Sodium-Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia : A Population-Based Cohort Study.

BACKGROUND: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain. OBJECTIVE: To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA). DESIGN: Target trial emulation study. SETTING: Nationwide health care data of South Korea obtained from the National Health Insurance Service between 2010 and 2022. PATIENTS: Patients aged 60 years or older who have T2D and are initiating treatment with SGLT2 inhibitors or dulaglutide. MEASUREMENTS: The primary outcome was the presumed clinical onset of dementia. The date of onset was defined as the year before the date of dementia diagnosis, assuming that the time between the onset of dementia and diagnosis was 1 year. The 5-year risk ratios and risk differences comparing SGLT2 inhibitors with dulaglutide were estimated in a 1:2 propensity score-matched cohort adjusted for confounders. RESULTS: Overall, 12 489 patients initiating SGLT2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1075 patients initiating dulaglutide treatment were included. In the matched cohort, over a median follow-up of 4.4 years, the primary outcome event occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group. The estimated risk difference was -0.91 percentage point (95% CI, -2.45 to 0.63 percentage point), and the estimated risk ratio was 0.81 (CI, 0.56 to 1.16). LIMITATION: Residual confounding is possible; there was no adjustment for hemoglobin A1c levels or duration of diabetes; the study is not representative of newer drugs, including more effective GLP-1 RAs; and the onset of dementia was not measured directly. CONCLUSION: Under conventional statistical criteria, a risk for dementia between 2.5 percentage points lower and 0.6 percentage point greater for SGLT2 inhibitors than for dulaglutide was estimated to be highly compatible with the data from this study. However, whether these findings generalize to newer GLP-1 RAs is uncertain. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required. PRIMARY FUNDING SOURCE: Ministry of Food and Drug Safety of South Korea.

Risk of hepatic events associated with use of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists, and thiazolidinediones among patients with metabolic dysfunction-associated steatotic liver disease.

OBJECTIVE: To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). DESIGN: This population-based cohort study was conducted using a nationwide healthcare claims database (2014-2022) of Korea. We included individuals with MASLD (aged ≥40 years) who initiated SGLT-2i or comparator drugs (GLP-1RA or TZD). Primary outcome was a composite of hepatic decompensation events, including ascites, oesophageal varices with bleeding, hepatic failure or liver transplant. Liver-cause death and all-cause death were also assessed as secondary outcomes. Cox proportional hazards models were used to estimated HRs with 95% CIs. RESULTS: After 1:1 propensity score matching, we included 22 550 patients who initiated SGLT-2i and GLP-1RA (median age=57 years, 60% male), and 191 628 patients who initiated SGLT-2i and TZD (median age=57 years, 72% male). Compared with GLP-1RA, SGLT-2i showed a similar risk of hepatic decompensation events (HR 0.93, 95% CI 0.76 to 1.14). Compared with TZD, SGLT-2i demonstrated a reduced risk of hepatic decompensation events (HR 0.77, 95% CI 0.72 to 0.82). As compared with TZD, the results of secondary analyses showed significantly lower hepatic decompensation event risks with SGLT-2i when stratified by sex (male: HR 0.87 (95% CI 0.80-0.94); female: HR 0.62 (95% CI 0.55-0.69)). CONCLUSIONS: In this nationwide cohort study, SGLT-2i was associated with a lower risk of hepatic decompensation events in patients with MASLD compared with TZD, while demonstrating similar effectiveness to GLP-1RA.

Risk for Facial Palsy after COVID-19 Vaccination, South Korea, 2021-2022.

We conducted a self-controlled case series study to investigate the association between COVID-19 vaccination and facial palsy (FP) in South Korea. We used a large immunization registry linked with the national health information database. We included 44,564,345 patients >18 years of age who received >1 dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad.26.COV2.S) and had an FP diagnosis and corticosteroid prescription within 240 days postvaccination. We compared FP incidence in a risk window (days 1-28) with a control window (the remainder of the 240-day observation period, excluding any risk windows). We found 5,211 patients experienced FP within the risk window and 10,531 experienced FP within the control window. FP risk increased within 28 days postvaccination, primarily after first and second doses and was observed for both mRNA and viral vaccines. Clinicians should carefully assess the FP risk-benefit profile associated with the COVID-19 vaccines and monitor neurologic signs after vaccination.

