The expanding role of GLP-1 receptor agonists: a narrative review of current evidence and future directions.

Unlabelled: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed obesity management, offering substantial weight loss and metabolic benefits. This review examines their expanding role, evaluating efficacy compared to alternative treatments, emerging indications, ongoing challenges, and future directions. Beyond obesity and type 2 diabetes, the therapeutic potential of GLP-1 RAs extends to a range of conditions such as cardiovascular disease, liver disease, neurodegenerative disease, and substance abuse disorders.

Levothyroxine treatment for subclinical hypothyroidism and risk of adverse renal outcomes: a population-based cohort study.

Background: 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.

Methods: We conducted a population-based cohort study using a prevalent new-user design.

The risk of bleeding in pregnant women with acute venous thromboembolism treated with anticoagulants: an international multidatabase cohort study.

Background: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism, is a major cause of maternal mortality. Low-molecular-weight heparin (LMWH) is the mainstay of therapy for VTE during pregnancy. However, the effects of different LMWH types and dosing regimens on bleeding risk remain unclear.

Core Concepts in Pharmacoepidemiology: Multi-Database Distributed Data Networks.

Multi-database distributed data networks for post-marketing surveillance of drug safety and effectiveness use two main approaches: common data models (CDMs) and common protocols. Networks such as the U.S.

The Effect of 12-Week e-Cigarette Use on Smoking Abstinence at 1 Year: The E3 Trial.

Background: The current evidence regarding the long-term efficacy of electronic cigarettes (e-cigarettes) for smoking cessation is unclear.

Objectives: The purpose of this study was to assess the efficacy, safety, and tolerability of nicotine and non-nicotine e-cigarettes for smoking cessation in the general population.

Methods: We randomized 376 adults who smoked ≥10 cigarettes/day and were motivated to quit at 17 Canadian sites to 12 weeks of nicotine (15 mg/mL) e-cigarettes (n = 128), non-nicotine e-cigarettes (n = 127), or no e-cigarettes (n = 121).

Target trial emulation of cardiovascular outcome trials of medications used to treat type 2 diabetes using real-world data: a systematic review of observational studies.

Background And Objectives: Cardiovascular outcome trials are mandated by the US Food and Drug Administration to assess the cardiovascular safety of new antidiabetic medications before entering the market. However, these trials often involve highly selective populations and results may not generalize to routine practice.

Methods: Our study aimed to synthesize observational studies to assess the generalizability of cardiovascular outcome trials to routine practice.

Temporal trends and clinical characteristics associated with pregnancy-related acute kidney injury in England: a population-based cohort study.

Background: Previous studies have reported an increase in pregnancy-related acute kidney injury, but the underlying reasons and patient characteristics associated with this trend are incompletely understood.

Objective: To describe temporal trends and identify clinical characteristics associated with pregnancy-related acute kidney injury in England.

Study Design: This population-based cohort study included all live birth and stillbirth pregnancies to persons aged 15 to 45 years, between 1998 and 2017, using general practitioner practices in England linked to hospitalization data.

Mechanisms of GLP-1 Receptor Agonist-Induced Weight Loss: A Review of Central and Peripheral Pathways in Appetite and Energy Regulation.

Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have become central in managing obesity and type 2 diabetes, primarily through appetite suppression and metabolic regulation. This review explores the mechanisms underlying GLP-1 RA-induced weight loss, focusing on central and peripheral pathways. Centrally, GLP-1 RAs modulate brain regions controlling appetite, influencing neurotransmitter and peptide release to regulate hunger and energy expenditure.

Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes : A Systematic Review of Randomized Controlled Trials.

Background: 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.

Purpose: To assess the efficacy and safety of GLP-1 RAs and co-agonists for the treatment of obesity among adults without diabetes.

Data Sources: MEDLINE, Embase, and Cochrane CENTRAL from inception to 4 October 2024.

Gestational diabetes mellitus and subsequent cardiovascular disease in a period of rising diagnoses: Cohort study.

Introduction: Evidence suggests that gestational diabetes mellitus (GDM) is associated with subsequent cardiovascular disease; however, it is unclear what impact changes in screening and diagnostic criteria have had on the association of GDM with long-term outcomes such as cardiovascular disease. The purpose of this study was to determine the association between GDM and subsequent cardiovascular disease during a period of rising gestational diabetes diagnosis in England. Specifically, associations were compared before and after 2008, when national guidelines supporting risk factor-based screening were introduced.

Metformin and risk of adverse pregnancy outcomes among pregnant women with gestational diabetes in the United Kingdom: A population-based cohort study.

Aims: Metformin is increasingly used off-label as the treatment of gestational diabetes (GDM). Our objective was to determine if metformin versus insulin initiation is associated with the adverse pregnancy outcomes.

Materials And Methods: We conducted a retrospective cohort study using data from the Clinical Practice Research Datalink, its pregnancy register, and Hospital Episode Statistics from 1998 to 2018.

e-Cigarettes, Smoking Cessation, and Weight Change: Retrospective Secondary Analysis of the Evaluating the Efficacy of e-Cigarette Use for Smoking Cessation Trial.

Background: While smoking cessation has been linked to substantial weight gain, the potential influence of e-cigarettes on weight changes among individuals who use these devices to quit smoking is not fully understood.

Objective: This study aims to reanalyze data from the Evaluating the Efficacy of e-Cigarette Use for Smoking Cessation (E3) trial to assess the causal effects of e-cigarette use on change in body weight.

