Psychotropic, Anticonvulsant, and Opioid Use in Assisted Living Residents Before and During the COVID-19 Pandemic.

OBJECTIVES: To examine the associations between COVID-19 pandemic waves (1-4) and prevalent antipsychotic, antidepressant, benzodiazepine, anticonvulsant, and opioid use among assisted living (AL) residents, by setting (dementia care vs other). DESIGN: Population-based, repeated cross-sectional study. SETTING AND PARTICIPANTS: Linked clinical and health administrative databases for residents of all publicly subsidized AL homes (N = 256) in Alberta, Canada, examined from January 2018 to December 2021. Setting-specific quarterly cohorts of residents were derived for pandemic (starting March 1, 2020) and comparable historical (2018/2019 combined) periods. METHODS: The quarterly proportion of residents dispensed an antipsychotic, antidepressant, benzodiazepine, anticonvulsant, or opioid was examined for each setting and period. Log-binomial generalized estimating equations models estimated prevalence ratios (PR) for period (pandemic vs historical quarterly periods), setting (dementia care vs other AL), and period-setting interactions. RESULTS: On March 1, 2020, there were 2874 dementia care and 6611 other AL residents (mean age 82.4 vs 79.9 years, 68.2% vs 66.1% female, 93.5% vs 42.6% with dementia, respectively). Antipsychotic use increased during waves 2 to 4 for residents of both settings, but this increase was significantly greater for dementia care than other AL residents during waves 3 and 4 (eg, wave 3, PR 1.21, 95% CI 1.14-1.27 vs PR 1.12, 95% CI 1.07-1.17, interaction term P = .029). In both settings, there was a significant but modest increase in antidepressant use and a significant decrease in benzodiazepine use during several pandemic waves. For other AL residents only, there was a small statistically significant increase in anticonvulsant use during waves 2 to 4. No significant pandemic effect was observed for prevalent opioid use in either setting. CONCLUSIONS AND IMPLICATIONS: The persistence of the pandemic-associated increase in antipsychotic, antidepressant, and anticonvulsant use in AL residents, and greater increase in antipsychotic use for dementia care settings, raises concerns about the attendant risks for residents, especially those with dementia.

Post-initiation predictors of discontinuation of the sodium-glucose cotransporter-2 inhibitors: A comparative cohort study from the United Kingdom.

AIMS: To assess post-initiation predictors of discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared to dipeptidyl-peptidase-4 (DPP-4) inhibitors in the United Kingdom. MATERIALS AND METHODS: We conducted a comparative population-based retrospective cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) with linked data to hospital and death records. We included new metformin users who initiated either SGLT2 inhibitors or DPP-4 inhibitors between January 2013 and October 2019. The main outcome was treatment discontinuation, defined as the first 90-day gap after the estimated treatment end date. We used a series of extended Cox models to assess which time-dependent predictors were associated with treatment discontinuation. To test if the hazard ratio of discontinuation for each predictor was statistically different between SGLT2 and DPP-4 inhibitors, an exposure-predictor interaction term was added to each model. RESULTS: There were 2550 new users of SGLT2 inhibitors and 8195 new users of DPP-4 inhibitors. Approximately 69% of SGLT2 inhibitor and 74% of DPP-4 inhibitor users had discontinued treatment by the end of follow-up. Occurrence of fractures after treatment initiation was a significant predictor of discontinuation of SGLT2 inhibitors (hazard ratio [HR] 4.13, 95% confidence interval [CI] 2.12-8.06) but not DPP-4 inhibitors (HR 0.93, 95% CI 0.79-1.11). The rate of treatment discontinuation was significantly higher for those with low estimated glomerular filtration rate and minimal contact with the healthcare system. Efficacy endpoints, such as heart failure and glycated haemoglobin level, were not associated with treatment discontinuation. CONCLUSIONS: Our findings reflect some discrepancy between the available evidence and prescribing behaviour for SGLT2 inhibitors.

