Safety and efficacy of glucagon-like peptide-1 receptor agonists among kidney transplant recipients: a systematic review and meta-analysis.

Background: Evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RAs) in kidney transplant recipients (KTRs) remains scarce. This systematic review and meta-analysis aims to evaluate the safety and efficacy of GLP-1RAs in this population. Methods: A comprehensive literature search was conducted in the MEDLINE, Embase and Cochrane databases from inception through May 2023. Clinical trials and observational studies that reported on the safety or efficacy outcomes of GLP-1RAs in adult KTRs were included. Kidney graft function, glycaemic and metabolic parameters, weight, cardiovascular outcomes and adverse events were evaluated. Outcome measures used for analysis included pooled odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes and standardized mean difference (SMD) or mean difference (MD) with 95% CI for continuous outcomes. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023426190). Results: Nine cohort studies with a total of 338 KTRs were included. The median follow-up was 12 months (interquartile range 6-23). While treatment with GLP-1RAs did not yield a significant change in estimated glomerular filtration rate [SMD -0.07 ml/min/1.73 m2 (95% CI -0.64-0.50)] or creatinine [SMD -0.08 mg/dl (95% CI -0.44-0.28)], they were associated with a significant decrease in urine protein:creatinine ratio [SMD -0.47 (95% CI -0.77 to -0.18)] and haemoglobin A1c levels [MD -0.85% (95% CI -1.41 to -0.28)]. Total daily insulin dose, weight and body mass index also decreased significantly. Tacrolimus levels remained stable [MD -0.43 ng/ml (95% CI -0.99 to 0.13)]. Side effects were primarily nausea and vomiting (17.6%), diarrhoea (7.6%) and injection site pain (5.4%). Conclusions: GLP-1RAs are effective in reducing proteinuria, improving glycaemic control and supporting weight loss in KTRs, without altering tacrolimus levels. Gastrointestinal symptoms are the main side effects.

Safety and Efficacy of GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus with Advanced and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Background and Objectives: Limited evidence exists regarding the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) patients with advanced chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Thus, we conducted a systematic review and meta-analysis to assess the safety and efficacy of GLP-1RAs in T2DM patients with advanced CKD and ESKD. Materials and Methods: We performed a systematic literature search in MEDLINE, EMBASE, and Cochrane database until 25 October 2023. Included were clinical trials and cohort studies reporting outcomes of GLP-1RAs in adult patients with T2DM and advanced CKD. Outcome measures encompassed mortality, cardiovascular parameters, blood glucose, and weight. Safety was assessed for adverse events. The differences in effects were expressed as odds ratios with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference or standardized mean difference (SMD) with 95% confidence intervals for continuous outcomes. The Risk of Bias In Non-randomized Studies-of Interventions (ROBIN-I) tool was used in cohort and non-randomized controlled studies, and the Cochrane Risk of Bias (RoB 2) tool was used in randomized controlled trials (RCTs). The review protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023398452) and received no external funding. Results: Eight studies (five trials and three cohort studies) consisting of 27,639 patients were included in this meta-analysis. No difference was observed in one-year mortality. However, GLP-1RAs significantly reduced cardiothoracic ratio (SMD of -1.2%; 95% CI -2.0, -0.4) and pro-BNP (SMD -335.9 pmol/L; 95% CI -438.9, -232.8). There was no significant decrease in systolic blood pressure. Moreover, GLP-1RAs significantly reduced mean blood glucose (SMD -1.1 mg/dL; 95% CI -1.8, -0.3) and increased weight loss (SMD -2.2 kg; 95% CI -2.9, -1.5). In terms of safety, GLP-1RAs were associated with a 3.8- and 35.7-time higher risk of nausea and vomiting, respectively, but were not significantly associated with a higher risk of hypoglycemia. Conclusions: Despite the limited number of studies in each analysis, our study provides evidence supporting the safety and efficacy of GLP-1RAs among T2DM patients with advanced CKD and ESKD. While gastrointestinal side effects may occur, GLP-1RAs demonstrate significant improvements in blood glucose control, weight reduction, and potential benefit in cardiovascular outcomes.

Diabetes Mellitus and Poor Glycemic Control Negatively Impact Clinical Outcomes and Survival in Patients with Compensated Cirrhosis.

Background and objectives: Diabetes mellitus (DM) increases morbidity and mortality in advanced cirrhosis. Information on the prognostic impact of DM in compensated cirrhosis is scarce. We aimed to explore the effect of DM and glycemic control on the natural history of compensated cirrhotic patients. Methods: This retrospective longitudinal cohort study included Child A/B cirrhosis without or free from decompensation or hospitalization > 1 year. Data on survival, unplanned hospitalization, hepatic decompensation (ascites, portal hypertension-related bleeding, hepatic encephalopathy, acute kidney injury), new infection, and hepatocellular carcinoma (HCC) were collected. Results: 457 patients were included (71.3% Child A, model for end-stage liver disease [MELD] 9.9 ± 3.1, alcohol/hepatitis B virus/hepatitis C virus 39.2%/21.7%/15.1%, 34.4% had DM). The cumulative overall survival was lower in DM group (75.7% vs. 86.5% at 10 yrs, P = 0.01). By multivariable Cox regression models adjusted with Child-Pugh and MELD score, DM was associated with higher mortality (hazards ratio [HR] 2.4, P = 0.014, and HR 2.03, P = 0.04, respectively). The cumulative incidences of unplanned hospitalizations (46.3% vs. 24.8% at 5 yrs, P < 0.001), hepatic decompensation (45% vs. 20.8% at 5 yrs, P < 0.001), new infection (47.2% vs. 20.2% at 5 yrs, P < 0.001), and HCC (29.3% vs. 16.8% at 10 yrs, P = 0.03) were higher in DM group. In patients with DM, 27.4% patients had poor glycemic control (HbA1c ≥7.0% for ≥80% of the study period). The cumulative overall survival was lower in poor glycemic control group (52.3% vs. 85.2% at 10 yrs, P = 0.02). By univariable Cox regression model, poor glycemic control was associated with higher mortality (HR 2.67, P = 0.025). Conclusions: In compensated cirrhosis, when coexisting with DM, the complications and mortality rates magnify. Poor glycemic control reduces survival in cirrhotic patients with DM. Proper diabetic screening and management should be emphasized in the care of these patients.

