ABSTRACT
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.
Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Sodium-Glucose Transporter 2 Inhibitors , Humans , Cohort Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/complications , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Glucose/therapeutic use , Hypoglycemic Agents/therapeutic use , Retrospective Studies , Sodium , Sodium-Glucose Transporter 2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic useABSTRACT
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.
Subject(s)
Acute Kidney Injury , Diabetes Mellitus, Type 2 , Diabetic Ketoacidosis , Dipeptidyl-Peptidase IV Inhibitors , Sodium-Glucose Transporter 2 Inhibitors , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/chemically induced , Pharmacovigilance , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Diabetic Ketoacidosis/chemically induced , Diabetic Ketoacidosis/epidemiology , Diabetic Ketoacidosis/drug therapy , Adverse Drug Reaction Reporting Systems , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Chronic Disease , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Acute Kidney Injury/drug therapy , Glucose , SodiumABSTRACT
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.
Subject(s)
Asthma , Pneumonia , Pulmonary Disease, Chronic Obstructive , Humans , Drug Therapy, Combination , Administration, Inhalation , Asthma/diagnosis , Asthma/drug therapy , Asthma/chemically induced , Adrenal Cortex Hormones/therapeutic use , Hospitalization , Pneumonia/chemically induced , Pneumonia/diagnosis , Pneumonia/drug therapy , Gonadal Steroid Hormones , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/chemically induced , Adrenergic beta-2 Receptor Agonists/adverse effectsABSTRACT
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.
Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Reproductive Tract Infections , Sodium-Glucose Transporter 2 Inhibitors , Alberta , Cohort Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Glucagon-Like Peptide-1 Receptor/agonists , Glucose , Humans , Hypoglycemic Agents/adverse effects , Insulin/therapeutic use , Reproductive Tract Infections/chemically induced , Reproductive Tract Infections/complications , Reproductive Tract Infections/epidemiology , Sodium , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sulfonylurea CompoundsABSTRACT
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.
Subject(s)
Atrial Fibrillation , Hypertension , Stroke , Aged , Anticoagulants/adverse effects , Atrial Fibrillation/complications , Cross-Sectional Studies , Hemorrhage/etiology , Humans , Models, Statistical , Prognosis , Risk Assessment , Risk Factors , Stroke/etiologyABSTRACT
Evidence from observational studies may be considered complementary to that of randomized controlled trials (RCTs), particularly when assessing rare outcomes of drug therapies. Sodium/glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of antidiabetic agents that have been linked to an increased risk of diabetic ketoacidosis (DKA). We conducted a systematic review and separately meta-analyzed data from RCTs (n = 18; 2013-2019) and cohort studies (n = 7; 2017-2020) to assess the consistency of the magnitude of association between SGLT-2 inhibitors and DKA risk. We illustrate the strengths and weaknesses of the 2 designs. Results from RCTs and observational studies consistently showed almost a doubling in the risk of DKA among patients using an SGLT-2 inhibitor as compared with placebo or an active comparator. In a random-effects model, the pooled relative risk was 2.08 (95% confidence interval (CI): 1.28, 3.40) from placebo-controlled RCTs and 0.82 (95% CI: 0.25, 2.68) from active-comparator RCTs. The pooled adjusted hazard ratio from observational studies was 1.74 (95% CI: 1.28, 2.38). Notably, the 2 designs complement each other in several domains, including external and internal validity and power. This demonstrates a need for more comprehensive evidence when assessing rare adverse events for both sources.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetic Ketoacidosis/chemically induced , Hypoglycemic Agents/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Humans , Hypoglycemic Agents/therapeutic use , Observational Studies as Topic , Randomized Controlled Trials as Topic , Reproducibility of Results , Research Design , Risk Factors , Sodium-Glucose Transporter 2 Inhibitors/therapeutic useABSTRACT
