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

Lo C ，Toyama T ，Wang Y ，Lin J ，Hirakawa Y ，Jun M ，Cass A ，Hawley CM ，Pilmore H ，Badve SV ，Perkovic V ，Zoungas S ... -  《Cochrane Database of Systematic Reviews》

Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients.

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. 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. 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. 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. 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). 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). 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.

Lo C ，Toyama T ，Oshima M ，Jun M ，Chin KL ，Hawley CM ，Zoungas S ... -  《Cochrane Database of Systematic Reviews》

Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients.

Lo C ，Jun M ，Badve SV ，Pilmore H ，White SL ，Hawley C ，Cass A ，Perkovic V ，Zoungas S ... -  《Cochrane Database of Systematic Reviews》

Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.

Diabetes is associated with high risks of premature chronic kidney disease (CKD), cardiovascular diseases, cardiovascular death and impaired quality of life. People with diabetes are more likely to develop kidney impairment, and approximately one in three adults with diabetes have CKD. People with CKD and diabetes experience a substantially higher risk of cardiovascular outcomes. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors have shown potential effects in preventing kidney and cardiovascular outcomes in people with CKD and diabetes. However, new trials are emerging rapidly, and evidence synthesis is essential to summarising cumulative evidence. This review aimed to assess the benefits and harms of SGLT2 inhibitors for people with CKD and diabetes. We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2023 using a search strategy designed by an Information Specialist. Studies in the Register are continually identified through regular searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled studies were eligible if they evaluated SGLT2 inhibitors versus placebo, standard care or other glucose-lowering agents in people with CKD and diabetes. CKD includes all stages (from 1 to 5), including dialysis patients. Two authors independently extracted data and assessed the study risk of bias. Treatment estimates were summarised using random effects meta-analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The primary review outcomes were all-cause death, 3-point and 4-point major adverse cardiovascular events (MACE), fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and kidney failure. Fifty-three studies randomising 65,241 people with CKD and diabetes were included. SGLT2 inhibitors with or without other background treatments were compared to placebo, standard care, sulfonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, or insulin. In the majority of domains, the risks of bias in the included studies were low or unclear. No studies evaluated the treatment in children or in people treated with dialysis. No studies compared SGLT2 inhibitors with glucagon-like peptide-1 receptor agonists or tirzepatide. Compared to placebo, SGLT2 inhibitors decreased the risk of all-cause death (20 studies, 44,397 participants: RR 0.85, 95% CI 0.78 to 0.94; I2 = 0%; high certainty) and cardiovascular death (16 studies, 43,792 participants: RR 0.83, 95% CI 0.74 to 0.93; I2 = 29%; high certainty). Compared to placebo, SGLT2 inhibitors probably make little or no difference to the risk of fatal or nonfatal MI (2 studies, 13,726 participants: RR 0.95, 95% CI 0.80 to 1.14; I2 = 24%; moderate certainty), and fatal or nonfatal stroke (2 studies, 13,726 participants: RR 1.07, 95% CI 0.88 to 1.30; I2 = 0%; moderate certainty). Compared to placebo, SGLT2 inhibitors probably decrease 3-point MACE (7 studies, 38,320 participants: RR 0.89, 95% CI 0.81 to 0.98; I2 = 46%; moderate certainty), and 4-point MACE (4 studies, 23,539 participants: RR 0.82, 95% CI 0.70 to 0.96; I2 = 77%; moderate certainty), and decrease hospital admission due to heart failure (6 studies, 28,339 participants: RR 0.70, 95% CI 0.62 to 0.79; I2 = 17%; high certainty). Compared to placebo, SGLT2 inhibitors may decrease creatinine clearance (1 study, 132 participants: MD -2.63 mL/min, 95% CI -5.19 to -0.07; low certainty) and probably decrease the doubling of serum creatinine (2 studies, 12,647 participants: RR 0.70, 95% CI 0.56 to 0.89; I2 = 53%; moderate certainty). SGLT2 inhibitors decrease the risk of kidney failure (6 studies, 11,232 participants: RR 0.70, 95% CI 0.62 to 0.79; I2 = 0%; high certainty), and kidney composite outcomes (generally reported as kidney failure, kidney death with or without ≥ 40% decrease in estimated glomerular filtration rate (eGFR)) (7 studies, 36,380 participants: RR 0.68, 95% CI 0.59 to 0.78; I2 = 25%; high certainty) compared to placebo. Compared to placebo, SGLT2 inhibitors incur less hypoglycaemia (16 studies, 28,322 participants: RR 0.93, 95% CI 0.89 to 0.98; I2 = 0%; high certainty), and hypoglycaemia requiring third-party assistance (14 studies, 26,478 participants: RR 0.75, 95% CI 0.65 to 0.88; I2 = 0%; high certainty), and probably decrease the withdrawal from treatment due to adverse events (15 studies, 16,622 participants: RR 0.94, 95% CI 0.82 to 1.08; I2 = 16%; moderate certainty). The effects of SGLT2 inhibitors on eGFR, amputation and fracture were uncertain. No studies evaluated the effects of treatment on fatigue, life participation, or lactic acidosis. The effects of SGLT2 inhibitors compared to standard care alone, sulfonylurea, DPP-4 inhibitors, or insulin were uncertain. SGLT2 inhibitors alone or added to standard care decrease all-cause death, cardiovascular death, and kidney failure and probably decrease major cardiovascular events while incurring less hypoglycaemia compared to placebo in people with CKD and diabetes.