Risk of encephalitis and meningitis after COVID-19 vaccination in South Korea: a self-controlled case series analysis.

BACKGROUND: Several neurological manifestations shortly after a receipt of coronavirus infectious disease 2019 (COVID-19) vaccine have been described in the recent case reports. Among those, we sought to evaluate the risk of encephalitis and meningitis after COVID-19 vaccination in the entire South Korean population. METHODS: We conducted self-controlled case series (SCCS) analysis using the COVID-19 immunization record data from the Korea Disease Control Agency between February 2021 and March 2022, linked with the National Health Insurance Database between January 2021 and October 2022. We retrieved all medical claims of adults aged 18 years or older who received at least one dose of COVID-19 vaccines (BNT162b2, mRNA-1273, ChAdOx1-S, or Ad26.COV2.S), and included only those who had a diagnosis record for encephalitis or meningitis within the 240-day post-vaccination period. With day 0 defined as the date of vaccination, risk window was defined as days 1-28 and the control window as the remainder period excluding the risk windows within the 240-day period. We used conditional Poisson regression to estimate the incidence rate ratios (IRR) with 95% confidence intervals (CI), stratified by dose and vaccine type. RESULTS: From 129,956,027 COVID-19 vaccine doses administered to 44,564,345 individuals, there were 251 and 398 cases of encephalitis and meningitis during the risk window, corresponding to 1.9 and 3.1 cases per 1 million doses, respectively. Overall, there was an increased risk of encephalitis in the first 28 days of COVID-19 vaccination (IRR 1.26; 95% CI 1.08-1.47), which was only significant after a receipt of ChAdOx1-S (1.49; 1.03-2.15). For meningitis, no increased risk was observed after any dose of COVID-19 vaccine (IRR 1.03; 95% CI 0.91-1.16). CONCLUSIONS: Our findings suggest an overall increased risk of encephalitis after COVID-19 vaccination. However, the absolute risk was small and should not impede COVID-19 vaccine confidence. No significant association was found between the risk of meningitis and COVID-19 vaccination.

Treatment Patterns and Persistence Among Patients Newly Diagnosed With Migraine in South Korea: A Retrospective Analysis of Health Claims Data.

BACKGROUND AND PURPOSE: Migraine is one of the most common chronic neurological diseases worldwide. Although diverse treatment regimens have been recommended, there is insufficient evidence for which treatment patterns to apply in routine clinical settings. METHODS: We used nationwide claims data from South Korea for 2015-2021 to identify incident migraine patients with at least one prescription for migraine. Patients were categorized according to their initial treatment classes and followed up from the date of treatment initiation. Treatment regimens included prophylactic treatments (antidepressants, anticonvulsants, beta blockers, calcium-channel blockers, and renin-angiotensin-aldosterone system [RAAS] inhibitors) and acute treatments (acetaminophen, antiemetics, aspirin, ergotamine, nonsteroidal anti-inflammatory drugs [NSAIDs], opioids, and triptans). The treatment patterns of migraine were evaluated until the end of the study period, including the secular trends, prevalence, persistence, and changes in migraine treatment. RESULTS: Among the 761,350 included patients who received migraine treatment, the most frequently prescribed acute treatment was an NSAID (69.9%), followed by acetaminophen (50.0%). The most-prescribed prophylactic treatment was flunarizine (36.9%), followed by propranolol (24.4%). Among the patients, 54.8% received acute treatment, 13.5% received prophylactic treatment, and 31.6% received both treatment types. However, 65.7% of the patients discontinued their treatment within 3 months. The 3-month persistence rate was highest for triptans (25.2%) among the acute treatments and for RAAS inhibitors (62.0%) among the prophylactic treatments. CONCLUSIONS: While the prevalence rates of medication use were found to align with current migraine guidelines, frequent switching and rapid discontinuation of drugs were observed in routine clinical settings.

Sodium-Glucose Cotransporter 2 Inhibitors vs Incretin-Based Drugs and Risk of Fractures for Type 2 Diabetes.