OBJECTIVE: To determine the safety and effectiveness of current pharmacotherapies consisting of long-acting beta2-agonist (LABA) and/or inhaled corticosteroids (ICS) in patients with asthma-COPD overlap. DATA SOURCES: A systematic search was conducted using the PubMed, EMBASE, and Web of Science databases up to June 2018. STUDY SELECTIONS: Only studies comparing the safety and effectiveness of LABA and/or ICS in patients with asthma-COPD overlap were included. A meta-analysis was performed to calculate risk ratio (RR) and 95% confidence interval (CI) using Inverse Variance Random-effects model. RESULTS: From a total of 3382 articles retrieved, three randomized controlled trials (RCTs), six cohort studies (CS), one nested case control study fulfilled the inclusion criteria for three independent meta-analyses representing 181,603 participants. Three CS results show LABA was associated with decreased risk of myocardial infarction (combined RR: 0.80, 95% CI 0.74-0.87) versus non-LABA use; ICS/LABA was associated with a lower risk of death or hospitalization (combined RR: 0.82, 95% CI 0.75-0.90) compared to no use. Results from RCTs, no clear difference in lung function decline in FEV1 was found (combined mean difference: 0.08, 95% CI 0.15-0.32) in patients receiving ICS and/or LABA compared to placebo. However, due to lack of data, exacerbations, fractures and nontuberculous mycobacterial pulmonary disease outcomes were not meta-analyzed. CONCLUSIONS: Among patients with asthma-COPD overlap, LABA is associated with decreased risk of myocardial infarction; and the combination therapy of ICS/LABA appears to reduce the risk of death or hospitalization. More studies of quality data and larger number of patients are needed. REGISTRATION: PROSPERO (CRD42018090863).
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Adrenergic beta-2 Receptor Agonists/therapeutic use , Asthma/drug therapy , Bronchodilator Agents/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adrenergic beta-2 Receptor Agonists/adverse effects , Asthma/epidemiology , Asthma/physiopathology , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Delayed-Action Preparations , Disease Progression , Drug Therapy, Combination , Hospitalization/statistics & numerical data , Humans , Myocardial Infarction/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Function TestsABSTRACT
OBJECTIVE: The use of antipsychotics to treat seniors in long-term care facilities (LTCFs) has raised concern because of health consequences (i.e., increased risk of falls, stroke, death) in this vulnerable population. This study measured geographic patterns of antipsychotic utilization among seniors living in LTCFs in Newfoundland and Labrador (NL) and assessed potential inappropriateness. METHOD: We analyzed prescription records among adults 66 years and older with provincial prescription drug coverage admitted to LTCFs in NL between April 1, 2011, and March 31, 2014. Patterns of use were analyzed across the 4 regional health authorities (RHAs) in NL and LTCFs. Logistic, Poisson and linear regression models were used to test variations in prevalence, rate and volume of antipsychotic utilization. To assess potential inappropriateness of antipsychotic use, we analyzed data from Resident Assessment Instrument-Minimum Data Set (RAI-MDS) 2.0 forms from NL LTCFs between January 1, 2016, and December 31, 2018. Pearson chi-squared analysis was performed at the RHA and LTCF levels to determine changes in percentage of total prescriptions or antipsychotic prescriptions without psychosis. RESULTS: Between 2011 and 2014, 2843 seniors were admitted to LTCFs across NL; of these, 1323 residents were prescribed 1 or more antipsychotics. Within the 3-year period, the percentage of antipsychotic use across facilities ranged from 35% to 78%. Using data from 27,260 RAI-MDS 2.0 assessments between 2016 and 2018, 71% (6995/9851) of antipsychotic prescriptions were potentially inappropriate. DISCUSSION: There is substantial variation across NL regions concerning the utilization of antipsychotics for senior in LTCFs. Facility size and management styles may be reasons for this. CONCLUSION: With nearly three-quarters of antipsychotic prescriptions shown to be potentially inappropriate, systematic interventions to assess indications for antipsychotic use are warranted. Can Pharm J (Ott) 2021;154:xx-xx.