Natale P ，Tunnicliffe DJ ，Toyama T ，Palmer SC ，Saglimbene VM ，Ruospo M ，Gargano L ，Stallone G ，Gesualdo L ，Strippoli GF ... -  《Cochrane Database of Systematic Reviews》

Education programmes for people with chronic kidney disease and diabetes.

Adherence to complex regimens for people with chronic kidney disease (CKD) and diabetes is often poor. Interventions to enhance adherence require intensive education and behavioural counselling. However, whether the existing evidence is scientifically rigorous and can support recommendations for routine use of educational programmes in people with CKD and diabetes is still unknown. This is an update of a review first published in 2011. To evaluate the benefits and harms of education programmes for people with CKD and diabetes. We searched the Cochrane Kidney and Transplant Register of Studies up to 19 July 2024 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 Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. We included randomised controlled trials (RCTs) and quasi-RCTs investigating the benefits and harms of educational programmes (information and behavioural instructions and advice given by a healthcare provider, who could be a nurse, pharmacist, educator, health professional, medical practitioner, or healthcare provider, through verbal, written, audio-recording, or computer-aided modalities) for people 18 years and older with CKD and diabetes. Two authors independently screened the literature, determined study eligibility, assessed quality, and extracted and entered data. We expressed dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CI) and continuous data as mean difference (MD) with 95% CI. Data were pooled using the random-effects model. The certainty of the evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Eight studies (13 reports, 840 randomised participants) were included. The overall risk of bias was low for objective outcomes and attrition bias, unclear for selection bias, reporting bias and other biases, and high for subjective outcomes. Education programmes compared to routine care alone probably decrease glycated haemoglobin (HbA1c) (4 studies, 467 participants: MD -0.42%, 95% CI -0.53 to -0.31; moderate certainty evidence; 13.5 months follow-up) and may decrease total cholesterol (179 participants: MD -0.35 mmol/L, 95% CI -0.63 to -00.07; low certainty evidence) and low-density lipoprotein (LDL) cholesterol (179 participants: MD -0.40 mmol/L, 95% CI -0.65 to -0.14; low certainty evidence) at 18 months of follow-up. One study (83 participants) reported education programmes for people receiving dialysis who have diabetes may improve the diabetes knowledge of diagnosis, monitoring, hypoglycaemia, hyperglycaemia, medication with insulin, oral medication, personal health habits, diet, exercise, chronic complications, and living with diabetes and coping with stress (all low certainty evidence). There may be an improvement in the general knowledge of diabetes at the end of the intervention and at the end of the three-month follow-up (one study, 97 participants; low certainty evidence) in people with diabetes and moderately increased albuminuria (A2). In participants with diabetes and moderately increased albuminuria (A2) (one study, 97 participants), education programmes may improve a participant's beliefs in treatment effectiveness and total self-efficacy at the end of five weeks compared to routine care (low certainty evidence). Self-efficacy for in-home blood glucose monitoring and beliefs in personal control may increase at the end of the three-month follow-up (low certainty evidence). There were no differences in other self-efficacy measures. One study (100 participants) reported an education programme may increase change in behaviour for general diet, specific diet and home blood glucose monitoring at the end of treatment (low certainty evidence); however, at the end of three months of follow-up, there may be no difference in any behaviour change outcomes (all low certainty evidence). There were uncertain effects on death, serious hypoglycaemia, and kidney failure due to very low certainty evidence. No data was available for changes in kidney function (creatinine clearance, serum creatinine, doubling of serum creatinine or proteinuria). For an education programme plus multidisciplinary, co-ordinated care compared to routine care, there may be little or no difference in HbA1c, kidney failure, estimated glomerular filtration rate (eGFR), systolic or diastolic blood pressure, hypoglycaemia, hyperglycaemia, and LDL and high-density lipoprotein (HDL) cholesterol (all low certainty evidence in participants with type-2 diabetes mellitus and documented advanced diabetic nephropathy). There were no data for death, patient-orientated measures, change in kidney function (other than eGFR and albuminuria), cardiovascular disease morbidity, quality of life, or adverse events. Education programmes may improve knowledge of some areas related to diabetes care and some self-management practices. Education programmes probably decrease HbA1c in people with CKD and diabetes, but the effect on other clinical outcomes is unclear. This review only included eight studies with small sample sizes. Therefore, more randomised studies are needed to examine the efficacy of education programmes on important clinical outcomes in people with CKD and diabetes.

Cashmore BA ，Cooper TE ，Evangelidis NM ，Green SC ，Lopez-Vargas P ，Tunnicliffe DJ ... -  《Cochrane Database of Systematic Reviews》