Insulin Use in Type 2 Diabetes and the Risk of Dementia: A Comparative Population-Based Cohort Study.

OBJECTIVE: Evidence of an increased dementia risk with insulin use in type 2 diabetes is weakened by confounding by indication and disease severity. Herein we reassess this association, while accounting for confounding through design and analysis. RESEARCH DESIGN AND METHODS: Using administrative health care data from British Columbia, Canada, we identified patients diagnosed with type 2 diabetes in 1998-2016. To adjust for confounding by diabetes severity through design, we compared new users of insulin to new users of a noninsulin class, both from a restricted cohort of those who previously received two noninsulin antihyperglycemic classes. We further adjusted for confounding using 1) conventional multivariable adjustment and 2) inverse probability of treatment weighting (IPTW) based on the high-dimensional propensity score algorithm. The hazard ratio [HR] (95% CI) of dementia was estimated using cause-specific hazards models with death as a competing risk. RESULTS: The analytical comparative cohort included 7,863 insulin versus 25,230 noninsulin users. At baseline, insulin users were more likely to have worse health indicators. A total of 78 dementia events occurred over a median (interquartile range) follow-up of 3.9 (5.9) years among insulin users, and 179 events occurred over 4.6 (4.4) years among noninsulin users. The HR (95% CI) of dementia for insulin use versus noninsulin use was 1.68 (1.29-2.20) before adjustment and 1.39 (1.05-1.86) after multivariable adjustment, which was further attenuated to 1.14 (0.81-1.60) after IPTW. CONCLUSIONS: Among individuals with type 2 diabetes previously exposed to two noninsulin antihyperglycemic medications, no significant association was observed between insulin use and all-cause dementia.

Active-comparator restricted disproportionality analysis for pharmacovigilance signal detection studies of chronic disease medications: An example using sodium/glucose cotransporter 2 inhibitors.

AIMS: Disproportionality analysis is a common pharmacovigilance tool to detect safety signals of type 2 diabetes medications from spontaneous drug reporting databases. The aim was to demonstrate the impact of using active-comparator restricted disproportionality analysis (ACR-DA), wherein the reference group is restricted to reports with a clinically appropriate active comparator. METHODS: Using reports from the Food and Drug Administration Adverse Event Reporting System, we assessed if sodium/glucose cotransporter 2 (SGLT2) inhibitors are associated with higher reporting of 5 potential adverse events: acute kidney injury, genitourinary tract infections, diabetic ketoacidosis, fractures, and amputations. For each adverse event, we calculated the proportional reporting ratio (PRR) and adjusted reporting odds ratio (aROR [95% confidence interval, CI]) using 3 types of reference groups: no SGLT2 inhibitor (background risk reference), other diabetes drugs (therapeutic class reference), and dipeptidyl peptidase 4 inhibitors (active comparator reference). RESULTS: Based on ACR-DA, we did not detect a safety signal for acute kidney injury (PRR 0.92 [0.81-1.04]; aROR 0.78 [95% CI 0.72-0.85]) or fractures (PRR 0.44[95% CI 0.17-1.15]; aROR 0.74 [95% CI 0.61-0.91]) associated with SGLT2 inhibitors compared to dipeptidyl peptidase 4 inhibitors. However, we detected safety signals for genitourinary tract infections (PRR 2.75[2.02-3.76]; aROR 2.54[2.26-2.86], diabetic ketoacidosis (PRR 63.85[39.37-103.53; aROR 91.49[70.66-118.48]), and amputations (PRR 52.60 [19.66-140.75]; aROR 22.64 [15.32-33.42]. CONCLUSION: The use of the proposed ACR-DA to detect safety signals of type 2 diabetes medications may reduce false positive safety signals through careful selection of the comparator which is expected to reduce channelling bias.

Associations of Mid- and Late-Life Severe Hypoglycemic Episodes With Incident Dementia Among Patients With Type 2 Diabetes: A Population-Based Cohort Study.