ABSTRACT
BACKGROUND: Prior meta-analyses measuring thiazide-induced glycemic change have demonstrated an increased risk of incident diabetes; however, this measure's definition has changed over time. AIM: To determine the magnitude of change in fasting plasma glucose (FPG) for thiazide diuretics. DATA SOURCES: A research librarian designed and conducted searches in Medline®, EMBASE, and EBM Reviews-Cochrane Central Register of Controlled Trials (inception through July 2018) and International Pharmaceutical Abstracts (inception to December 2014). STUDY SELECTION: Randomized, controlled trials comparing a thiazide or thiazide-like diuretic to any comparator reporting FPG were identified. Trials enrolling < 50 participants, those with a follow-up period of < 4 weeks, and conference abstracts were excluded. DATA EXTRACTION: Independent duplicate screening of citations and full-text articles, data extraction, and assessment of risk of bias was conducted. DATA SYNTHESIS: Ninety-five studies were included (N = 76,608 participants), with thiazides compared with placebo, beta-blockers, calcium channel blockers, renin-angiotensin-aldosterone-system inhibitors, potassium-sparing diuretic, and others alone or in combination. Thiazide diuretics marginally increased FPG (weighted mean difference 0.20 mmol/L (95% CI 0.15-0.25); I2 = 84%) (1 mmol/L = 18 mg/dL). Results did not change substantially when considering dose or duration, comparing thiazides with placebo or an active comparator, or using thiazides as monotherapy or combination therapy, even when combined with a potassium-correcting agent. CONCLUSION: Thiazide diuretics have a small and clinically unimportant impact on FPG.
Subject(s)
Hypertension , Sodium Chloride Symporter Inhibitors , Antihypertensive Agents/therapeutic use , Blood Glucose , Diuretics , Fasting , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Randomized Controlled Trials as Topic , Sodium Chloride Symporter Inhibitors/adverse effectsABSTRACT
BACKGROUND: Choice of minimum legal age (MLA) for cannabis use is a critical and contentious issue in legalization of non-medical cannabis. In Canada where non-medical cannabis was recently legalized in October 2018, the federal government recommended age 18, the medical community argued for 21 or even 25, while public consultations led most Canadian provinces to adopt age 19. However, no research has compared later life outcomes of first using cannabis at these different ages to assess their merits as MLAs. METHODS: We used doubly robust regression techniques and data from nationally representative Canadian surveys to compare educational attainment, cigarette smoking, self-reported general and mental health associated with different ages of first cannabis use. RESULTS: We found different MLAs for different outcomes: 21 for educational attainment, 19 for cigarette smoking and mental health and 18 for general health. Assuming equal weight for these individual outcomes, the 'overall' MLA for cannabis use was estimated to be 19 years. Our results were robust to various robustness checks. CONCLUSION: Our study indicated that there is merit in setting 19 years as MLA for non-medical cannabis.
