The Effect Of Dulapeptide Combined With Englergin On Urinary Protein In Patients With Early Diabetic Nephropathy

Objective:The objective of this study was to observe whether the combination therapy of empagliflozin,an SGLT-2 inhibitor(Sodium glucose cotransporter2 inhibitor),and dulaglutide,a GLP-1 receptor agonist(Glucagon-like peptide 1 receptor agonist),in the treatment of early-stage type 2 diabetic nephropathy could achieve a synergistic effect compared to the use of empagliflozin alone.The aim was to further reduce urinary protein excretion and delay the progression of kidney disease,providing new treatment options and improved strategies for urinary protein management in patients with diabetic nephropathy.Methods:A total of 150 patients with poorly controlled blood glucose and early-stage type 2 diabetic nephropathy were divided into a control group and an experimental group.The control group received empagliflozin 10mg/day(trade name: Onglyza,manufacturer: Astra Zeneca,China Food and Drug Administration registration number HJ20170351)orally in addition to their original hypoglycemic treatment regimen.The experimental group received empagliflozin 10mg/day orally in addition to their original hypoglycemic treatment regimen,combined with dulaglutide 1.5mg/week(trade name: Trulicity,manufacturer: Eli Lilly and Company,China Food and Drug Administration registration number S20190022)subcutaneous injections.Insulin glargine(trade name: Lantus,manufacturer: Sanofi,China Food and Drug Administration registration number J20140052)subcutaneous injections were added for Both groups if blood glucose control was inadequate.The treatment duration for both groups was 6 months,with follow-up visits at baseline,3 months,and 6 months.The measured parameters included the following: demographic data,ACR(urine albumin-to-creatinine ratio),24-hour urine protein(24h UP),blood pressure,lipid profile,body weight,body mass index(BMI),glycated hemoglobin(HbA1c),fasting blood glucose(FBG),postprandial blood glucose(2hPG),uric acid(UA),estimated glomerular filtration rate(eGFR),and changes in interleukin-6(IL-6),an inflammatory marker associated with diabetic nephropathy.The impact of the two treatment regimens on urinary protein excretion and the differences in glycemic control,lipid profile,blood pressure,and adverse reactions between the two groups were observed and recorded.The primary outcome measure was the ACR level at the 6-month follow-up.Results:1.General baseline characteristics(gender ratio,age,duration of illness)and observed parameters including ACR,24 h UP,HbA1c,FBG,2hPG,UA,eGFR,blood pressure,lipid profile,body weight,BMI,and IL-6 showed no significant statistical differences between the two groups(P>0.05).2.Urinary protein indicators: After treatment,ACR significantly decreased in both groups compared to baseline,showing a statistically significant difference(P<0.05).Furthermore,the experimental group showed a more significant decrease in ACR compared to the control group(P<0.05),and this effect is time-dependent(P <0.05).Similarly,24 h up significantly decrease in both groups,showing a statistically significant difference(P<0.05),with a more profound decrease in the experimental group compared to the control group(P<0.05).3.Blood glucose indicators: After treatment,FBG,HbA1c,and 2hPG significantly decreased in both groups compared to baseline,showing a statistically significant difference(P<0.05).Additionally,the experimental group showed a more significant decrease in 2hPG and HbA1c compared to the control group,with a statistically significant difference(P<0.05).However,there was no significant statistical difference in FBG between the two groups after treatment(P>0.05).4.Kidney-related indicators: After treatment,eGFR showed no significant statistical difference compared to baseline in both groups(P>0.05).UA significantly decreased in both groups after treatment,showing a statistically significant difference(P<0.05).However,there was no significant statistical difference in UA between the two groups after treatment(P>0.05).5.Inflammation indicators: After treatment,IL-6 significantly decreased in both groups compared to baseline,showing a statistically significant difference(P<0.05).Moreover,the experimental group exhibited a more significant decrease in IL-6 compared to the control group(P <0.05),and this effect had an interaction with time(P<0.05).6.Lipid-related indicators: After treatment,TC and TG significantly decreased in both groups compared to baseline,showing a statistically significant difference(P<0.05).Additionally,the experimental group demonstrated a more significant decrease in TC and TG compared to the control group,with a statistically significant difference(P<0.05).LDL-C also showed a significant decrease compared to baseline and the concurrent control group(P<0.05).However,there was no significant statistical difference in HDL-C between the two groups after treatment(P>0.05).7.Blood pressure,body weight,and BMI: After treatment,SBP,body weight,and BMI significantly decreased in both groups compared to baseline,showing a statistically significant difference(P<0.05).Furthermore,the experimental group exhibited a more significant decrease in SBP,body weight,and BMI compared to the control group(P<0.05).However,there was no significant statistical difference in DBP between the two groups after treatment(P>0.05).Conclusion:In early-stage diabetic nephropathy patients,combination therapy with empagliflozin and dulaglutide provides a greater reduction in urinary protein excretion and slows down the progression of diabetic nephropathy compared to empagliflozin monotherapy.This effect is time-dependent,with a more pronounced reduction in urinary protein observed as the duration of combination therapy increases.Additionally,this combination therapy facilitates safer and faster achievement of blood glucose targets while effectively promoting weight loss,blood pressure control,lipid modulation,and reducing inflammation.