OBJECTIVE: Severe hypoglycemia is associated with an increased risk of dementia. We examined if the association is consistently present in mid- and late-life hypoglycemia. RESEARCH DESIGN AND METHODS: Using health care data from Population Data BC, we created a base cohort of patients age ≥40 years with incident type 2 diabetes. Exposure was the first occurrence of severe hypoglycemia (hospitalization or physician visit). We assessed exposure versus no exposure in mid- (age 45-64 years) and late-life (age 65-84 years) cohorts. Index date was the later of the 45th birthday (midlife cohort), 65th birthday (late-life cohort), or diabetes diagnosis. Those with hypoglycemia or dementia before the index date were excluded. Patients were followed from index date until dementia diagnosis, death, emigration, or 31 December 2018. Exposure was modeled as time dependent. We adjusted for confounding using propensity score weighting. Dementia risk was estimated using cause-specific hazards models with death as a competing risk. RESULTS: Of 221,683 patients in the midlife cohort, 1,793 experienced their first severe hypoglycemic event. Over a median of 9.14 years, 3,117 dementia outcomes occurred (32 among exposed). Of 223,940 patients in the late-life cohort, 2,466 experienced their first severe hypoglycemic event. Over a median of 6.7 years, 15,997 dementia outcomes occurred (158 among exposed). The rate of dementia was higher for those with (vs. without) hypoglycemia in both the mid- (hazard ratio 2.85; 95% CI 1.72-4.72) and late-life (2.38; 1.83-3.11) cohorts. CONCLUSIONS: Both mid- and late-life hypoglycemia were associated with approximately double the risk of dementia, indicating the need for prevention throughout the life course of those with diabetes.

Prescribing Trends of the Sodium-Glucose Cotransporter-2 Inhibitors Among Different Physician Specialties in Canada (2015-2021).

OBJECTIVES: Landmark clinical trials have shown the sodium-glucose cotransporter-2 (SGLT-2) inhibitors to have cardiorenal benefits beyond their glucose-lowering effect. Clinical guidelines now recommend their use in patients with chronic kidney disease or heart failure, with or without type 2 diabetes, potentially affecting prescribing patterns among physician specialties. METHODS: Using monthly projected total retail dispensed prescription data from IQVIA's CompuScript database, we assessed trends in prescribing SGLT-2 inhibitors among 6 prescriber specialities from 2015 to 2021 in Canada. We assessed these trends at the class, agent, and dose level using joinpoint regression. RESULTS: From 2015 to 2021, the projected total retail dispensed prescriptions of SGLT-2 inhibitors from all prescribers increased. Relative to other prescribers, >60% of SGLT-2 inhibitor prescriptions were written by general practitioners or family physicians. The percentage of prescriptions from endocrinologists decreased (average annual percent change: mean, -10.8; 95% confidence interval [CI], -12.2% to -9.4%), whereas a dramatic increase was observed for cardiologists (mean, 44.1%, 95% CI, 32.9 to 56.2). The percentage from nephrologists also increased, albeit not statistically significant (mean, 12.4; 95% CI, -0.5 to 27.1). Significant changes in the agent and dose of SGLT-2 inhibitor prescribed were also observed among cardiologists and nephrologists. CONCLUSIONS: Between 2015 and 2021, there was a steady increase in the proportion of SGLT-2 inhibitor prescriptions from cardiologists and nephrologists, reflecting emerging evidence and guideline recommendations.

Hypoglycaemia and the risk of dementia: a population-based cohort study using exposure density sampling.

