Oriana Hoi Yun Yu

Objective: Polyendocrine metabolic ovarian syndrome (PMOS) is a multisystemic disorder with a wide range of health consequences. We sought to describe temporal trends in the prevalence and incidence of PMOS and to characterize its clinical presentation, comorbidity burden, and pharmacological management in primary care in the United Kingdom (UK) between 1998 and 2025. Design: Population‐based matched cohort study using primary care records from the UK Clinical Practice Research Datalink. Patients: Females newly diagnosed with PMOS between the ages of 15 and 49 matched on age, general practice, calendar year of cohort entry, and duration of medical history to population controls without PMOS. Measurements: Annual prevalence and incidence of diagnosed PMOS; baseline prevalence and incidence of cardinal PMOS features and various comorbidities; and pre‐ and post‐cohort entry prevalence of hormonal contraceptive, anti‐androgen, ovulation‐inducing drug, and metformin use. Results: The prevalence of diagnosed PMOS increased from < 0.1% in 1998 to 2.0% in 2025, with incidence rising from 0.1 to 3.6 per 1,000 person‐years over the same period. Among 125,482 patients with newly diagnosed PMOS matched with an equal number of controls, patients with PMOS had higher baseline prevalence and incidence of cardinal features of PMOS, as well as diabetes, dyslipidemia, hypertension, cardiovascular and cerebrovascular disease, sleep apnea, thyroid disorders, endometriosis, uterine fibroids, chronic pain, depression, and anxiety. Use of anti‐androgens, ovulation‐inducing drugs, and metformin was substantially higher in patients with PMOS, especially in the year following diagnosis. Conclusions: PMOS is increasingly diagnosed in UK primary care and is associated with substantial multimorbidity and pharmacotherapy.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for weight management, with a growing number of agents in the pipeline. This systematic review updates an earlier 2025 sy... Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for weight management. Purpose: To update our prior systematic review evaluating the efficacy and safety of G...

Subclinical hypothyroidism has been linked to adverse renal outcomes, but it is unknown whether treatment of subclinical hypothyroidism reduces the risk of these adverse outcomes. We sought to assess whether treatment of subclinical hypothyroidism with levothyroxine is associated with a decreased risk of developing adverse renal outcomes. We conducted a population-based cohort study using a prevalent new-user design. Using the Clinical Practice Research Datalink in the United Kingdom, we assembled a study cohort of individuals aged 18 years and older with newly diagnosed subclinical hypothyroidism between 1998 and 2018. We matched individuals with subclinical hypothyroidism treated with levothyroxine to nontreated individuals with subclinical hypothyroidism based on age, sex, calendar time, duration of subclinical hypothyroidism, and time-conditional propensity score. We included several confounders, including data on demographics, clinical diagnoses, biochemical measures, lifestyle, and prescriptions, in the time-conditional propensity score estimate. The primary outcome was a composite end point of end-stage renal disease (requiring dialysis) and lowering of the estimated glomerular filtration rate of 50% or greater. We matched 76 697 individuals with subclinical hypothyroidism treated with levothyroxine to 76 697 nontreated individuals. The mean age of the study cohort was 63 years, and 77% of patients were female. During a median follow-up time of 1.6 years (levothyroxine treated: 1.0, interquartile range [IQR] 0.4-2.7, yr; nontreated: 2.5, IQR 0.9-5.7, yr), 2426 adverse renal events occurred among nontreated individuals (incidence rate 8.35, 95% confidence interval [CI] 8.02-8.69, per 1000 person-years), and 1255 adverse renal events occurred among levothyroxine-treated individuals (incidence rate 7.93, 95% CI 7.50-8.39, per 1000 person-years). Treatment with levothyroxine was not associated with the risk of adverse renal outcomes among people with subclinical hypothyroidism (adjusted hazard ratio 0.97, 95% CI 0.90-1.04). In this population-based cohort study, there was no evidence that levothyroxine treatment of subclinical hypothyroidism reduced the risk of adverse renal outcomes. Future studies in different populations and with longer duration of follow-up are needed to confirm these findings.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), medications used to treat type 2 diabetes and obesity, are associated with delayed gastric emptying, which is a risk factor for gastroesophageal reflux disease (GERD). However, evidence linking these drugs to GERD is limited. To estimate the effect of GLP-1 RAs compared with sodium-glucose cotransporter-2 (SGLT-2) inhibitors on the risk for GERD and its complications among patients with type 2 diabetes. Active-comparator new-user cohort study emulating a target trial. U.K. Clinical Practice Research Datalink. Adults aged 18 years or older with type 2 diabetes initiating GLP-1 RAs or SGLT-2 inhibitors between 1 January 2013 and 31 December 2021, with follow-up until 31 March 2022. The primary outcome was incident GERD, and the secondary outcome was its complications. Three-year risk differences (RDs) and risk ratios (RRs) were estimated and weighted using propensity score fine stratification. The study included 24 708 new users of GLP-1 RAs and 89 096 new users of SGLT-2 inhibitors. Over a median follow-up of 3.0 years, the RRs were 1.27 (95% CI, 1.14 to 1.42) for GERD, with an RD of 0.7 per 100 patients, and 1.55 (95% CI, 1.12 to 2.29) for its complications, with an RD of 0.8 per 1000 patients, among GLP-1 RA users compared with SGLT-2 inhibitor users. Residual confounding due to lack of information on dietary or lifestyle factors. The estimated effect of GLP-1 RAs compared with SGLT-2 inhibitors suggested a higher risk for GERD and its complications in patients with type 2 diabetes. Clinicians should be aware of this potential adverse effect to provide timely prevention and treatment strategies. Canadian Institutes of Health Research.

