Saxagliptin Improves Urinary Albumin/Creatinine Ratio In Patients With Type 2 Diabetes Mellitus By Targeting The NLrp3/ASC Inflammasome

Objective :The aim of the present study was to determine the effect of saxagliptin on urinary albuminuria/creatinine ratio in patients with type 2 diabetes mellitus by targeting the NLrp3/ASC inflammasome.Methods :A total of 115 patients with type 2 diabetes mellitus(age>18 years,<84 years,hemoglobin A1c(HbA1c)<8.0%),0mg/gCr<urinary albuminuria/creatinine ratio <1000mg/gCr,were randomized to patients taking saxagliptin 5 mg or other oral glucose-lowering agents.The following parameters were evaluated at 0,and 24 weeks after the treatment: bodyweight,blood pressure,HbA1 c,fasting plasma glucose,fasting plasma insulin,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,triglycerides,estimated glomerular filtration rate and urinary albuminuria/creatinine ratio excretion.The primary outcome was changes in urinary albumin excretion at 24 weeks.Results :1 Significant and comparable falls in HbA1 c and fasting plasma glucose were found in both groups.2Saxagliptin significantly reduced NLrp3/ASC inflammasome within 24 weeks.3Saxagliptin significantly reduced urinary albumin excretion within 24 weeks.4 A total of 18 patients with normoalbuminuria showed a reduction in urinary albumin excretion,suggesting that saxagliptin prevents the development of albuminuria within 24 weeks.5A total of 38 patients with high urinary albuminuria/creatinine ratio showed a reduction in urinary albumin excretion,suggesting the beneficial effect of sitagliptin in the early stage of diabetic nephropathy within 24 weeks.6Saxagliptin has been associated with positive Effects on pancreatic ?-cell function and fasting plasma insulin within 24 weeks.7Saxagliptin increases estimated glomerular filtration rate and decreases Serum creatinine level within 24 weeks.8Saxagliptin significantly decreases diastolic blood pressure within 24 weeks.9There was a significant correlation between percentage changes of urinary albuminuria/creatinine ratio and that of NLrp3/ASC inflammasome within 24 weeks.10the Saxagliptin group showed no changes in HDL-C,but significant falls in LDL-C and TG within 24 weeks.11There are of upper respiratory tract infection,urinary tract infection,headache,cardiovascular events and so on serious adverse drug reactions such as hypoglycemic events was not found at saxagliptin group,there are 2 severe hypoglycemic events,3 abdominal distensions and 1nausea at other oral fall blood sugar medicine group within 24 weeks.Conclusions Research results show that Saxagliptin reduce the NLrp3/ASC inflammasome and urinary albumin/creatinine ratio and reduce fasting plasma glucose,glycosylated hemoglobin,and diastolic blood pressure increase the fasting plasma insulin secretion and improve the function of islet beta cells.one of the mechanisms reducing urinary albumin/creatinine ratio may inhibits the NLrp3 / ASC inflammasome.