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Aim: To examine the cost‐effectiveness of adding canagliflozin or dapagliflozin to standard of care (SoC) versus SoC alone in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Materials and Methods: We used a Markov microsimulation model to assess the cost‐effectiveness of canagliflozin plus SoC (canagliflozin + SoC), dapagliflozin plus SoC (dapagliflozin + SoC) and SoC alone. Analyses were conducted from a healthcare system perspective. Costs were measured in 2021 Canadian dollars (C$), and effectiveness was measured in quality‐adjusted life‐years (QALYs). Results: Over a patient's lifetime, canagliflozin + SoC and dapagliflozin + SoC yielded cost savings of C$33 460 and C$26 764 and generated 1.38 and 1.44 additional QALYs compared with SoC alone, respectively. While QALY gains with dapagliflozin + SoC were higher than those with canagliflozin + SoC, this strategy was also more costly with the incremental cost‐effectiveness ratio exceeding the willingness to pay threshold of C$50 000 per QALY. Dapagliflozin + SoC, however, generated cost savings and QALY gains compared with canagliflozin + SoC over shorter time horizons of 5 or 10 years. Conclusions: Dapagliflozin + SoC was not cost‐effective versus canagliflozin + SoC in patients with CKD and T2D over the lifetime horizon. However, adding canagliflozin or dapagliflozin to SoC was less costly and more effective relative to SoC alone for treatment of CKD and T2D. [ABSTRACT FROM AUTHOR]

Aim: To compare the relative efficacy of sodium‐glucose co‐transporter 2 inhibitors (SGLT‐2is), glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and non‐steroidal mineralocorticoid receptor antagonists (nsMRAs) in improving the cardiovascular and renal outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). Materials and Methods: We searched PubMed, Embase and Cochrane Library from inception through 25 November 2022. We selected randomized controlled trials that studied patients with CKD and T2D with a follow‐up of at least 24 weeks and compared SGLT‐2is, GLP‐1RAs and nsMRAs with each other and with placebo. Primary outcomes were major adverse cardiovascular events (MACE) and composite renal outcomes (CRO). Secondary outcomes were cardiovascular death, all‐cause death, stroke, myocardial infarction and heart failure hospitalization (HFH). A frequentist approach was used to pool risk ratios (RRs) with 95% confidence intervals (CIs). Results: Twenty‐nine studies with 50 938 participants for MACE and 49 965 participants for CRO were included. SGLT‐2is did not significantly reduce MACE but were associated with significantly lower risks of CRO compared with GLP‐1RAs (RR, 0.77; 95% CI, 0.64‐0.91; P =.003) and nsMRAs (RR, 0.78; 95% CI, 0.68‐0.90; P =.001). Compared with GLP‐1RAs and nsMRAs, SGLT‐2is significantly reduced risks of HFH by 31% (RR, 0.69; 95% CI, 0.55‐0.88; P =.002) and 22% (RR, 0.78; 95% CI, 0.63‐0.95; P =.016), respectively, but did not significantly reduce other secondary outcomes. There were no significant differences between GLP‐1RAs and nsMRAs in lowering all outcomes. Conclusions: SGLT‐2is were associated with better cardiorenal protection than GLP‐1RAs and nsMRAs in patients with CKD and T2D. [ABSTRACT FROM AUTHOR]

The association between proton pump inhibitor (PPI) use and dementia remains controversial. This cohort study re‐examines this issue, addressing shortcomings identified in previous publications using a population‐based and a high‐dimension propensity‐score matched cohort to follow patients for up to 22 years. Cox regression models using baseline characteristics, a lag period, and time‐varying variables were used to examine the risk of dementia by cumulative PPI exposure. High‐dose PPI users (> 180 days of use) had significantly higher risk of dementia in crude Cox models. After adjustment for medical diagnoses and prescription drug use, these associations disappeared. Among high‐dose users starting PPI therapy between 46 and 55 years old, the unadjusted hazard ratio (HR) was 1.55 (95% confidence interval (CI) 1.14, 2.10); the adjusted hazard ratio (aHR) was 1.10 (95% CI 0.80, 1.51). For high‐dose users starting therapy between 56 and 65 years, HR = 1.22 (95% CI1.03, 1.44); aHR = 0.99 (95% CI 0.83, 1.17). High‐dose users between the ages of 66 and 75 years had no association with the risk of dementia. The use of lag models or time‐varying parameters similarly found some association with dementia in crude, but not multivariable Cox models. Although high‐dose PPI users were more likely to develop dementia, they were more likely to be diagnosed with dementia risk factors, such as diabetes and cardiovascular disease, which are risk factors for dementia. Controlling for these conditions using multivariable models or a propensity‐score matched cohort eliminated this association. [ABSTRACT FROM AUTHOR]

