Effect of the dual sodium-glucose co-transporter-1 and -2 inhibitor sotagliflozin on renal outcomes in type 1 diabetes and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

AIM: To investigate the renal safety profile of sotagliflozin, a novel sodium-glucose co-transporter-1 and -2 inhibitor, in patients with type 1 diabetes and type 2 diabetes, with or without renal impairment, as well as its efficacy in decreasing the risk of further renal events, with an emphasis on those with previous renal impairment. METHODS: Embase, Medline, CENTRAL and Scopus were searched from their inception until 24 April 2023 for randomized controlled trials that reported estimated glomerular filtration rate (eGFR), urinary albumin excretion or composite renal events (CRE). The Cochrane risk of bias 2 tool was used. Mean difference, relative risk (RR) and 95% confidence intervals were estimated (PROSPERO: CRD42023425583). RESULTS: Fourteen studies were included in this review (n = 17 574 participants; intervention n = 9312, control n = 8262). The median follow-up was 24.5 (Q1 = 15.25, Q3 = 28) months. Four studies recruited participants with renal impairment; baseline eGFR ranged from 23.8 to 50.5 mL/min/1.73m2 . The change in eGFR for studies (n = 6) with a follow-up of 52 weeks or longer was -1.23 (-1.45, -1.01) mL/min/1.73m2 . Sotagliflozin did not significantly alter urinary albumin excretion. No change was observed in the risk of CRE (n = 6 studies; RR = 0.82 [0.61, 1.12]), including in participants with renal impairment. High risk of bias was a limitation of this review. CONCLUSIONS: Sotagliflozin did not adversely affect renal function or change the risk of key renal outcomes, including for participants with pre-existing renal impairment. Therefore, sotagliflozin was safe; however, further research is needed to determine its efficacy in reducing the risk of diabetic kidney disease.

Drug exposure as a predictor in diabetic retinopathy risk prediction models; a systematic review and meta-analysis.

PURPOSE: To conduct a systematic review to assess drug exposure handling in diabetic retinopathy (DR) risk prediction models, a network-meta-analysis to identify drugs associated with DR and a meta-analysis to determine which drugs contributed to enhanced model performance. DESIGN: Systematic review and meta-analysis. METHODS: We included studies presenting DR models incorporating drug exposure as a predictor. We searched EMBASE, MEDLINE and SCOPUS from inception to December 2023. We evaluated the quality of studies using the Prediction model Risk of Bias Assessment Tool and certainty using GRADE. We conducted network meta-analysis and meta-analysis to estimate the odds ratio (OR) and pooled C-statistic, respectively, and 95% confidence intervals (CI) (PROSPERO: CRD42022349764). RESULTS: Of 5,653 records identified, we included 28 studies of 678,837 type 1 or 2 diabetes participants, of which 38,579 (5.7%) had DR. A total of 19, 3 and 7 studies were at high, unclear, and low risk of bias, respectively. Drugs included in models as predictors were: insulin (n=24), antihypertensives (n=5), oral antidiabetics (n=12), lipid-lowering drugs (n=7), antiplatelets (n=2). Drug exposure was modelled primarily as a categorical variable (n=23 studies). Two studies handled drug exposure as time-varying covariates, and one as a time-dependent covariate. Insulin was associated with an increased risk of DR (OR= 2.50; 95%-CI: 1.61-3.86). Models that included insulin (n=9) had a higher pooled C-statistic (C-statistic=0.84, CI: 0.80-0.88), compared to models (n=9) that incorporated a combination of drugs alongside insulin (C-statistic= 0.79, CI:0.74-0.84), as well as models (n=3) not including insulin (C-statistic =0.70, CI: 0.64-0.75). Limitations include the high risk of bias and significant heterogeneity in reviewed studies. CONCLUSION: This is the first review assessing drug exposure handling in DR prediction models. Drug exposure was primarily modelled as a categorical variable, with insulin associated with improved model performance. However, due to suboptimal drug handling, associations between other drugs and model performance may have been overlooked. This review proposes the following for future DR prediction models: 1) evaluation of drug exposure as a variable, 2) use of time-varying methodologies, and 3) consideration of drug regimen details. Improving drug exposure handling could potentially unveil novel variables capable of significantly enhancing the predictive capability of prediction models.

Peer-Led Versus Conventional Teacher-Led Methodological Research Education Sessions: An Initiative to Improve Medical Education Research Teaching.

Introduction: To enhance doctors' engagement with research, the National Medical Research Association (NMRA) developed a research teaching series, delivering peer-led (PL) sessions by medical students and conventional teacher-led (CL) sessions by licenced physicians/lecturers. We assessed the effectiveness of the series and compared the PL and CL approaches. Methods: The teaching sessions were delivered virtually via Zoom weekly either PL or CL. Feedback was provided by participants on completion of every session using a 10-point Likert scale assessing their knowledge pre- and post-training. Results: A total of 87 participants were included generating 782 feedback forms, 367 (47.1%) for PL and 412 for CL sessions. The median knowledge scores significantly increased following each session (p-value < 0.05) independent of teaching approach. An overall improvement in the median knowledge score from all sessions from 5/10 to 8/10 was reported. There was no significant difference between knowledge gained from the CL or PL teaching. Conclusion: Didactic PL research training sessions are equally effective as CL sessions.

Clinical Experience of a Long-acting Pegylated Erythropoietin-Stimulating Agent in Pediatric Chronic Kidney Disease.

OBJECTIVE: Management of anemia of chronic kidney disease (CKD) often includes subcutaneous or intravenous administration of erythropoietin-stimulating agents (ESAs). Mircera, a pegylated continuous erythropoietin receptor agonist, has a longer duration of action and requires less frequent administration than other ESAs. Pediatric experience with Mircera is limited. We retrospectively reviewed our long-term experience of Mircera in a national pediatric nephrology center. METHODS: Patients were identified via an electronic patient record database. Data collected included demographics (sex, age, etiology of CKD, CKD stage, dialysis modality), dosing information, and laboratory data-hemoglobin (Hb), parathormone (PTH), ferritin, hematinics prior to commencing Mircera and all subsequent values associated with dose adjustments. RESULTS: Seventy-seven patients aged 2 to 18 years, with CKD stages 2 to 5T had received at least 1 dose of Mircera, with 75 patients having sufficient data and a total of 1473 doses. No patients discontinued Mircera owing to adverse effects. One patient experienced a potential severe adverse drug reaction. Mircera was effective in improving or maintaining Hb ≥10.0 g/dL in most (58/75, 77.3%) patients. The median dose to achieve Hb ≥10.0 g/dL was 2.1 µg/kg/4 wk. Most doses (1039, 71.5%) were administered 4-weekly. The doses (161, 11.1%) that were administered 6-weekly remained efficacious. Thirty-two patients started Mircera with Hb <10.0 g/dL; 26 (81%) achieved Hb ≥10.0 g/dL within a median time of 4 months. Mircera was less effective if given every 8 weeks, or in the presence of hyperparathyroidism or hyperferritinemia. CONCLUSION: Mircera appears safe and effective in pediatric patients with CKD.