BACKGROUND: Previous studies have shown hypoglycaemia to be associated with an increased risk of dementia; however, there are several design challenges to consider. The objective of this study is to assess the association between hypoglycaemia and dementia while addressing these challenges using a lag period, exposure density sampling (EDS) and inverse probability of treatment weighting (IPTW). METHODS: This was a population-based cohort using data (1996-2018) from British Columbia, Canada. From a cohort of incident type 2 diabetes patients aged 40-70 years, we created a dynamic sub-cohort of hypoglycaemia-exposed (≥1 episode requiring hospitalization or a physician visit) and unexposed individuals using EDS, in which four unexposed individuals per one exposed were randomly selected into risk sets based on diabetes duration and age. Follow-up was until dementia diagnosis, death, emigration or 31 December 2018. Those diagnosed with dementia within 2 years of follow-up were censored. We adjusted for confounding using IPTW and estimated the hazard ratio (HR, 95% CI) of dementia using weighted conditional cause-specific hazards risk models with death as a competing risk. RESULTS: Among 13 970 patients with incident type 2 diabetes, 2794 experienced hypoglycaemia. There were 329 dementia events over a median (interquartile range: IQR) follow-up of 5.03 (5.7) years. IPTW resulted in well-balanced groups with weighted incidence rates (95% CI) of 4.59 (3.52, 5.98)/1000 person-years among exposed and 3.33 (2.58, 3.88)/1000 person-years among unexposed participants. The risk of dementia was higher among those with hypoglycaemia (HR, 1.83; 95% CI 1.31, 2.57). CONCLUSIONS: After addressing several methodological challenges, we showed that hypoglycaemia contributes to an increased risk of all-cause dementia among patients with type 2 diabetes.

Risk of all-cause mortality or hospitalization for pneumonia associated with inhaled ß2-agonists in patients with asthma, COPD or asthma-COPD overlap.

ß2-agonists provide necessary bronchodilatory action, are recommended by existing clinical practice guidelines and are widely prescribed for patients with these conditions. We examined the risk of all-cause mortality and hospitalization for pneumonia associated with long-or short-acting ß2-agonists (LABA or SABA) or ICS (inhaled corticosteroids)/LABA use. In a nested case-control of 185,407 patients, we found no association between ß2-agonist use and the risk of pneumonia in patients with asthma, COPD, or asthma-COPD overlap. In contrast, new SABA [HR 1.82 (95% CI 1.04-3.20)] or LABA [HR 2.77 (95% CI 1.22-6.31)] use was associated with an increased risk of all-cause mortality compared to ICS use in COPD patients.

Association between Inhaled ß2-agonists Initiation and Risk of Major Adverse Cardiovascular Events: A Population-based Nested Case-Control Study.

Purpose: Despite ample evidence underpinning the efficacy of ß2-agonists in asthma and chronic obstructive pulmonary disease (COPD), the occurrence of ß1- and ß2-adrenoceptors in the heart suggests that ß2-agonists may have deleterious cardiac effects. We investigated the association between new users of long-or short-acting ß2-agonists (LABA or SABA) or ICS (inhaled corticosteroids)/LABA and major adverse cardiovascular events (MACE). Methods: A nested case-control analysis was conducted using the UK Clinical Practice Research Datalink of patients with asthma, COPD or asthma-COPD overlap with initial treatment of LABA, SABA, ICS/LABA, ICS, long-or short-acting muscarinic antagonist (LAMA or SAMA) between 01 January 1998 and 31 July 2018. The primary outcome was MACE, defined as the first occurrence of stroke, heart failure, myocardial infarction, arrhythmia, or cardiovascular death. Each case was matched with up to 10 controls on age, sex, date of cohort-entry, and duration of follow-up. The risk of MACE associated with ß2-agonists was estimated using conditional logistic regression after controlling for potential confounders. Results: The cohort included 180,567 new users of ß2-agonists, ICS, SAMA, or LAMA. Among asthmatics, ß2-agonists were not associated with the risk of MACE (SABA vs ICS: HR 1.29 [0.96-1.73]; ICS/LABA vs ICS, HR 0.75 [0.33-1.73]). In contrast, among COPD patients, LABA (HR, 2.38 [1.04-5.47]), SABA (HR, 2.02 [1.13-3.59]) and ICS/LABA (HR, 2.08 [1.04-4.16]) users had an increased risk of MACE compared with SAMA users. Among patients with asthma-COPD overlap, SABA (HR, 2.57 [1.26-5.24]) was associated with an increased risk of MACE compared with ICS. Conclusion: In conclusion, initiation of LABA, SABA, or ICS/LABA in COPD or SABA in asthma-COPD overlap is associated with increased risk of MACE. No associations were observed among patients with asthma.

