Publications by authors named "Deborah J Wexler"

Importance: Type 2 diabetes involves progressive loss of insulin secretion from pancreatic β cells in the setting of insulin resistance and manifests clinically as hyperglycemia. Type 2 diabetes accounts for 90% to 95% of all cases of diabetes globally, with estimates ranging from 589 million to 828 million people worldwide. In the US, type 2 diabetes affects approximately 1 in 6 adults.

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Rationale & Objective: Tirzepatide, a dual GIP/GLP-1 receptor agonist, has been approved for type 2 diabetes (T2D) and obesity. However, the real-world utilization of tirzepatide remains unexplored, particularly in patients with chronic kidney disease (CKD), where the prevalence of T2D and obesity is high. This study aimed to describe the utilization trends of tirzepatide, glucose-lowering medications (GLMs), and anti-obesity medications (AOMs) in patients with CKD, with and without T2D.

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Objective: To assess time trends of and examine which sociodemographic and clinical characteristics are associated with continuous glucose monitoring (CGM) initiation in insulin-treated older adults with type 2 diabetes (T2D).

Research Design And Methods: Using data from Medicare Fee-for-Service (2013-2020) and Optum's deidentified Clinformatics Data Mart Database (Clinformatics) (2013-2022), we identified patients aged ≥65 years with T2D receiving insulin therapy who initiated CGM annually. Initiation of a CGM device was defined based on Current Procedural Terminology codes and National Drug Codes.

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Objective: To compare rates of and risk factors for hospitalizations among Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) participants taking metformin and randomly assigned to insulin glargine U-100, glimepiride, liraglutide, or sitagliptin.

Research Design And Methods: Intention-to-treat (ITT) (N = 5,047) and on-assigned-treatment (AT) (N = 4,830) data sets were used. Baseline differences between those hospitalized versus those not hospitalized were assessed.

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Objective: Weight gain with glucose-lowering medications may interfere with effective type 2 diabetes (T2D) management. We evaluated weight change and the effect of weight gain on outcomes over 5 years on four diabetes medications.

Research Design And Methods: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D.

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Background: Recent trends in use of tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonist (RA), versus other glucose-lowering medications (GLMs) and weight-lowering medications (WLMs) remain unexplored.

Objective: To describe trends in insurance claims for GLMs and WLMs after tirzepatide approval.

Design: Population-based cohort study.

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Importance: Recent studies have suggested that sodium-glucose cotransporter-2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase 4 inhibitors (DPP-4is) may benefit patients with chronic obstructive pulmonary disease (COPD). However, clinical evidence is lacking on their comparative association with COPD exacerbations in US patients with type 2 diabetes (T2D).

Objective: To compare the risk of moderate or severe COPD exacerbations among SGLT-2is, GLP-1RAs, and DPP-4is.

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To date, there are limited studies describing the use of glucose-lowering medications (GLMs) in adult kidney transplant recipients (KTRs), and the uptake of sodium glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1RAs). Thus, we aimed to evaluate the use of GLMs, including SGLT2i and GLP1RA, among adult KTRs with type 2 diabetes (T2D). This is an ecologic study of adult KTR with T2D.

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Importance: Evidence on cardiovascular benefits and safety of sodium-glucose cotransporter 2 (SGLT-2) inhibitors is mainly from placebo-controlled trials. Therefore, the comparative effectiveness and safety of individual SGLT-2 inhibitors remain unknown.

Objective: To compare the use of canagliflozin or dapagliflozin with empagliflozin for a composite outcome (myocardial infarction [MI] or stroke), heart failure hospitalization, MI, stroke, all-cause death, and safety outcomes, including diabetic ketoacidosis (DKA), lower-limb amputation, bone fracture, severe urinary tract infection (UTI), and genital infection and whether effects differed by dosage or cardiovascular disease (CVD) history.

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Background: The prevalence, chronicity and clinical impact of type 2 diabetes (T2D) defines this disease state as a critical determinant in morbidity and mortality, as encountered by individuals, health care systems, and public health in general. The need to understand and optimize T2D identification and management is now further heightened by the advent of medications with established cardiovascular (CV) and kidney benefits in such patients, namely sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA). Prescription rates for these agents have remained low despite guidelines incorporating and emphasizing their use.

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Article Synopsis
  • Empagliflozin may reduce the risk of diabetic retinopathy (DR) by preventing the loss of retinal pericytes, but its effectiveness compared to DPP4 inhibitors in patients with type 2 diabetes (T2D) is not well established.
  • A study was conducted using U.S. insurance claims data from 2014 to 2019, focusing on adults with T2D who were newly prescribed either empagliflozin or a DPP4 inhibitor, and looking at the incidence of nonproliferative DR and its progression.
  • Results showed that among matched patient pairs, empagliflozin's impact on the rates of incident DR and progression was analyzed, with significant data collected over an average
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Objective: To emulate target trials comparing recurrence of nephrolithiasis among patients with pre-existing nephrolithiasis (overall and stratified by concomitant gout) initiating sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus an active comparator.

