peptide-1 agonists can effectively reduce the patients’ microalbuminuria, delay the decline speed of the glomerular filtration,improve renal function, delay the development of diabetic nephropathy.