Drug-Drug Interaction of the Sodium Glucose Co-Transporter 2 Inhibitors with Statins and Myopathy: A Disproportionality Analysis Using Adverse Events Reporting Data.

INTRODUCTION: An increased risk of myopathy due to a potential interaction between sodium glucose co-transporter-2 inhibitors (SGLT-2i) and HMG-CoA reductase inhibitors (statins) has been suggested by case reports. OBJECTIVE: We aimed to assess if the reporting of myopathy is disproportionally higher among people using both SGLT-2i and statins compared to using either SGLT-2i or statins alone. METHODS: We conducted a disproportionality analysis using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). We included reports with at least one antihyperglycemic agent. We compared the proportion of myopathy cases to non-cases between those not using SGLT-2i or statins, using SGLT-2i only, statins only, or both. We calculated the reporting odds ratio and 95% confidence interval. We further stratified by individual SGLT-2i and selected statins (rosuvastatin or atorvastatin). RESULTS: We included 688,388 reports with at least one antihyperglycemic agent recorded, of which 9.80% had at least one SGLT-2i agent. Among all included reports, there were a total of 2202 myopathy cases with the majority, 61.26%, occurring among those using statins alone and only 2.72% of myopathy cases were among those using both SGLT-2i and statins together. Reporting of myopathy was not disproportionally higher among those reporting the use of SGLT-2i with statins (reporting odds ratio 2.95, 95% confidence interval 2.27-3.85) compared to statins alone (reporting odds ratio 6.41, 95% confidence interval 5.86-7.02). CONCLUSIONS: Reports of myopathy were not disproportionally higher among those using SGLT-2i with statins compared to SGLT-2i or statins alone at the class level. Further observational studies may be needed to better assess this interaction at the agent level.

Adverse events associated with sodium glucose co-transporter 2 inhibitors: an overview of quantitative systematic reviews.

BACKGROUND: Multiple published quantitative systematic reviews have reported on adverse events associated with the use of sodium glucose co-transporter 2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus. AIMS: To summarize and appraise the quality of evidence from quantitative systematic reviews assessing adverse events of SGLT-2 inhibitors. METHODS: We searched PubMed, EMBASE and the Cochrane Library for quantitative systematic reviews assessing SGLT-2 inhibitor safety. Two reviewers extracted data and assessed methodological quality using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool. Main outcomes included pooled and single study point estimaates (in the absence of pooled estimates) with corresponding 95% confidence intervals (CIs) of SGLT-2 inhibitors versus placebo or active comparators for genitourinary infections, volume depletion, acute kidney injury, bone fractures, diabetic ketoacidosis, lower limb amputations, cancers, and other notable adverse events. RESULTS: Out of 1289 citations screened, 47 reviews assessed SGLT-2 inhibitor safety, of which 35 were of low quality. Canagliflozin, dapagliflozin and empagliflozin were consistently associated with an increased risk of genital tract infections versus placebo (point estimates ranged from 2.5 to 9.8) and other antihyperglycemic agents (point estimates ranged from 2.7 to 12.0). Canagliflozin and dapagliflozin were associated with an increased risk of diabetic ketoacidosis. Canagliflozin was the only agent associated with an increased amputation risk; however, this was driven by results from a single trial program. Dapagliflozin was the only agent that exhibited a statistically significant increased risk of urinary tract infections. Empagliflozin was associated with a statistically significant increased risk of bladder cancer; however, this finding was susceptible to detection bias. None of the agents were associated with a statistically significant increased risk of acute kidney injury, or bone fractures compared to placebo or mixed (active or placebo) comparators. Upper 95% CI limits do not rule out clinically meaningful outcomes. CONCLUSION: The majority of quantitative systematic reviews reporting on adverse events of SGLT-2 inhibitors were of low methodological quality. Despite almost 50 quantitative systematic reviews published on the safety of SGLT-2 inhibitors, clinicians are still left uncertain of the risks of important adverse effects. PLAIN LANGUAGE SUMMARY: SGLT-2 iInhibitor side effects: overview of reviews Many published systematic reviews have reported on side effects associated with the use of sodium glucose co-transporter 2 (SGLT-2) inhibitors in patients with type 2 diabetes. We aimed to summarize and appraise the quality of evidence from quantitative systematic reviews assessing side effects of SGLT-2 inhibitors. Using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool, two authors extracted data and assessed the methods of included reviews. Main outcomes included reported pooled and single study point estimates for several SGLT-2 inhibitor side effects such as genital infections, bone fractures, lower limb amputations, increased blood acidity, among others. Of the reviews included in our study, 35 of the 47 reviews assessed were of low quality. Canagliflozin and dapagliflozin were associated with an increased risk of blood acidity in a 2020 review. Canagliflozin was the only agent associated with an increased amputation risk; however, this was driven by results from a single trial program. Dapagliflozin was the only agent that exhibited a significantly increased risk of urinary tract infections. Empagliflozin was associated with an increased risk of bladder cancer; however, this finding was susceptible to bias. None of the agents were associated with an increased risk of kidney injury or bone fractures.

