Diabetic nephropathy how to choose hypoglycemic agents?

Type 2 diabetes is one of the most common chronic diseases, often associated with chronic kidney disease (CKD). The use of conventional doses of hypoglycemic agents will not only have some impact on renal function, but also may increase the risk of adverse reactions such as hypoglycemia, so patients should be specific for renal function, the rational choice of oral hypoglycemic agents. This paper summarizes the latest expert consensus and research for everyone to learn together.

1
Biguanides - to improve peripheral insulin resistance

Metformin was found to be excreted by the kidneys. Metformin and lactic acid were easily accumulated in the body when the renal function was severely impaired, increasing the risk of lactic acidosis. Based on the accumulation of clinical evidence, the US Food and Drug Administration (FDA) modified metformin in patients with nephropathy in the application of that metformin in mild renal impairment and some patients with moderate renal impairment in the safe application. At the same time, the American Diabetes Association (ADA) Diabetes Guidelines point out that metformin is safe for patients with an eGFR of 30 to 45 ml • min-1 • (1.73 m2) -1. But should reduce the dose of metformin and stop the use of the treatment of nausea, vomiting and dehydration drugs.

However, 2016 updated "type 2 diabetes with chronic kidney disease oral medicine principles of Chinese medicine experts consensus" mentioned in the eGFR <45 ml • min-1 • (1.73 m2) -1 when the application of metformin is still contraindicated, GFR <45 ml • min-1 • (1.73 m2) -1 is not recommended, GFR <30 ml • min-1 • (1.73 m2) -1 is disabled.

2
Sulfonylurea-insulin secretagogue

① glibenclamide: half-life and sustained action of a long time (10 ~ 16 h and 16 ~ 24 h), 50% of the active metabolites excreted by the kidneys, renal dysfunction in the accumulation of easily lead to severe hypoglycemia. CKD1 ~ 2 patients do not need to adjust the dose, 3 to 5 disabled;

Glimepiride: active metabolites and 60% of the prototype by renal excretion. CKD1 ~ 2 patients do not need to adjust the dose, 3a reduction, 3b ~ 5 disabled;

③ Glipizide: metabolites without hypoglycemic activity, mainly by renal excretion but lower risk of hypoglycemia than glibenclamide and glimepiride. CKD1 ~ 2 patients do not need to adjust the dose, 3 reduction, 4 to 5 disabled.

④ Gliclazide: metabolites without hypoglycemic activity, mainly by renal excretion but lower risk of hypoglycemia than glibenclamide and glimepiride. CKD1 ~ 2 patients do not need to adjust the dose, 3a with caution, 4 to 5 disabled.

⑤ gliquidone: metabolites inactive and mainly by fecal excretion, 5% by renal excretion. CKD1 ~ 3 patients do not need to adjust the dose, 4 with caution, 5 disabled.

3
Glibenclamide - non-sulfonylurea insulin secretagogue

① nateglinide: study found that moderate to severe CKD and hemodialysis patients, nateglinide plasma exposure was no significant change. Patients with CKD had no dose adjustment and GFR <30 ml · min-1 · (1.73 m)

② repaglinide: study found that compared with the normal group, repaglinide in CKD group blood pressure was no significant difference in the incidence of hypoglycemia and renal function damage has nothing to do. CKD1 ~ 5 patients do not need to adjust the dose, starting 0.5 mg per meal.

4
Thiazolidinediones - insulin sensitizers

① pioglitazone: the liver metabolism. CKD1 ~ 3a patients do not need to adjust the dose, 3b ~ 5 with caution.
② rosiglitazone: the liver metabolism. CKD patients do not need to adjust the dose.

5
Glycosidase inhibitors

① Acarbose: prototype and its metabolites in plasma concentration decreased significantly with renal function. CKD1 ~ 3 patients do not need to adjust the dose, 4 to 5 disabled;

② Voglibose: CKD 1 to 3 patients without adjusting the dose, 4 to 5 with caution.

6
Dipeptidyl peptidase-IV (DPP-4) inhibitor

① sitagliptin: about 79. 0% by renal excretion, plasma concentration decreased significantly with renal function decreased, and the prototype can be a small amount of dialysis to remove. GFR ≥50 ml • min-1 • (1.73m2) -1 was reduced to 50 mg once a day (qd) GFR <30 ml • min-1 • (1.73m2) -1 reduction to 25 mg qd;

② saxagliptin: by liver and kidney excretion. Mild CKD patients without adjusting the dose, moderate CKD reduction to 2.5 mg qd, severe CKD with caution;

③ vildagliptin: study found that patients with moderate or severe CKD, plasma vildagliptin plasma concentration increased about 2 times. Mild CKD patients without dose adjustment, moderate and severe reduction of CKD to 50 mg qd;

④ Glibenclamide: CKD patients do not need to adjust the dose;

⑤ Aglutin: 60% to 71% of the prototype by renal excretion. In patients with moderate CKD, the area under the plasma curve (AUC) of alogliptin increased approximately 2-fold. Patients with severe and end-stage CKD increased AUC by approximately 3 and 4-fold, respectively. (1.73m2) -1: 12.5mg / d, GFR <30 ml • min-1 • (1.73m2) -1: 6.25 mg / day for patients with mild CKD without dose adjustment, GFR 30-60 ml • min- / RTI & gt;