Importance: Postmenopausal individuals with type 2 diabetes are susceptible to fractures due to the interaction of elevated blood glucose levels and a deficiency of the hormone estrogen. Despite continued concerns of fracture risks associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i), existing evidence in this high-risk population is lacking. Objective: To assess the risk of fractures associated with SGLT2i vs incretin-based drugs of dipeptidyl-peptidase 4 inhibitors (DPP4i) and glucagon-like peptide 1 receptor agonists (GLP1RA), separately, in postmenopausal individuals with type 2 diabetes. Design, Setting, and Participants: This active-comparator, new-user cohort study used nationwide claims data of Korea and took place from January 1, 2013, to December 31, 2020. Postmenopausal individuals (aged ≥45 years) with type 2 diabetes were included. Exposures: New users of SGLT2i or comparator drugs. Main Outcomes and Measures: The primary outcome was overall fractures, comprising vertebral, hip, humerus, and distal radius fractures. Patients were followed up from the day after drug initiation until the earliest of outcome occurrence, drug discontinuation (90-day grace period) or switch, death, or end of the study period. After propensity score fine stratification, hazard ratios (HRs) with 95% CIs were estimated using weighted Cox models. Results: Among 37 530 (mean [SD] age, 60.6 [9.7] years) and 332 004 (mean [SD] age, 60.6 [9.9] years) new users of SGLT2i and DPP4i, respectively, a lower rate of incident overall fractures was presented with SGLT2i vs DPP4i (weighted HR, 0.78; 95% CI, 0.72-0.84). Among 111 835 (mean [SD] age, 61.4 [9.8] years) and 8177 (mean [SD] age, 61.1 [10.3] years) new users of SGLT2i and GLP1RA, respectively, no association with an increased risk of overall fractures was presented with SGLT2i vs GLP1RA (weighted HR, 0.92; 95% CI, 0.68-1.24). Results from several subgroup and sensitivity analyses presented consistent results from main analysis. Conclusions and relevance: This population-based cohort study suggests that SGLT2i was not associated with an increased rate of incident fractures compared with DPP4i and GLP1RA, separately, among postmenopausal individuals with type 2 diabetes.

Barriers to COVID-19 vaccine surveillance: the issue of under-reporting adverse events.

OBJECTIVES: This study investigated the reporting rates of adverse events following immunization (AEFIs) to the spontaneous reporting system (SRS) and its predictors among individuals with AEFIs after coronavirus disease 2019 (COVID-19) vaccination. METHODS: A cross-sectional, web-based survey was conducted from December 2, 2021 to December 20, 2021, recruiting participants >14 days after completion of a primary COVID-19 vaccination series. Reporting rates were calculated by dividing the number of participants who reported AEFIs to the SRS by the total number of participants who experienced AEFIs. We estimated adjusted odds ratios (aORs) using multivariate logistic regression to determine factors associated with spontaneous AEFIs reporting. RESULTS: Among 2,993 participants, 90.9% and 88.7% experienced AEFIs after the first and second vaccine doses, respectively (reporting rates, 11.6 and 12.7%). Furthermore, 3.3% and 4.2% suffered moderate to severe AEFIs, respectively (reporting rates, 50.5 and 50.0%). Spontaneous reporting was more prevalent in female (aOR, 1.54; 95% confidence interval [CI], 1.31 to 1.81); those with moderate to severe AEFIs (aOR, 5.47; 95% CI, 4.45 to 6.73), comorbidities (aOR, 1.31; 95% CI, 1.09 to 1.57), a history of severe allergic reactions (aOR, 2.02; 95% CI, 1.47 to 2.77); and those who had received mRNA-1273 (aOR, 1.25; 95% CI, 1.05 to 1.49) or ChAdOx1 (aOR, 1.62; 95% CI, 1.15 to 2.30) vaccines versus BNT162b2. Reporting was less likely in older individuals (aOR, 0.98; 95% CI, 0.98 to 0.99 per 1-year age increment). CONCLUSIONS: Spontaneous reporting of AEFIs after COVID-19 vaccination was associated with younger age, female sex, moderate to severe AEFIs, comorbidities, history of allergic reactions, and vaccine type. AEFIs under-reporting should be considered when delivering information to the community and in public health decision-making.