Subject(s)
Legislation, Drug , Marijuana Smoking/legislation & jurisprudence , Adolescent , Canada , Humans , Marijuana Smoking/adverse effects , Surveys and Questionnaires , Young AdultSubject(s)
Dementia , Diabetes Mellitus, Type 2 , Hypoglycemia , Humans , Insulin/adverse effects , Mediation Analysis , Hypoglycemia/chemically induced , Hypoglycemia/prevention & control , Hypoglycemic Agents/adverse effects , Insulin, Regular, Human , Dementia/epidemiology , Dementia/etiology , Dementia/prevention & control , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapyABSTRACT
BACKGROUND: People with diabetes may be at higher risk for acquiring infections through both glucose-dependent and biologic pathways independent of glycemic control. Our aim was to estimate the association between diabetes and infections occurring in primary care. METHODS: Using the Newfoundland and Labrador Sentinel of the Canadian Primary Care Sentinel Surveillance Network, patients with diabetes ≥18 years between 1 January 2008 and 31 March 2013 were included with at least 1-year of follow-up. We randomly matched each patient with diabetes on the date of study entry with up to 8 controls without diabetes. Primary outcome was the occurrence of ≥1 primary care physician visits for any infectious disease. Secondary outcomes included primary visits for head & neck, respiratory, gastrointestinal, genitourinary, skin and soft tissue, musculoskeletal, and viral infections. Using multivariable conditional logistic regression analysis, we measured the independent association between diabetes and the occurrence of infections. RESULTS: We identified 1779 patients with diabetes who were matched to 11,066 patients without diabetes. Patients with diabetes were older, had a higher prevalence of comorbidities, and were more often referred to specialists. After adjusting for potential confounders, patients with diabetes had an increased risk of any infection compared to patients without diabetes (adjusted odds ratio = 1.21, 95% confidence interval 1.07-1.37). Skin and soft tissue infections had the strongest association, followed by genitourinary, gastrointestinal, and respiratory infections. Diabetes was not associated with head and neck, musculoskeletal, or viral infections. CONCLUSION: Patients with diabetes appear to have an increased risk of certain infections compared to patients without diabetes.
Subject(s)
Diabetes Mellitus/pathology , Infections/complications , Adult , Aged , Canada/epidemiology , Case-Control Studies , Cohort Studies , Diabetes Mellitus/epidemiology , Female , Follow-Up Studies , Humans , Infections/epidemiology , Logistic Models , Male , Middle Aged , Odds Ratio , Prevalence , Primary Health Care , Risk , Skin Diseases, Infectious/complications , Skin Diseases, Infectious/epidemiology , Soft Tissue Infections/complications , Soft Tissue Infections/epidemiologyABSTRACT
BACKGROUND: The pharmacokinetics and pharmacodynamics of antidiabetic therapies for patients with type 2 diabetes are often altered in the context of chronic kidney disease (CKD). STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Patients with type 2 diabetes and CKD. SELECTION CRITERIA FOR STUDIES: 2 reviewers independently screened studies identified through bibliographic databases (Cochrane Library, PubMed, Embase, International Pharmaceutical Abstracts), clinical trial registries, and references from pertinent articles and clinical practice guidelines. Eligible studies included randomized controlled trials evaluating incretin-based therapy in adults with type 2 diabetes and estimated glomerular filtration rates < 60mL/min/1.73m2. INTERVENTIONS: Incretin-based therapies (dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists) compared to placebo or active antidiabetic therapies. OUTCOMES: Changes in glycated hemoglobin (HbA1c), hypoglycemia, mortality, change in fasting plasma glucose, cardiovascular events, and end-stage renal disease. RESULTS: Of 1,619 nonduplicate records screened, 13 studies were included. Compared to placebo, incretin-based therapies significantly reduced HbA1c levels (n = 9; weighted mean difference, -0.64; 95% CI, -0.79 to -0.48; I2 = 43%); however, compared with active comparators, they did not (n = 4; weighted mean difference, -0.07; 95% CI, -0.25 to 0.12; I2 = 38%). Incretin-based therapies significantly increased the risk for hypoglycemia compared to placebo (n = 7; relative risk [RR], 1.38; 95% CI, 1.01-1.89; I2 = 0%) but no effect was observed versus active comparators (n = 4; RR, 0.24; 95% CI, 0.03-1.94; I2 = 52%). Limited evidence exists for all-cause mortality (placebo: n = 7 [RR, 1.21; 95% CI, 0.64-2.29; I2 = 0%]; active comparators: n = 3 [RR, 0.70; 95% CI, 0.32-1.54; I2 = 0%]). LIMITATIONS: Variation among interventions, small number of studies, heterogeneity between studies, and high risk for attrition bias in 7 of the selected studies. CONCLUSIONS: In patients with moderate or severe CKD, incretin-based therapies are effective in reducing HbA1c levels. Hypoglycemic events are rare, and wide CIs for the association preclude any definitive conclusions. Likewise, wide CIs were observed for mortality, cardiovascular events, and end-stage renal disease.