Sodium-Glucose Cotransporter-2 Inhibitors and Urinary Tract Infections: A Propensity Score-matched Population-based Cohort Study.

OBJECTIVES: Sodium-glucose cotransporter-2 (SGLT2) inhibitor-induced glycosuria is hypothesized to increase the risk of urinary tract infections (UTIs). We assessed the risk of UTIs associated with SGLT2 inhibitor initiation in type 2 diabetes. METHODS: We conducted a population-based cohort study using primary care data from the United Kingdom's Clinical Practice Research Datalink (CPRD) and administrative health-care data from Alberta, Canada. From a base cohort of new metformin users, we constructed 5 comparative cohorts, wherein the exposure contrast was defined as new use of SGLT2 inhibitors or 1 of 5 active comparators: dipeptidylpeptidase-4 (DPP-4) inhibitors, sulfonylureas (SU), glucagon-like peptide-1 receptor agonists (GLP-1 RA), thiazolidinediones (TZD) and insulin. We defined a composite UTI outcome based on hospitalizations or physician visit records. For each comparative cohort, we used high-dimensional propensity score matching to adjust for confounding and Cox proportional hazards regression to estimate the hazard ratios (HRs) in each database. We meta-analyzed estimates using a random-effects model. RESULTS: SGLT2 inhibitor use was not associated with a higher risk of UTI compared with DPP-4 inhibitors (pooled HR, 1.08; 95% confidence interval [CI], 0.89 to 1.30), SU (pooled HR, 1.08; 95% CI, 0.90 to 1.30), GLP-1 RA (pooled HR, 0.81; 95% CI, 0.61 to 1.09) or TZD (pooled HR, 0.81; 95% CI, 0.55 to 1.19). The risk of UTI was lower compared with insulin (pooled HR, 0.74; 95% CI, 0.63 to 0.87). The risk of UTI did not differ based on the SGLT2 inhibitor agent or dose. Last, SGLT2 inhibitor initiation was not associated with an increased risk of UTI recurrence. CONCLUSION: SGLT2 inhibitor use is not associated with an increased risk of UTIs, compared with other antidiabetic agents.

Trends and Determinants of Self-reported Aspirin Use Among Patients With Diabetes Stratified by Presence and Risk of Cardiovascular Diseases: A Repeated Pan-Canadian Cross-sectional Study.

OBJECTIVES: Our aim in this study was to quantify the prevalence over time and identify determinants of acetylsalicylic acid (ASA) use in patients with diabetes with and without cardiovascular disease (CVD) in a representative Canadian sample from 2005 to 2014, and to determine whether the use of ASA among patients with diabetes changed after the Diabetes Canada clinical practice guidelines updates. METHODS: Data from the Canadian Community Health Survey were used. Respondents who were at least 35 years of age and diagnosed with diabetes---not during pregnancy---were included and categorized into secondary prevention (previous heart disease or stroke) or primary prevention (high or low CVD risk) groups. A stratified and weighted multivariable logistic regression model was used to quantify ASA use and identify determinants of use. RESULTS: Our sample consisted of 15,100 respondents with diabetes (weighted sample of ∼2,429,900). Approximately 70% and 50% of Canadians with diabetes used ASA for secondary and primary prevention, respectively. Overall, the trend of ASA use was stable over the study period in both the secondary and the primary prevention groups. This trend did not change after the clinical practice guidelines update in 2008. Having a regular doctor and older age were associated with increased use of ASA. Other significant determinants independently associated with ASA use included income, body mass index, smoking, immigration status, gender and chronic diseases. CONCLUSIONS: Among patients with diabetes in Canada, ASA appears to be underutilized in secondary prevention and high-risk primary prevention populations. Future research should address whether regular use of ASA is associated with clinical outcomes among patients with diabetes.