Background: Serious adverse effects of fluoroquinolone antibiotics have been described for more than decade. Recently, several drug regulatory agencies have advised restricting their use in milder infections for which other treatments are available, given the potential for disabling and possibly persistent side effects. We aimed to describe variations in fluoroquinolone use for initial treatment of urinary tract infection (UTI), acute bacterial sinusitis (ABS), and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the outpatient setting across Canada.Methods: Using administrative health data from six provinces, we identified ambulatory visits with a diagnosis of uncomplicated UTI, uncomplicated AECOPD or ABS. Antibiotic exposure was determined by the first antibiotic dispensed within 5 days of the visit.Results: We identified 4,303,144 uncomplicated UTI events among 2,170,027 women; the proportion of events treated with fluoroquinolones, mostly ciprofloxacin, varied across provinces, ranging from 18.6% (Saskatchewan) to 51.6% (Alberta). Among 3,467,678 ABS events (2,087,934 patients), between 2.2% (Nova Scotia) and 11.2% (Ontario) were dispensed a fluoroquinolone. For 1,319,128 AECOPD events among 598,347 patients, fluoroquinolones, mostly levofloxacin and moxifloxacin, ranged from 5.8% (Nova Scotia) to 35.6% (Ontario). The proportion of uncomplicated UTI and ABS events treated with fluoroquinolones declined over time, whereas it remained relatively stable for AECOPD.Conclusions: Fluoroquinolones were commonly used as first-line therapies for uncomplicated UTI and AECOPD. However, their use varied widely across provinces. Drug insurance formulary criteria and enforcement may be a key to facilitating better antibiotic stewardship and limiting potentially inappropriate first-line use of fluoroquinolones. [ABSTRACT FROM AUTHOR]

Objective: Reports of amputations associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors have been inconsistent. We aimed to compare the risk of below-knee amputation with SGLT2 inhibitors versus dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes.Research Design and Methods: This multicenter observational study used administrative health care databases from seven Canadian provinces and the U.K. Incident SGLT2 inhibitor users were matched to DPP-4 inhibitor users using a prevalent new-user design and time-conditional propensity scores. Cox proportional hazards models were used to estimate site-specific adjusted hazard ratios (HR) and corresponding 95% CIs of incident below-knee amputation for SGLT2 inhibitor versus DPP-4 inhibitor users. Random effects meta-analyses were used to pool the site-specific results.Results: The study cohort included 207,817 incident SGLT2 inhibitor users matched to 207,817 DPP-4 inhibitor users. During a mean exposed follow-up time of 11 months, the amputation rate was 1.3 per 1,000 person-years among SGLT2 inhibitor users and 1.5 per 1,000 person-years among DPP-4 inhibitor users. The adjusted HR of below-knee amputations associated with SGLT2 inhibitor use compared with DPP-4 inhibitor use was 0.88 (95% CI 0.71-1.09). Similar results were obtained in stratified analyses by specific SGLT2 inhibitor molecule.Conclusions: In this large multicenter observational study, there was no association between SGLT2 inhibitor use and incident below-knee amputations among patients with type 2 diabetes compared with DPP-4 inhibitor use. While these findings provide some reassurance, studies with a longer duration of follow-up are needed to assess potential long-term effects. [ABSTRACT FROM AUTHOR]

Aim: To compare urosepsis rates in patients with type 2 diabetes treated using sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) with dipeptidyl peptidase‐4 inhibitors (DPP4i) in a real‐world setting. Methods: We conducted a matched cohort study using a prevalent new‐user design with time‐conditional propensity scores. New users of SGLT2i from seven Canadian provinces and the UK were matched to DPP4i users. The primary outcome was hospitalization with a diagnosis of urosepsis and the secondary outcome was Fournier's gangrene. Site‐specific hazard ratios for urosepsis comparing SGLT2i with DPP4i were estimated using Cox proportional hazards models and pooled using a random effects meta‐analysis. Results: We included 208 244 users of SGLT2i and 208 244 users of DPP4i. Among SGLT2i users, 42% initiated canagliflozin, 31% dapagliflozin and 27% empagliflozin. During a mean follow‐up of 0.9 years, patients initiating SGLT2i had a lower rate of urosepsis compared with those receiving DPP4i. The pooled adjusted hazard ratio was 0.58 (95% confidence interval [CI]: 0.42‐0.80). The incidence rates of Fournier's gangrene were numerically similar in SGLT2i (0.08 per 1000 person‐years; 95% CI: 0.05‐0.13) and DPP4i users (0.14; 95% CI: 0.09‐0.21). Conclusions: In this large, multi‐site study, we did not observe an increased risk for urosepsis associated with SGLT2i compared with DPP4i among patients with type 2 diabetes in a real‐world setting. [ABSTRACT FROM AUTHOR]