Proteomic pathways across the ejection fraction spectrum in patients with heart failure and diabetes mellitus: an EXSCEL trial substudy.

Ejection fraction (EF) is a key component of heart failure (HF) classification. However, the biologic basis of HF with mildly reduced EF (HFmrEF) as a distinct biologic entity distinct from HF with preserved EF (HFpEF) and reduced EF (HFrEF) has not been well characterized. The EXSCEL trial randomized participants with type 2 diabetes (T2DM) to a once-weekly glucagon-like peptide receptor agonist (GLP-1 RA) exenatide (EQW) vs.

Accuracy of Dexcom G6 Pro Continuous Glucose Monitor in the Intensive Care Setting: TIGHT ICU G6 Study.

To evaluate the accuracy of the Dexcom G6 Pro continuous glucose monitoring (CGM) system in the intensive care unit (ICU) setting. We performed a prospective, observational, multicenter study in adult ICU patients with a known diagnosis of diabetes or stress hyperglycemia who were being treated with insulin. Two Dexcom G6 Pro sensors were placed.

Glucagon-like Peptide-1 Receptor Agonists in Asthma Exacerbations: An Application of High-Dimensional Iterative Causal Forest to Identify Subgroups.

Background: Glucagon-like Peptide-1 Receptor Agonists (GLP1RA) may reduce asthma exacerbation (AE) risk, but it is unclear which populations benefit most. Recent pharmacoepidemiologic studies have employed iterative causal forest (iCF), a machine learning (ML) algorithm, to identify subgroups with heterogeneous treatment effects (HTEs). While iCF does not rely on prior knowledge of treatment-variable interactions, it may be constrained by missing or poorly defined variables in pharmacoepidemiologic studies.

High-dimensional Iterative Causal Forest (hdiCF) for Subgroup Identification Using Health Care Claims Data.

We tested a novel high-dimensional approach (using 1 ordinal variable per code with up to four levels: zero, occurred once, sporadically, or frequent) against the standard high-dimensional propensity score (hdPS) method (up to 3 binary variables per code) for detecting heterogeneous treatment effects (HTE). Using the iterative causal forest (iCF) subgrouping algorithm, we analyzed a new-user cohort of 8,075 sodium-glucose cotransporter-2 inhibitors and 7,313 glucagon-like peptide-1 receptor agonists from a 20% random Medicare sample (2015-2019) with ≥1-year parts A/B/D enrollment and without severe renal disease. We extracted the top 200 prevalent codes across diagnoses, procedures, and prescriptions during the 1-year baseline.

Association of Hospitalizations With Randomized Glycemia-Lowering Treatment in GRADE.

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.

Time to Treatment Intensification with Glucagon-Like Peptide-1 Receptor Agonists Versus Comparators in People with Type 2 Diabetes Treated with Metformin.

Introduction: Treatment intensification is often required to attain glycemic targets in people living with type 2 diabetes (T2D) but can introduce regimen complexity and increase medication burden. Whether rates of treatment intensification differ by glucose-lowering medication class is unclear. This study investigated comparative treatment durability of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus standard T2D treatments, with implications for longitudinal risk mitigation and the need for treatment intensification.

Dexcom G7 Accuracy and Reproducibility in the Intensive Care Unit.

To evaluate the accuracy of Dexcom G7 continuous glucose monitor (CGM) in the intensive care unit (ICU) setting. We performed a prospective, single-center study in patients with known diagnosis of diabetes or stress hyperglycemia and treated with insulin. Two Dexcom G7 sensors were placed on the abdomen and/or upper arm.

High-Dose Semaglutide (Up to 16 mg) in People With Type 2 Diabetes and Overweight or Obesity: A Randomized, Placebo-Controlled, Phase 2 Trial.

Objective: Studies have demonstrated dose-dependent efficacy of glucagon-like peptide 1 receptor agonists for glycemic control and body weight. The aim of this trial was to characterize the dose-dependent effects of semaglutide (up to 16 mg/week) in people with type 2 diabetes and overweight or obesity.

Research Design And Methods: In this parallel-group, participant- and investigator-blinded, phase 2 trial, 245 individuals with type 2 diabetes and BMI ≥27 kg/m2 on metformin were randomized to weekly semaglutide (2, 8, or 16 mg s.

Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes.