Objective: To determine whether the use of glucagon-like peptide-1 (GLP-1) receptor agonists is associated with an increased risk of suicidal ideation, self-harm, and suicide among patients with type 2 diabetes compared with the use of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Design: Active comparator, new user cohort study. Setting: Primary care practices contributing data to the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics Admitted Patient Care and Office for National Statistics Death Registration databases. Participants: Patients with type 2 diabetes. Exposures: Two cohorts were assembled, with the first composed of patients who started and continued on GLP-1 receptor agonists or DPP-4 inhibitors between 1 January 2007 and 31 December 2020 and the second composed of patients who started and continued on GLP-1 receptor agonists or SGLT-2 inhibitors between 1 January 1 2013 and 31 December 2020. Both cohorts were followed until 29 March 2021. Main outcome measures: The primary outcome was suicidality, defined as a composite of suicidal ideation, self-harm, and suicide. Secondary outcomes were each of these events considered separately. Propensity score fine stratification weighted Cox proportional hazards models were fitted to estimate hazard ratios and 95% confidence intervals (CIs) to estimate the average treatment effect among the treated patients. Results: The first cohort included 36 082 GLP-1 receptor agonist users (median follow-up 1.3 years) and 234 028 DPP-4 inhibitor users (median follow-up 1.7 years). In crude analyses, GLP-1 receptor agonist use was associated with an increased incidence of suicidality compared with DPP-4 inhibitors (crude incidence rates 3.9 v 1.8 per 1000 person years, respectively; hazard ratio 2.08, 95% CI 1.83 to 2.36). This estimate decreased to a null value after confounding factors were accounted for (hazard ratio 1.02, 95% CI 0.85 to 1.23). The second cohort included 32 336 GLP-1 receptor agonist users (median follow-up 1.2 years) and 96 212 SGLT-2 inhibitor users (median follow-up 1.2 years). Similarly, GLP-1 receptor agonist use was associated with an increased risk of suicidality compared with SGLT-2 inhibitors in crude analyses (crude incidence rates 4.3 v 2.7 per 1000 person years; hazard ratio 1.60, 95% CI 1.37 to 1.87) but not after confounding factors were accounted for (0.91, 0.73 to 1.12). Similar findings were observed when suicidal ideation, self-harm, and suicide were analysed separately in both cohorts. Conclusions: In this large cohort study, the use of GLP-1 receptor agonists was not associated with an increased risk of suicidality compared with the use of DPP-4 inhibitors or SGLT-2 inhibitors in patients with type 2 diabetes.