Methods: This is a secondary analysis of the E3 trial in which participants were randomized into 3 groups: nicotine e-cigarettes plus counseling, nonnicotine e-cigarettes plus counseling, and counseling alone.

Comparative risk of infection of medications used for type 2 diabetes.

Introduction: Glucose-lowering drugs pose a potential infection risk among individuals with type 2 diabetes. The U.S.

A Meta-Analysis of 3-Year Outcomes of Drug-Coated Balloons Versus Drug-Eluting Stents for Small-Vessel Coronary Artery Disease.

Background: Drug-coated balloons (DCBs) may be a viable alternative to drug-eluting stents (DES) for de novo small caliber coronary artery lesions. However, there remains a lack of data regarding the long-term efficacy of this approach.

Objectives: The purpose of this study was to compare the rates of major adverse cardiovascular events (MACE) after 3-year follow-up among patients randomized to DCB versus DES for the treatment of small caliber coronary arteries with reference vessel diameter between 2 and 3 mm.

Levothyroxine Treatment of Subclinical Hypothyroidism and the Risk of Adverse Cardiovascular Events.

There is uncertainty as to whether treatment of subclinical hypothyroidism (SCH) is associated with cardiovascular outcomes. To determine whether levothyroxine replacement therapy decreases the risk of major adverse cardiovascular events (MACE) among individuals with SCH defined as having a thyrotropin (TSH) level between 5 and 10 mU/L. We conducted a population-based cohort study using a prevalent new-user design.

A systematic review and meta-analysis comparing outcomes between using subcutaneous insulin and continuous insulin infusion in managing adult patients with diabetic ketoacidosis.

Background: The purpose of this systematic review and meta-analysis was to synthesize the current literature to determine the safety and efficacy of using subcutaneous insulin compared to an intravenous (IV) insulin infusion in managing diabetic ketoacidosis (DKA).

Methods: We searched Ovid-Medline, EMBASE, SCOPUS, BIOSIS and CENTRAL from inception to April 26, 2024. Randomized controlled trials (RCTs) and observational studies that assessed the use of subcutaneous compared to intravenous insulin for the treatment of mild to moderate DKA were included.

Fluoroquinolones and the risk of severe hypoglycaemia among sulphonylurea users: Population-based cohort study.

Aim: Fluoroquinolone-related hypoglycaemia is rare but may become clinically relevant in individuals at high baseline hypoglycaemic risk, such as patients with diabetes using sulphonylureas. Our population-based cohort study assessed whether fluoroquinolones are associated with an increased risk of severe hypoglycaemia compared with amoxicillin among patients treated with sulphonylureas.

Materials And Methods: Using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data, we assembled a base cohort of patients who initiated second-generation sulphonylureas (1998-2020).

Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically important weight loss effects in patients with type 2 diabetes. However, its effects on sustained weight loss in patients without diabetes remains unclear. Our objective was to examine the long-term efficacy and safety of semaglutide use for weight loss in patients with overweight/obesity and without diabetes.

Effectiveness and safety of direct oral anticoagulants among patients with non-valvular atrial fibrillation and liver disease: A multinational cohort study.

Background And Aims: The effects of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) and liver disease remain poorly understood. Our multinational cohort study assessed the effectiveness and safety of DOACs in this high-risk population.

Methods: We assembled two population-based cohorts in United Kingdom and in Québec of NVAF patients with liver disease initiating DOACs or vitamin K antagonists (VKAs) between 2011 and 2020.

Standardizing to specific target populations in distributed networks and multisite pharmacoepidemiologic studies.

Distributed network studies and multisite studies assess drug safety and effectiveness in diverse populations by pooling information. Targeting groups of clinical or policy interest (including specific sites or site combinations) and applying weights based on effect measure modifiers (EMMs) prior to pooling estimates within multisite studies may increase interpretability and improve precision. We simulated a 4-site study, standardized each site using inverse odds weights (IOWs) to resemble the 3 smallest sites or the smallest site, estimated IOW-weighted risk differences (RDs), and combined estimates with inverse variance weights (IVWs).

Efficacy of interventions targeted at physician prescribers of opioids for chronic non-cancer pain: an overview of systematic reviews.

Background: To combat the opioid crisis, interventions targeting the opioid prescribing behaviour of physicians involved in the management of patients with chronic non-cancer pain (CNCP) have been introduced in clinical settings. An integrative synthesis of systematic review evidence is required to better understand the effects of these interventions. Our objective was to synthesize the systematic review evidence on the effect of interventions targeting the behaviours of physician opioid prescribers for CNCP among adults on patient and population health and prescriber behaviour.

Prescribing trends of proton pump inhibitors and histamine blockers among children in the United Kingdom (1998-2019): A population-based assessment.

Purpose: To describe the prescribing trends of proton pump inhibitors (PPIs) and H receptor antagonists (H RAs) among children with gastroesophageal reflux in the United Kingdom between 1998 and 2019.

Methods: We conducted a population-based retrospective cohort study using data from the Clinical Practice Research Datalink that included all children aged ≤18 years with a first ever diagnosis of gastroesophageal reflux between 1998 and 2019. Using negative binomial regression, we estimated crude and adjusted annual prescription rates per 1000 person-years and corresponding 95% confidence intervals (CIs) for PPIs and H RAs.