The association of sodium-glucose cotransporter 2 inhibitors with cancer: An overview of quantitative systematic reviews.

AIMS: To summarize reported cancer events associated with SGLT-2 inhibitors used in patients with type 2 diabetes mellitus, as well as assess the quality of included reviews. MATERIALS AND METHODS: In May 2019, we searched PubMed, Embase and the Cochrane Library for quantitative systematic reviews assessing the safety of SGLT-2 inhibitors. Data were abstracted using a standardized form, and methodological quality was assessed using the AMSTAR 2 tool. Main outcome measures included total cancer events and specific cancers such as breast cancer, bladder cancer, gastrointestinal cancer, prostate cancer, respiratory cancer, renal cancer and skin cancer. Pooled treatment effects from included reviews were summarized for SGLT-2 inhibitors as a class and for individual SGLT-2 inhibitors commonly used worldwide (canagliflozin, dapagliflozin and empagliflozin). RESULTS: We screened 1248 unique citations, of which eight quantitative systematic reviews meta-analysed results from studies reporting the association between an SGLT-2 inhibitor and any cancer. Only one review was rated as high quality according to AMSTAR 2 assessment. In total, data from 170 cancer-related point estimates (PE) were reported. As a class, SGLT-2 inhibitors were not associated with an increased risk of any cancer event versus placebo and active comparators. Most point estimates (7/143) were nonsignificant for individual cancers except for two associations. Empagliflozin was associated with an increased risk of bladder cancer versus placebo and active comparators in two reviews, while canagliflozin appeared protective for gastrointestinal cancer versus placebo and active comparators in one review. CONCLUSIONS: It appears that SGLT-2 inhibitors are not associated with an increased risk of total cancer or specific cancers in patients with type 2 diabetes. However, higher quality evidence is needed to derive confident conclusions.

High alert medications administration errors in neonatal intensive care unit: A pediatric tertiary hospital experience.

Labib JR, Youssef MRL, Abd El Fatah SAM. High alert medications administration errors in neonatal intensive care unit: A pediatric tertiary hospital experience. Turk J Pediatr 2018; 60: 277-285. Labib JR, Youssef MRL, Abd El Fatah SAM. High alert medications administration errors in neonatal intensive care unit: A pediatric tertiary hospital experience. Turk J Pediatr 2018; 60: 277-285. This is a hospital-based descriptive cross sectional study, implemented in the NICU, at Cairo University Pediatric hospital. A convenient sample of 33 bedside NICU nurses, who agreed to participate was recruited. A valid, reliable questionnaire was used to measure NICU nurses' general and specific knowledge regarding five therapeutic HAM. An observational checklist was used to assess nurses' administration practices. Both revealed that the mean percentage score of the nurses' knowledge (76.2±11.6) was higher than the mean percentage score of their total practice (69.1±13.3). Analysis of types of nurses' errors, showed that the most common error type was the wrong dose (15%), followed by wrong drug type (13.6%). Nurses' knowledge and training are not mandatorily interpreted into improved implementation practices. Interventions highlighted for preventing HAM errors were developing specific training on HAM for nurses and establishing neonate centered, multidisciplinary teams formed of physicians, nurses, and pharmacists.