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Title: | Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients. | Authors: | Hawley C.M.;Toyama T.;Oshima M.;Jun M.;Chin K.L.;Zoungas S.;Lo C. | Monash Health Department(s): | Diabetes and Vascular Medicine | Institution: | (Lo, Chin, Zoungas) School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia (Toyama, Oshima, Jun, Zoungas) The George Institute for Global Health, UNSW, Sydney, Australia (Hawley) Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Australia (Lo, Zoungas) Diabetes and Vascular Medicine Unit, Monash Health, Clayton, Australia (Toyama, Oshima) Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan (Toyama, Oshima) Innovative Clinical Research Center (iCREK), Kanazawa University Hospital, Kanazawa, Japan (Chin) Melbourne Medical School, The University of Melbourne, Melbourne, Australia (Hawley) Australasian Kidney Trials Network, Diamantina Institute, The University of Queensland, Brisbane, Australia (Hawley) Translational Research Institute, Brisbane, Australia | Issue Date: | 19-Sep-2020 | Copyright year: | 2020 | Publisher: | John Wiley and Sons Ltd (E-mail: cs-journals@wiley.co.uk) | Place of publication: | United Kingdom | Publication information: | Cochrane Database of Systematic Reviews. 2020 (8) (no pagination), 2020. Article Number: CD009966. Date of Publication: 17 Aug 2020. | Journal: | Cochrane Database of Systematic Reviews | Abstract: | Background: Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017. Objective(s): To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation. Search Method(s): We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 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), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion. Data Collection and Analysis: Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). 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 Result(s): Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I2 = 49%; very low certainty evidence), delayed graft function (2 studies, 153 participants: RR 0.63, 0.42 to 0.93; I2 = 0%; very low certainty evidence), HbA1c (1 study, 16 participants; very low certainty evidence), fasting blood glucose (1 study, 24 participants; very low certainty evidence), kidney function markers (1 study, 26 participants; very low certainty evidence), death (any cause) (3 studies, 208 participants" RR 0.68, 0.29 to 1.58; I2 = 0%; very low certainty evidence), hypoglycaemia (4 studies, 301 participants; very low certainty evidence) and medication discontinuation due to adverse effects (1 study, 60 participants; very low certainty evidence). Compared to placebo, it is unclear whether DPP-4 inhibitors have an effect on hypoglycaemia and medication discontinuation (2 studies, 51 participants; very low certainty evidence). However, DPP-4 inhibitors may reduce HbA1c and fasting blood glucose but not kidney function markers (1 study, 32 participants; low certainty evidence). Compared to insulin glargine, it is unclear if DPP-4 inhibitors have an effect on HbA1c, fasting blood glucose, hypoglycaemia or discontinuation due to adverse events (1 study, 45 participants; very low certainty evidence). Compared to placebo, SGLT2 inhibitors probably do not affect kidney graft survival (1 study, 44 participants; moderate certainty evidence), but may reduce HbA1c without affecting fasting blood glucose and eGFR long-term (1 study, 44 participants, low certainty evidence). SGLT2 inhibitors probably do not increase hypoglycaemia, and probably have little or no effect on medication discontinuation due to adverse events. However, all participants discontinuing SGLT2 inhibitors had urinary tract infections (1 study, 44 participants, moderate certainty evidence). Compared to insulin therapy alone, it is unclear if glitazones added to insulin have an effect on HbA1c or kidney function markers (1 study, 62 participants; very low certainty evidence). However, glitazones may make little or no difference to fasting blood glucose (2 studies, 120 participants; low certainty evidence), and medication discontinuation due to adverse events (1 study, 62 participants; low certainty evidence). No studies of DPP-4 inhibitors, or glitazones reported effects on transplant or graft survival, delayed graft function or death (any cause). Authors' conclusions: The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1002/14651858.CD009966.pub3 | PubMed URL: | 32803882 [http://www.ncbi.nlm.nih.gov/pubmed/?term=32803882] | ISSN: | 1469-493X (electronic) | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/29050 | Type: | Review | Subjects: | drug safety *end stage renal disease/su [Surgery] estimated glomerular filtration rate glucose blood level *graft recipient graft survival human *insulin dependent diabetes mellitus/co [Complication] *insulin dependent diabetes mellitus/dt [Drug Therapy] insulin treatment intervention study *kidney transplantation *non insulin dependent diabetes mellitus/co [Complication] *non insulin dependent diabetes mellitus/dt [Drug Therapy] patient care postoperative period disease association priority journal review risk factor systematic review treatment outcome urinary tract infection/si [Side Effect] *empagliflozin/ae [Adverse Drug Reaction] *empagliflozin/ct [Clinical Trial] *empagliflozin/dt [Drug Therapy] *empagliflozin/tm [Unexpected Outcome of Drug Treatment] glucose/ec [Endogenous Compound] hemoglobin A1c/ec [Endogenous Compound] *insulin glargine/ct [Clinical Trial] *insulin glargine/cb [Drug Combination] *insulin glargine/dt [Drug Therapy] *pioglitazone/ct [Clinical Trial] *pioglitazone/cb [Drug Combination] *pioglitazone/dt [Drug Therapy] *sitagliptin/ct [Clinical Trial] *sitagliptin/dt [Drug Therapy] practice guideline drug efficacy drug safety end stage renal disease [Surgery] estimated glomerular filtration rate glucose blood level graft recipient graft survival insulin dependent diabetes mellitus/co insulin dependent diabetes mellitus insulin treatment intervention study kidney transplantation non insulin dependent diabetes mellitus/co non insulin dependent diabetes mellitus patient care postoperative period urinary tract infection empagliflozin [Adverse Drug Reaction] empagliflozin/ct empagliflozin glucose hemoglobin A1c insulin glargine/ct insulin glargine pioglitazone/ct pioglitazone sitagliptin/ct sitagliptin practice guideline drug efficacy intervention study *kidney transplantation *non insulin dependent diabetes mellitus / *complication / *drug therapy patient care postoperative period practice guideline priority journal Review risk factor systematic review treatment outcome urinary tract infection / side effect disease association *end stage renal disease / *surgery estimated glomerular filtration rate glucose blood level *graft recipient graft survival human *insulin dependent diabetes mellitus / *complication / *drug therapy insulin treatment drug efficacy drug safety |
Type of Clinical Study or Trial: | Systematic review and/or meta-analysis |
Appears in Collections: | Articles |
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