Recent randomized controlled trials (RCTs) have investigated glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual or triple co-agonists for weight loss among adults with overweight or obesity and without diabetes. To assess the efficacy and safety of GLP-1 RAs and co-agonists for the treatment of obesity among adults without diabetes. MEDLINE, Embase, and Cochrane CENTRAL from inception to 4 October 2024. Placebo-controlled RCTs in otherwise healthy participants with overweight or obesity. The primary outcome was change in relative or absolute body weight from baseline to maximum on-treatment follow-up. Safety outcomes included death, serious adverse events (SAEs), any adverse events (AEs), and gastrointestinal AEs. A total of 26 RCTs comprising 15 491 participants (72% female; mean body mass index, 30 to 41 kg/m²; mean age, 34 to 57 years) and 12 agents (3 commercially available agents [liraglutide, semaglutide, and tirzepatide] and 9 premarket agents for long-term weight management) were included. Treatment ranged from 16 to 104 weeks (median, 43 weeks). Compared with placebo, tirzepatide (15 mg once weekly) resulted in weight loss of up to 17.8% (95% CI, 16.3% to 19.3%) after 72 weeks of therapy; semaglutide (2.4 mg once weekly), up to 13.9% (CI, 11.0% to 16.7%) after 68 weeks; and liraglutide (3.0 mg once daily), up to 5.8% (CI, 3.6% to 8.0%) after 26 weeks. Retatrutide (12 mg once weekly) produced greater weight loss of up to 22.1% (CI, 19.3% to 24.9%) after 48 weeks; other novel single and combination GLP-1 agents were also efficacious to varying degrees. Although AEs were frequent (GLP-1 RA vs. placebo: 80% to 97% vs. 63% to 100%), the majority were gastrointestinal-related (47% to 84% vs. 13% to 63%, respectively), most commonly nausea, vomiting, diarrhea, and constipation. AEs requiring treatment discontinuation (0% to 26% vs. 0% to 9%, respectively) and SAEs (0% to 10% vs. 0% to 12%, respectively) were rare. No head-to-head RCTs were available. Heterogeneity prevented meta-analysis. GLP-1 RAs and co-agonists are efficacious for weight loss, with reported safety concerns predominantly gastrointestinal in nature, when used among adults with overweight or obesity and without diabetes. None. (PROSPERO: CRD42024505558).

Objectives: To assess the association between sodium-glucose co-transporter-2 inhibitor (SGLT-2i) use and the risk of incident dementia compared with dipeptidyl peptidase-4 inhibitors (DPP-4i) use among individuals with type 2 diabetes.Design: A population-based retrospective cohort study.Setting: The Clinical Practice Research Datalink (CPRD) Aurum database from the UK.Participants: Individuals with type 2 diabetes, aged 40 years or older, newly prescribed SGLT-2i or DPP-4i on or after 2013–2021, registered in the CPRD Aurum database.Main outcome measure: The primary outcome was incident dementia, and the secondary outcome was incident mild cognitive impairment (MCI). Cox proportional hazard models were used to estimate the HR and corresponding 95% CI for the primary and secondary outcomes. Propensity score fine stratification weights were used to adjust for confounding.Results: Among a cohort of 118 006 individuals, the incident rate (IR) of dementia was 0.56/1000 person-years over a median follow-up period of 1.54 years among SGLT-2i users compared with 2.67/1000 person-years in DPP-4i users, over a median follow-up period of 1.79 years. The adjusted HR for SGLT-2i use compared with DPP-4i use for dementia was 0.78 (95% CI 0.55 to 1.12), while for MCI was 0.86 (95% CI 0.80 to 0.92). The age-specific stratified analysis demonstrated the adjusted HR for SGLT-2i use compared with DPP-4i use for the risk of incident dementia among elderly, aged ≥65 years, was 0.50 (95% CI 0.31 to 0.80).Conclusion: Primary findings did not yield conclusive evidence to infer an association between SGLT-2i use and the risk of incident dementia.