The efficacy of dulaglutide in the treatment of kidney, dulaglutide can slow down the process of renal function
Author:固拓多肽合成公司    Published in:2020年07月08日
Abstract:The efficacy of dulaglutide in the treatment of kidney, dulaglutide can slow down the process of renal function

The 2017 scientific research shows that the treatment of dulaglutide once a week can reasonably manipulate the blood glucose level of diabetic patients with moderate to severe nephropathy, and can slow down the progression of kidney disease.


Review of scientific research


Diabetic nephropathy is a common disease in diabetic patients (about 40%), and it is also the main cause of chronic kidney disease in the world. Because most of the hypoglycemic drugs contain insulin and are mainly cleared by renal function, the dosage should be adjusted or forbidden to be used in patients with nephropathy, which results in the limitation of hypoglycemic therapy for patients with moderate to severe chronic kidney disease. On the other hand, the decrease of drug clearance in patients with nephropathy can lead to an increase in the risk of low blood glucose. Therefore, it is of great practical significance to find safe hypoglycemic drugs for patients with nephropathy.


Dulaglutide, a potent glucagon like peptide 1 (GLP1) receptor inhibitor, was approved for treatment of type 2 diabetes in 2017. Without renal function clearance, it is not easy to increase drug exposure in patients with nephropathy. However, there are few clinical trials on GLP ­ 1 receptor inhibitors in patients with moderate to severe nephropathy at this stage, and most of them are placebo-controlled trials. To establish the effectiveness and safety factor of dulaglutide in diabetic patients with moderate to severe nephropathy, Katherine ruttle, a scientific research team from the University of Washington, conducted a multi center, open label, randomized controlled trial. The results of the study were published in the lancet Diabetes & Endocrinology journal.


Reference map of dulaglutide


A total of 577 subjects were included in the scientific research. The inclusion criteria were: adult patients with type 2 diabetes mellitus, moderate to severe chronic kidney disease (stage 3-4), HbA1c of 7.5-10.5%. They were treated with insulin or insulin plus oral hypoglycemic drugs, and took large doses of angiotensin-2-converting enzyme inhibitors or angiotensin-2 receptor antagonists. The subjects were randomly given dulaglutide 1.5mg, once a week (n = 193), dulaglutide 0.75mg, once a week (n = 190) and insulin glargine once a day (n = 194) for 52 weeks according to the proportion of 1:1:1. The main endpoint was HbA1c at 26 weeks, and the non inferiority margin was 0.4%. The primary and secondary endpoints were estimated renal tubular filtration rate (EGFR) and urinary albumin creatinine ratio (UACR).


Main findings


At the 26th week of treatment, HbA1c of the three groups decreased compared with the baseline. The least square mean (LSM) of dulaglutide 1.5mg group was - 1.2%, 0.75mg group was - 1.1%, insulin glargine group was - 1.1%, P ≤ 0.0001. The HbA1c transition in dulaglutide 1.5mg and 0.75mg groups was not less than that of insulin glargine. After 52 weeks of treatment, dulaglutide was still reasonable.


During the treatment period, the patients in the dulaglutide group lost weight, while those in the insulin glargine group gained weight. There was no significant difference in the incidence of severe adverse reactions between dulaglutide 1.5 mg, 0.75 mg and insulin glargine (20% vs 24% vs 27%). The incidence of nausea and vomiting (20% vs 14% vs 5%) and diarrhea (17% vs 16% vs 7%) was higher in the dulaglutide group, while the incidence of symptomatic hypoglycemia was lower, 4.4/person-year in a group with 1.5mg, 4.3/person-year in a group with 0.75mg, and 9.6/person-year in a group with insulin glargine. In addition, EGFR of patients in dulaglutide group was higher than that in control group, and the decrease of UACR was not statistically significant.


The efficacy of dulaglutide in the treatment of kidney, dulaglutide can slow down the process of renal function

Changes of EGFR


The study showed that in patients with type 2 diabetes mellitus complicated with moderate to severe chronic kidney disease, the hypoglycemic effect of dulaglutide once a week was similar to that of insulin glargine, while EGFR was reduced less. Dulaglutide may be safe for blood glucose control in patients with moderate to severe chronic kidney disease.


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