Subject(s)
Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/drug therapy , Incretins/therapeutic use , Renal Insufficiency, Chronic/complications , Humans , Incretins/adverse effects , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
OBJECTIVE: The aim of this study was to assess the impact of removing prior-authorization restrictions on the use of thiazolidinediones (TZDs) and outcomes. METHODS: In a controlled interrupted time-series analysis, whereby new users of antidiabetic agents over 65 years of age in adjacent Canadian provinces with different TZD-related policies [Alberta (n = 16,653) and Saskatchewan (n = 6682)] were followed from January 2001 to December 2006. Prior authorization for TZDs was removed in Alberta (intervention province) in December 2003 (rosiglitazone) and February 2004 (pioglitazone); no policy changes occurred in Saskatchewan (control province). Adjusted differences in percent change between intervention and control provinces were used to estimate policy-attributable effects (PAE) on TZD use within 30 days and 1 year and patient outcomes (composite of all-cause mortality or hospitalization for acute coronary events or heart failure) within 1 year. RESULTS: Mean age was 75 years, 51% were female, and 206,055 antidiabetic prescriptions were dispensed during follow-up. TZD use within 30 days among new users of antidiabetic agents increased almost >10% in Alberta compared with Saskatchewan controls immediately following the policy change: PAE = 9.4%, 95% confidence interval, 7.3%-11.6%. Other less expensive antidiabetic drug use decreased to exactly the same extent, suggesting TZD substitution. Compared with the controls, in Alberta there were no changes in the primary (clinical) composite outcome at 1 year (PAE = 0.31%, 95% confidence interval, -2.8% to +3.4%). CONCLUSIONS: The removal of a prior-authorization policy for TZDs was associated with an immediate increase in TZD use but did not impact patient outcomes. In this case, the policy removal shifted drug use to a more expensive drug with less certain clinical benefit.
Subject(s)
Hypoglycemic Agents/therapeutic use , Insurance, Health/organization & administration , Thiazolidinediones/therapeutic use , Aged , Alberta/epidemiology , Female , Health Policy , Humans , Male , Practice Patterns, Physicians'/statistics & numerical data , Saskatchewan/epidemiologyABSTRACT
Background: Clostridioides difficile is a pathogen causing diarrheal illness, which can be treated with vancomycin or fidaxomicin. Objective: To evaluate changes in monthly prescription volumes for oral vancomycin and fidaxomicin in Ontario community pharmacies following implementation of the 2017 and 2021 updates to guidelines from the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) and after a 2019 provincial formulary change for vancomycin. Methods: An interrupted time-series analysis was conducted from November 2015 to October 2021 using monthly projected prescription volumes obtained from IQVIA's Compuscript database. Level and slope (trend) changes in prescribing were assessed using segmented linear regression. Results: The volume of vancomycin prescriptions increased by 74 prescriptions per month (95% confidence interval [CI] 16 to 132) following implementation of the 2017 guideline update and by 73 prescriptions per month (95% CI 13 to 133) after the 2019 formulary change; however, no statistically significant changes were observed after implementation of the 2021 guideline update. No significant trend changes were observed for fidaxomicin. Conclusion: Guidelines and formulary changes were correlated with increased volume of vancomycin prescriptions.