Five comparative cohorts to assess the risk of genital tract infections associated with sodium-glucose cotransporter-2 inhibitors initiation in type 2 diabetes mellitus.

AIM: To assess the association between SGLT-2 inhibitors initiation and genital tract infections (GTIs) among patients with type 2 diabetes. METHODS: A population-based cohort study using administrative healthcare data from Alberta, Canada, and primary care data from the UK's Clinical Practice Research Datalink (CPRD). Among new metformin users, we identified new users of SGLT-2 inhibitors and five active comparator cohorts (new users of dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas (SU), glucagon-like peptide-1 receptor agonists (GLP-1 RA), thiazolidinediones (TZD) and insulin). The outcome of interest was a composite GTI outcome. In each cohort, we used high-dimensional propensity score matching to adjust for confounding and conditional Cox proportional hazards regression to estimate the hazard ratios (HR). We used random-effects meta-analysis to combine aggregate data across databases. RESULTS: The risk of GTI was higher for SGLT-2 inhibitors users compared with DPP4inhibitor users (pooled HR 2.68, 95% CI 2.19 3.28), SU users (3.29, 2.62-4.13), GLP1-RA users (2.51, 1.90-3.31), TZD users (4.17, 2.46-7.08) and insulin users (1.86, 1.27-2.73). CONCLUSION: In five comparative cohorts, SGLT-2 inhibitors initiation is associated with a higher risk of GTIs. These findings from real-world data are consistent with placebo-controlled randomized controlled trials.

Variation in bleeding risk estimates among online calculators: Cross-sectional study of apps used by and for patients with atrial fibrillation.

OBJECTIVE: To assess the variation in bleeding risk estimates and risk stratification among Web and mobile applications for patients with atrial fibrillation. DESIGN: Cross-sectional study. SETTING: Simulated patient population. PARTICIPANTS: Hypothetical patient cohorts that encompassed all possible binary risk factor combinations for each clinical prediction model. INTERVENTIONS: Twenty-five bleeding risk calculators (18 Web and 7 mobile apps), each of which used 1 of 4 clinical prediction models to predict an individual's 12-month bleed risk: ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), HAS-BLED (hypertension [systolic blood pressure >160 mm Hg], abnormal renal or liver function, stroke [caused by bleeding], bleeding, labile international normalized ratio, elderly [age >65 years], drugs [acetylsalicylic acid or nonsteroidal anti-inflammatory drugs] or alcohol [≥8 drinks per week]), HEMORR2HAGES (hepatic or renal disease, ethanol abuse, malignancy, older [age >75 years], reduced platelet count or function, rebleeding risk [history of past bleeding], hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke), and mOBRI (modified Outpatient Bleeding Risk Index). MAIN OUTCOME MEASURES: Four simulated cohorts were constructed. The coefficient of variation, relative difference (RD), and 95% CI for annual bleeding risk estimates were calculated for all hypothetical patient cohorts. Additionally, pairwise agreement between calculators across low- (<10%), moderate- (10% to 20%), and high-risk (>20%) categories of patients was determined. RESULTS: The risk estimates the calculators generated were imprecise, with coefficients of variation ranging from 14% for HEMORR2HAGES to 64% for mOBRI. Wide variation was observed in annual risk estimates for calculators using the mOBRI (maximum RD=4.3) and HAS-BLED (maximum RD=3.1) models. The 95% CI of mean annual bleeding risk varied among models; 1 calculator using the HAS-BLED model had a 95% CI of mean annual risk estimates of 5.4% to 6.2%, while another HAS-BLED calculator reported a 95% CI of 17.7% to 18.5%. Concordance for risk category stratification among calculators was high for those based on mOBRI and ATRIA (=1 for both). Poor agreement was observed in 1 calculator using HEMORR2HAGES (=0.54) and another using HAS-BLED ( range=-0.11 to 0.35). CONCLUSION: Inconsistencies and a lack of precision were observed in annual risk estimates and risk stratification produced by Web and mobile bleeding risk calculators for patients with atrial fibrillation. Clinicians should refer to annual bleeding risks observed in major randomized controlled trials to inform risk estimates communicated to patients.