Design: Target trial emulation studies.

Setting: Canadian population database, January 2014 to June 2022.

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Objective: To assess whether use of glucagon-like peptide-1 (GLP-1) receptor agonists before upper gastrointestinal endoscopy is associated with increased risk of pulmonary aspiration or discontinuation of the procedure compared with sodium-glucose cotransporter-2 (SGLT-2) inhibitors.

Design: Cohort study.

Setting: Two deidentified US commercial healthcare databases.

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Article Synopsis
  • Non-randomized studies suggest bariatric surgery may significantly reduce mortality within 6-12 months compared to non-surgical patients, but these results might be influenced by biases.
  • A review of 21 relevant studies revealed that many suffered from immortal time bias and confounding bias related to body mass index (BMI), affecting the reliability of their findings.
  • The analysis suggests that adjusting for these biases led to less extreme conclusions about the effectiveness of bariatric surgery, emphasizing the need for better study designs in future research.
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Objectives: To evaluate the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors in preventing hyperkalemia in people with type 2 diabetes in routine clinical practice.

Design: Population based cohort study with active-comparator, new user design.

Setting: Claims data from Medicare and two large commercial insurance databases in the United States from April 2013 to April 2022.

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Objective: We compared health care resource utilization (HCRU) and costs for inpatient and outpatient services and dispensed medications in older adults with type 2 diabetes initiating empagliflozin versus dipeptidyl peptidase 4 inhibitors (DPP-4is).

Research Design And Methods: The study population included U.S.

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Background: Hyperuricemia is frequently observed in patients with type 2 diabetes (T2D) and is associated with increased risk of gout and cardiovascular disease (CVD). Empagliflozin lowers serum urate levels by enhancing its urinary excretion.

Objective: To compare initiators of empagliflozin vs dipeptidyl peptidase-4 inhibitor (DPP4i) and initiators of empagliflozin vs glucagon-like peptide-1 receptor agonist (GLP-1RA) with respect to the risk of incident gout events.

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Importance: Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are a revolutionary treatment for type 2 diabetes (T2D) with cardiovascular, kidney, and serum urate-lowering benefits.

Objective: To compare risk of incident gout and rate of recurrent flares between patients with T2D initiating SGLT2i vs sulfonylurea, most common second-line glucose-lowering therapy, when added to metformin monotherapy.

Design, Setting, And Participants: This sequential, propensity score-matched, new-user comparative effectiveness study using target trial emulation framework included adults with T2D receiving metformin monotherapy in a Canadian general population database from January 1, 2014, to June 30, 2022.

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Background: Several SGLT2i (sodium-glucose transport protein 2 inhibitors) and GLP1-RA (glucagon-like peptide-1 receptor agonists) reduce cardiovascular events and improve kidney outcomes in patients with type 2 diabetes; however, utilization remains low despite guideline recommendations.

Methods: A randomized, remote implementation trial in the Mass General Brigham network enrolled patients with type 2 diabetes with increased cardiovascular or kidney risk. Patients eligible for, but not prescribed, SGLT2i or GLP1-RA were randomly assigned to simultaneous virtual patient education with concurrent prescription of SGLT2i or GLP1-RA (ie, Simultaneous) or 2 months of virtual education followed by medication prescription (ie, Education-First) delivered by a multidisciplinary team driven by nonlicensed navigators and clinical pharmacists who prescribed SGLT2i or GLP1-RA using a standardized treatment algorithm.

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Aims/hypothesis: Limited evidence exists on the comparative safety and effectiveness of empagliflozin against alternative glucose-lowering medications in individuals with type 2 diabetes with the broad spectrum of cardiovascular risk. The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) cohort study was designed to monitor the safety and effectiveness of empagliflozin periodically for a period of 5 years with data collection from electronic healthcare databases.

Methods: We identified individuals ≥18 years old with type 2 diabetes who initiated empagliflozin or dipeptidyl peptidase-4 inhibitors (DPP-4i) from 2014 to 2019 using US Medicare and commercial claims databases.

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Article Synopsis
  • * The combination of gout and its related conditions leads to higher rates of early death, regardless of typical risk factors like urate levels.
  • * SGLT2 inhibitors are promising treatments for gout as they reduce both gout symptoms and associated health risks, while also lowering urate levels and the chances of heart failure and kidney disease.
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Purpose: The purpose of the study was to explore the thoughts, feelings, motivations, and assignment preferences of community health center patients with type 2 diabetes considering participation in a 2-year lifestyle intervention trial aimed at weight loss and increased physical activity. The reasons for patients' delivery mode preferences were also explored to aid in the design of future interventions for controlled trials.

Methods: Using structured telephone interview guides, 57 patients with type 2 diabetes receiving primary care at 3 community health centers affiliated with an academic medical center were interviewed regarding the perceived pros and cons of each of the 3 possible treatment assignments: telephone conference group, in-person group, or individual medical nutrition therapy.

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