Contexte: Le Clostridioides difficile est un agent pathogène provoquant une maladie diarrhéique pouvant être traitée avec de la vancomycine ou de la fidaxomicine. Objectif: Évaluer les changements de volume mensuel des prescriptions de vancomycine et de fidaxomicine par voie orale dans les pharmacies communautaires de l'Ontario après la mise en Åuvre des lignes directrices actualisées en 2017 et 2021 de l'Infectious Diseases Society of America (IDSA) et de la Society for Healthcare Epidemiology of America (SHEA) et à la suite d'une modification au régime d'assurance-médicaments pour la vancomycine à l'échelle provinciale en 2019. Méthodologie: Une analyse de séries chronologiques interrompues a été réalisée de novembre 2015 à octobre 2021 à l'aide des volumes mensuels de prescriptions projetés qui ont été obtenus grâce à la base de données Compuscript d'IQVIA. Les changements du volume des prescriptions et de son évolution dans le temps (le niveau et la pente, respectivement) ont été évalués à l'aide d'une régression linéaire segmentée. Résultats: Le volume des prescriptions de vancomycine a augmenté de 74 prescriptions par mois (intervalle de confiance [IC] à 95 % 16132) après la mise en Åuvre des lignes directrices actualisées en 2017; il a augmenté de 73 prescriptions par mois (IC à 95 % 13133) après la modification du régime d'assurance-médicaments de 2019; cependant, aucun changement statistiquement significatif n'a été observé après la mise en Åuvre des lignes directrices actualisées en 2021. Aucun changement significatif de tendance n'a été observé pour la fidaxomicine. Conclusion: Les lignes directrices et les modifications du régime d'assurance-médicaments étaient corrélées à une augmentation du volume des prescriptions de vancomycine.
ABSTRACT
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.
Subject(s)
Antipsychotic Agents , COVID-19 , Dementia , Humans , Female , Aged, 80 and over , Male , Antipsychotic Agents/therapeutic use , Anticonvulsants/therapeutic use , Analgesics, Opioid/therapeutic use , Pandemics , Nursing Homes , Cross-Sectional Studies , Psychotropic Drugs/therapeutic use , Antidepressive Agents/therapeutic use , Benzodiazepines/therapeutic use , Alberta , Dementia/drug therapy , Dementia/epidemiologyABSTRACT
PURPOSE: Administrative databases that only capture records for benefit-approved prescriptions may underestimate exposure because they do not capture non-benefit prescriptions. Using a natural experiment, we illustrate the impact of automating a prior-authorization policy on the completeness of drug exposure. METHODS: Using Saskatchewan (Canada) databases, weekly counts of benefit-approved and total prescription records in 2006 for new users of antidiabetic agents were examined across four categories: thiazolidinediones (TZDs), metformin, glyburide, and insulin. On July 1, 2006, Saskatchewan's public drug plan implemented an automated, online-adjudicated, prior-authorization process for TZDs; previously, prior approval was paper based. No such policy changes occurred for other drugs. We estimated the effect of this policy change on drug exposure using interrupted time-series analyses. RESULTS: We examined 223 552 prescription records: 19% were for TZDs, 48% for metformin, 20% for glyburide, and 13% for insulin. Prior to automation, there were, on average, 571 benefit-approved TZD records per week; however, the number of benefit-approved TZD records increased immediately after the automated process was introduced by 240 prescriptions per week (95% CI 200-280, p < 0.001). The average proportion of TZD benefit-approved records was 73% before and increased to 93% immediately following policy change (20% absolute change, 95% CI 18.7-20.4%). No changes were observed for metformin, glyburide, or insulin (p > 0.1 for all). CONCLUSIONS: Automating prior authorization for TZDs immediately increased the proportion of captured TZD records, suggesting in our study that one-fifth of TZD exposure was previously misclassified. If replicable, this indicates that even subtle changes in reimbursement policy may affect the validity of drug exposure data.
Subject(s)
Databases, Factual/statistics & numerical data , Hypoglycemic Agents/therapeutic use , Insurance, Pharmaceutical Services/statistics & numerical data , Reimbursement Mechanisms , Adult , Humans , Insurance Coverage/statistics & numerical data , Medical Records Systems, Computerized , Organizational Policy , Pharmacoepidemiology , Saskatchewan , Time FactorsABSTRACT
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.