Metabolic complications of glucocorticoids - Prevention by metformin.

Glucocorticoid treatment is prescribed in 2 to 3% of the population for various diseases. Chronic exposure to excess glucocorticoid can lead to iatrogenic Cushing's syndrome, which is associated with increased morbidity, especially from cardiovascular diseases and infections. While several 'steroid-sparing' drugs have been introduced, glucocorticoid treatment is still applied in a large number of patients. We have previously showed that the enzyme AMPK plays a key role in mediating the metabolic effects of glucocorticoids. While metformin is the most widely used drug for treatment of diabetes mellitus, its mechanism of effect is still debated. Among several effects, it stimulates AMPK in peripheral tissue, affects the mitochondrial electron chain, influences gut bacteria and stimulates GDF15. We have hypothesised that metformin will counteract the metabolic effects of glucocorticoids, even in patients without diabetes. Two double-blind placebo-controlled randomised clinical studies were conducted: in the first, glucocorticoid-naive patients started metformin treatment early together with the glucocorticoid treatment. While in placebo group glycaemic indices worsened, these sequelae were prevented in the metformin group, suggesting a beneficial effect of metformin on glycaemic control in non-diabetic patients receiving glucocorticoid treatment. In the second study, we treated patients already on established glucocorticoid therapy for a longer period with metformin or placebo. In addition to the beneficial effects on glucose metabolism, we observed significant improvement in lipid, liver, fibrinolysis, bone and inflammatory parameters, as well as fat tissue and carotid intima media thickness. Moreover, patients had a lower risk of developing pneumonia and a reduced number of admissions to hospital, representing financial advantage for the health service. We believe that the routine use of metformin for patients on glucocorticoid treatment would represent a key advantage in the care for this patient population.

Effects of the Consumption of Low to Medium Glycemic Index-based Rice on the Rate of Insulin Initiation in Patients with Gestational Diabetes: A Triple-blind, Randomized, Controlled Trial.

INTRODUCTION: Medical nutritional therapy is vital in patients with diabetes. A low glycemic index (GI) is generally advised in the management of women with gestational diabetes mellitus (GDM). However, the efficacy of this advice has not been systematically examined. The purpose of this study was to determine whether recommending a low to moderate GI rice (RD43 rice; GI = 56.9) in women with GDM would reduce the number of women requiring insulin, compared with rice of high GI (Thai Hom Mali [THM] rice; GI = 80.1). METHODS: Ninety-six participants with GDM were randomly assigned to receive either RD43 rice or THM rice. RESULTS: The mean ± SD ages in the RD43 and THM groups were 33.1 ± 13.1 and 33.6 ± 4.1 years, respectively. The mean gestational ages at the sampling in the RD43 and THM groups were 23.3 ± 5.9 and 23.5 ± 5.4 weeks. Both groups had comparable baseline characteristics, including age, gestational age, body mass index prior to pregnancy and at enrollment, baseline postprandial (oral glucose tolerance test) plasma glucose level, and hemoglobin A1c. Of the 48 women assigned to the RD43 group, 3 (6.3%) required insulin; in the THM group, 11 (22.9%) met the criteria for insulin therapy (P = 0.017). However, 10 of these 11 women were able to avoid insulin use by changing to the low to moderate GI rice. CONCLUSION: Using a low to moderate GI rice in GDM effectively reduced the number of patients requiring insulin therapy. Thai Clinical Trials Registry ID: TCTR20210524007.

Implementation of diabetes care and educational program via telemedicine in patients with COVID-19 in home isolation in Thailand: A real-worldexperience.

BACKGROUND: The coronavirus disease (COVID-19) outbreak in Bangkok led to a shortage of hospital capacity, and a home isolation system was set up. We described the process of diabetes self-management education and support (DSMES) and glycemic management via telemedicine, along with outcomes in home-isolated patients with COVID-19 infection. METHODS: A retrospective chart review of glucose values, insulin and corticosteroids use, and outcomes was performed. RESULTS: A volunteer group of 21 endocrinologists and 21 diabetes educators/nurses formed the consultation team. Patients with diabetes or at high-risk of diabetes and receiving corticosteroids were referred by primary volunteer physicians. Glucometers and related supplies, and insulin were donated, and delivered via same-day delivery services. A chat group of an individual patient/their caregiver, diabetes educator, endocrinologist, and primary physician was formed (majority via LINE® platform) to assess the patient's clinical status and need. Real-time virtual DSMES sessions were performed and treatments were adjusted via smartphone application or telephone. There were 119 patients (1,398 service days), mean (SD) age 62.0 (13.6) years, 85.7% had a history of type 2 diabetes, and 84.0% received corticosteroids. Insulin was used in 88 patients; 69 of whom were insulin-naïve. During the first 10 days, there were 2,454 glucose values. The mean glucose level on day 1 was 280.6 (122.3) mg/dL, and declined to 167.7 (43.4) mg/dL on day 10. Hypoglycemia occurred in 1.4% of the values. A majority of patients (79.5%) recovered at home. CONCLUSION: Diabetes care and DSMES delivered via telemedicine to patients on home isolation during COVID-19 pandemic was safe and effective.