The incidence of diabetes is increasing year by year, and the statistics published by the International Diabetes Federation (IDF) on June 10, 2006 show that the number of people with diabetes has increased dramatically from 30 million to 230 million worldwide in the past 20 years. A recent epidemiological survey showed that the prevalence of diabetes in Chinese adults has reached 9.7%, or about 90 million people, and the prediabetes population is as high as 15.5%, or about 14 million people [1]. 2002 results from the Chronic Complications Survey Group of the Chinese Diabetes Association showed that the prevalence of diabetic kidney disease (DKD) can reach 33.6% [2]. In the United States, diabetes is the leading cause of kidney failure [3]. Since diabetes is a lifelong disease and glucose-lowering drugs need to be used for life, the safety of drug use is particularly important. How can patients with diabetes mellitus combined with kidney damage use glucose-lowering drugs rationally, without increasing the burden on the kidneys while lowering glucose rationally? A number of clinical studies have shown that intensive glucose lowering is effective in delaying the onset and progression of renal disease, and that lowering HbA1c to 7% is effective in reducing the incidence of microalbuminuria, reducing the development of massive proteinuria, and slowing the rate of decline in glomerular filtration rate (GFR). the ADA guidelines recommend that adults with diabetes should control HbAlc to <7% in the absence of severe hypoglycemia. HbA1c should be controlled as close to normal as possible. The incidence of hypoglycemia increases in patients with diabetic nephropathy once GFR decreases to chronic kidney disease (CKD) stages 3 to 5 (GFR < 60 ml/min) due to (1) decreased clearance of insulin and some oral hypoglycemic agents and (2) impaired renal glucose allogeneic function. Patients with type 2 diabetes have a lower risk of hypoglycemia compared to patients with type 1 diabetes. Therefore, we must closely monitor patients' blood glucose levels and reduce the dose of insulin and oral medications if necessary to avoid hypoglycemia. Different antidiabetic drugs have different requirements for use in patients with CKD stage 3 to 5 due to their different metabolic pathways and excretion routes. (1) Sulfonylureas. Sulfonylureas are mainly metabolized in the liver, and the drugs are excreted from the kidneys as prototypes or active metabolites. As renal function gradually decreases, the clearance of sulfonylureas also gradually decreases, so the drug dose should be reduced to avoid the occurrence of hypoglycemia. First-generation sulfonylureas such as chlorosulfonylurea and tolarsulfonylurea have been withdrawn from the historical stage and should be avoided in patients with CKD stage 3 to 5. Second-generation sulfonylureas (e.g., glibenclamide, glipizide, gliclazide, glimepiride, and gliquidone). Glibenclamide is mainly metabolized by the liver into two less active substances, one of which is 4 a hydroxy glibenclamide, which is 15% as active as glibenclamide, and is excreted through the kidneys, increasing the risk of hypoglycemia in patients with renal insufficiency, and thus should be avoided in patients with renal insufficiency. Glipizide is mainly cleared by hepatic biotransformation. Less than 10% of the dose of glipizide is excreted in the urine and feces in its original form, and about 90% of the dose is excreted in the urine (80%) and feces (10%) after biotransformation. The main metabolite of glipizide is the aromatic hydroxylation reaction product, which has no hypoglycemic activity. The incidence of hypoglycemia is low in patients with chronic renal insufficiency, and no dose adjustment is required for use in CKD stage 3-4 and dialysis patients. Gliclazide is rapidly absorbed in the gastrointestinal tract and metabolized by the liver to an inactive substance, which is generally considered to be used in chronic renal insufficiency. Glimepiride produces two metabolites via the liver, one of which is weakly active and eliminated via urine, increasing the risk of hypoglycemia in patients with renal insufficiency. 07 US Clinical Practice Guidelines for Diabetes and Chronic Kidney Disease recommend that the lowest dose of glimepiride starting in patients with CKD stages 3-4 and renal transplantation is 1 mg/day and is contraindicated in dialysis patients. All metabolites of glimepiride have little to no hypoglycemic activity, and more than 95% are excreted by the bile into the intestine. The metabolism of gliquidone is not altered in renal insufficiency, so it can still be taken when GFR< 60ml/min. (2) α-glucosidase inhibitors: The mechanism of action of these drugs is to reduce postprandial blood glucose by competitively inhibiting glucoamylase, sucrase and isogenic maltase at the brush border of the small intestinal mucosa, thereby delaying the absorption of glucose and fructose. The risk of hypoglycemia is relatively small with this class of drugs. Approximately <2% of acarbose in its original form or active metabolites are eliminated via the urine. There are no clinical studies related to the application of alpha glycosidase inhibitors in blood creatinine >2 mg/dL (>177 umol/L). Dose adjustment and monitoring of hepatic function should be observed in renal insufficiency and is contraindicated in patients with severe renal impairment (creatinine clearance ≤ (GFR ≤ 25 mL/Min). (3) Metformin: Metformin mainly improves glucose metabolism by restoring insulin inhibition of adenylate cyclase through hepatocyte membrane G protein, reducing hepatic gluconeogenesis and hepatic glucose output, promoting anaerobic glycolysis, increasing glucose uptake and utilization by peripheral tissues such as muscle, and inhibiting or delaying glucose absorption in the gastrointestinal tract. Hypoglycemia rarely occurs in patients taking metformin, and its main adverse effect is lactic acidosis. Metformin is cleared in its original form by the kidneys and may increase the risk of lactic acidosis by aggravating kidney damage. Therefore, metformin is contraindicated at GFR ≤ 60 mL/Min. (4) Glinide drugs: In glinide drugs, nateglinide is mainly metabolized by the liver, 83% is excreted from the kidney (of which 12%-14% is the original form of the drug), <10% is excreted from the feces, when the renal function is reduced, the active metabolites of nateglinide increase, so the dose should be reduced when using the drug in patients with CKD stage 3-4 and renal transplantation, and avoid using the drug in dialysis patients. In contrast, 92% of the metabolites of Repaglinide are excreted into the feces via the bile, and 8% of the metabolites are excreted into the urine via the kidneys, which has a rapid onset of action, short duration of action, and relatively little hypoglycemia. Pharmacogenetic studies have shown that patients with all stages of renal insufficiency have good tolerance for Repaglinide, and no dose adjustment is required for renal insufficiency and renal failure, but special care should be taken when adjusting the dose upward in patients with severe renal insufficiency. (5) Thiazolidinediones (TZDs): This class of drugs has the effect of reducing proteinuria, which may be related to the potent hypoglycemic effect of TZDs or to the decrease in blood pressure. These drugs are cleared by the liver, and their clearance is not reduced in patients with renal impairment. They do not increase the risk of hypoglycemia in patients with renal insufficiency, and no dose adjustment is required in chronic renal insufficiency, but there are potential side effects that lead to fluid retention, so they should be used with caution in patients with renal insufficiency. (6) Enteric-derived insulin secretagogues: This class of drugs includes ezenatide (GLP-l agonist) and cilastatin (DPP-4 inhibitor). The metabolites of exenatide are almost completely excreted by the kidneys, but no dose adjustment is necessary for creatinine clearance > 30 m L/min. in patients with CKD stage 4-5, the clearance of exenatide is substantially reduced, so its use is prohibited in this group of patients. Cilastatin is well tolerated, has a low incidence of hypoglycemia, and is excreted mainly in its original form via urine. The ADA recommends a 50% dose reduction (50 mg/day) when GFR < 50 mL?min-1? (1.73 m2 )-1 for 30 ≤ GFR and a 75% dose reduction (25 mg/day) when GFR < 30 mL?min-1? (1.73 m2 )-1. Some studies have now reported that GLP-1 can increase the incidence of acute renal tubular injury. (7) Insulin:Insulin is recommended for patients with diabetes mellitus with CKD stage 3 to 5. However, insulin dosage should be reduced in patients with advanced kidney disease. The American College of Physicians recommends that insulin dosage be reduced by 25% when GFR decreases to 10-50 ml/min and by 50% when it decreases to <10 ml/min. For hemodialysis patients who are prone to hypoglycemia during dialysis and hyperglycemia after dialysis, it is recommended to use sugar-containing dialysis solution when performing hemodialysis, and to apply dialysis solution containing 1 g/L glucose for regular dialysis treatment, and to relax the standard of blood glucose control, with fasting blood glucose level controlled at 8.25-11.1 mmol/L during the hemodialysis phase and 11.1-16.5 mmol/L 2 h after meal. ～It is safer to control the blood glucose level from 8.25 to 11.1 mmol/L during fasting and 11.1 to 16.5 mmol/L 2 hours after meal. Insulin should be reduced on the day of dialysis or a small amount of food should be eaten after the machine, which can avoid hypoglycemia due to the relative overdose of insulin. The insulin dose is increased after dialysis to prevent the occurrence of hyperglycemia. For the dose of insulin after peritoneal dialysis, the dose used after dialysis in foreign countries is 2 to 3 times the dose applied subcutaneously before dialysis. In conclusion, the glucose-lowering treatment for patients with diabetic kidney disease should take into account the effectiveness and safety of glucose-lowering treatment, and pay attention to self-monitoring of blood glucose throughout the treatment process. For diabetic patients with CKD stage 1 to 2, intensive glucose therapy can effectively delay the occurrence and development of diabetic nephropathy. For diabetic patients with CKD stage 3 to 5, the degree of kidney damage in patients with diabetic kidney disease should be correctly assessed and drugs should be reasonably selected. For dialysis patients, insulin is preferred for glucose-lowering treatment, and close attention should be paid to the changes of blood glucose during and after dialysis, and the insulin dose should be adjusted in time to prevent the occurrence of hypoglycemia or hyperglycemia pairs.