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.

Risk of hospitalization and death associated with sodium glucose cotransporter-2 inhibitors: A comparison with five other classes of antidiabetic drugs.

AIM: We assessed the risk of all-cause hospitalization and all-cause death associated with the use of Sodium Glucose Cotransporter-2 inhibitors (SGLT2i). METHODS: Population-based propensity scores-matched cohort study of new users of metformin who subsequently initiated SGLT2i compared to those who initiated dipeptidyl peptidase-4 inhibitors (DPP4i) (primary comparison), sulfonylureas, thiazolidinediones, GLP1-Receptors agonists, and insulin, respectively. Alberta (Canada) health administrative data and United Kingdom Clinical Practice Research Datalink (CPRD) data were used to assess the study outcomes. Conditional Cox regressions were performed to assess the risk of each outcome, separately for each dataset and then results were combined using random-effects meta-analysis. RESULTS: For SGLT2i versus DPP4i, 7531 and 1647 SGLT2i-DPP4i matched pairs were analyzed in Alberta and CPRD data respectively. The mean age of patients was 56 and 57 years, and 39% and 43% were females, respectively in Alberta and CPRD cohorts. Compared with DPP-4-i, SGLT2i use was associated with a significant lower risk of all-cause hospitalization (combined hazard ratio (HR): 0.84, 95% confidence interval (95%CI): 0.75-0.95), and all-cause death (0.56, 0.38-0.83). SGLT2i use was also associated with a significant lower risk of all-cause hospitalization and all-cause death when compared to sulfonylureas (HRs: 0.80, 95%CI: 0.71-0.90 and 0.56, 95%CI: 0.38-0.82, respectively) and insulin (HRs: 0.55, 95%CI: 0.41-0.74, and 0.33, 95%CI: 0.24-0.46, respectively). CONCLUSIONS: SGLT2i initiation was associated with a decreased risk of all-cause hospitalization and all-cause death when compared to DPP4i, sulfonylureas, and insulin.

Peak performance: Putting type 1 diabetes management recommendations for athletes to the test.

Background: Athletes with type 1 diabetes (T1D) face unique challenges to maintain optimal glucose levels and therefore require tailored guidance from their healthcare providers. Herein, we aim to summarize and compare recommendations targeted at T1D management in athletes in commonly used clinical practice guidelines and topical position statements. The objective is to assess if the available recommendations are comprehensive enough for athletes to apply to high-performance sport. Methods: From seven clinical practice guidelines and positions statements, we identified recommendations relevant to athletes with T1D, based on a specific hierarchy. For included recommendations, we extracted relevant information including the year of publication, author(s), chapter name or number, text for the recommendation, and level of evidence. Based, on the clinical topic covered, we grouped included recommendations to five themes. Results: We screened a total of 126 recommendations, of which 60 recommendations were included. The National Athletic Trainers' Association provided the highest number of recommendations relevant to athletes with T1D (n = 27). Insulin modifications was the most covered clinical theme (n = 18). The 2018 Diabetes Canada and 2021 American Diabetic Association guidelines linked recommendations directly with levels and grades of evidence. None of the recommendations had level 1 or grade A evidence. Three recommendations from Diabetes Canada reported level 2, grade B evidence. American Diabetic Association reported 1 recommendation with grade B evidence, and 2 recommendations with grade C evidence. Conclusions: There is an opportunity for expansion of clinical practice guidelines to increase the depth and breadth of recommendations for high performance athletes with T1D.