Insulin and glucose-lowering agents for treating people with diabetes and chronic kidney disease.

backgroundDiabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co-exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD make glucose-lowering challenging, increasing the risk of hypoglycaemia. Glucose-lowering agents have been mainly studied in people with near-normal kidney function. It is important to characterise existing knowledge of glucose-lowering agents in CKD to guide treatment.

objectivesTo examine the efficacy and safety of insulin and other pharmacological interventions for lowering glucose levels in people with diabetes and CKD. SEARCH

methodsWe searched the Cochrane Kidney and Transplant Register of Studies up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs looking at head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in people with diabetes and CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m DATA COLLECTION AND ANALYSIS: Four authors independently assessed study eligibility, risk of bias, and quality of data and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). MAIN

resultsForty-four studies (128 records, 13,036 participants) were included. Nine studies compared sodium glucose co-transporter-2 (SGLT2) inhibitors to placebo; 13 studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; 2 studies compared glucagon-like peptide-1 (GLP-1) agonists to placebo; 8 studies compared glitazones to no glitazone treatment; 1 study compared glinide to no glinide treatment; and 4 studies compared different types, doses or modes of administration of insulin. In addition, 2 studies compared sitagliptin to glipizide; and 1 study compared each of sitagliptin to insulin, glitazars to pioglitazone, vildagliptin to sitagliptin, linagliptin to voglibose, and albiglutide to sitagliptin. Most studies had a high risk of bias due to funding and attrition bias, and an unclear risk of detection bias.Compared to placebo, SGLT2 inhibitors probably reduce HbA1c (7 studies, 1092 participants: MD -0.29%, -0.38 to -0.19 (-3.2 mmol/mol, -4.2 to -2.2); I AUTHORS'

conclusionsEvidence concerning the efficacy and safety of glucose-lowering agents in diabetes and CKD is limited. SGLT2 inhibitors and GLP-1 agonists are probably efficacious for glucose-lowering and DPP-4 inhibitors may be efficacious for glucose-lowering. Additionally, SGLT2 inhibitors probably reduce BP, heart failure, and hyperkalaemia but increase genital infections, and slightly increase creatinine. The safety profile for GLP-1 agonists is uncertain. No further conclusions could be made for the other classes of glucose-lowering agents including insulin. More high quality studies are required to help guide therapeutic choice for glucose-lowering in diabetes and CKD.