Background: The cardiovascular safety of oral semaglutide, a glucagon-like peptide 1 receptor agonist, has been established in persons with type 2 diabetes and high cardiovascular risk. An assessment of the cardiovascular efficacy of oral semaglutide in persons with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both is needed.

Methods: In this double-blind, placebo-controlled, event-driven, superiority trial, we randomly assigned participants who were 50 years of age or older, had type 2 diabetes with a glycated hemoglobin level of 6.

Cardiovascular and Kidney Outcomes and Mortality With Long-Acting Injectable and Oral Glucagon-Like Peptide 1 Receptor Agonists in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Trials.

Background: Glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce the incidence of major adverse cardiovascular events (MACE) in type 2 diabetes (T2D), although whether benefits extend to both subcutaneous and oral formulations remains unclear.

Purpose: In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinetics sufficient to provide 24-h activity) GLP-1RA in T2D.

Data Sources: A systematic review of PubMed was conducted (to 7 February 2025).

Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial.

Background: Both GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter-2) inhibitors (SGLT2i) improve cardiovascular outcomes in people with type 2 diabetes and cardiovascular or chronic kidney disease. However, there are limited data about the effect of combining these agents on cardiovascular and safety outcomes.

Methods: The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo.

Caution in Handling Switchers in Pharmacoepidemiologic Studies Estimating Treatment Effects: The Example of Dipeptidyl Peptidase-4 Inhibitors and Inflammatory Bowel Disease.

Real-world evidence assessing dipeptidyl peptidase-4 inhibitors (DPP4i)'s risk of inflammatory bowel disease (IBD) is conflicting. One study modelling DPP4i as a time varying exposure (TVE) observed a harmful effect in a UK population, while an active-comparator new-user (ACNU) study observed a null effect in a US population. To assess the impact of study design in estimating treatment effect, we implemented both designs in the UK Clinical Practice Research Datalink population from 2007-2022.

A bioinspired polymeric membrane-enclosed insulin crystal achieves long-term, self-regulated drug release for type 1 diabetes therapy.

The nuclear envelope serves as a highly regulated gateway for macromolecule exchange between the nucleus and cytoplasm in eukaryotes. Here we have developed a cell nucleus-mimicking polymeric membrane-enclosed system for long and self-regulated therapy. A polymeric nano-membrane with nanopores is conformally synthesized in situ on the surface of each insulin crystal, ensuring sustained, adjustable and zero-order drug release kinetics.

Automated Insulin Delivery in Adults With Type 2 Diabetes: A Nonrandomized Clinical Trial.

Importance: There is a need for additional treatment options for people with type 2 diabetes treated with insulin. Given the limited data on the use of automated insulin delivery (AID) systems in type 2 diabetes, studies evaluating their safety and efficacy are important.

Objective: To evaluate the association of AID with hemoglobin A1c (HbA1c) levels in a diverse cohort of adults with type 2 diabetes.

A Randomized Trial Comparing Inhaled Insulin Plus Basal Insulin Versus Usual Care in Adults With Type 1 Diabetes.

Objective: To evaluate a regimen of inhaled Technosphere insulin (TI) plus insulin degludec in adults with type 1 diabetes, who prestudy were predominately using either an automated insulin delivery (AID) system or multiple daily insulin injections (MDI) with continuous glucose monitoring.

Research Design And Methods: At 19 sites, adults with type 1 diabetes were randomly assigned to TI plus insulin degludec (N = 62) or usual care (UC) with continuation of prestudy insulin delivery method (N = 61) for 17 weeks.

Results: Prestudy, AID was used by 48% and MDI by 45%.

Results From a Randomized Trial of Intensive Glucose Management Using CGM Versus Usual Care in Hospitalized Adults With Type 2 Diabetes: The TIGHT Study.

Objective: To evaluate whether continuous glucose monitoring (CGM) could assist providers in intensifying glycemic management in hospitalized patients with type 2 diabetes.

Research Design And Methods: At six academic hospitals, adults with type 2 diabetes hospitalized in a non-intensive care setting were randomly assigned to either standard therapy with glucose target 140-180 mg/dL (standard group) or intensive therapy with glucose target 90-130 mg/dL guided by CGM (intensive group). The primary outcome was mean glucose measured with CGM (blinded in standard group), and the key secondary outcome was CGM glucose <54 mg/dL.

A genome-wide association study identifies genetic determinants of hemoglobin glycation index with implications across sex and ethnicity.

Introduction: We investigated the genetic determinants of variation in the hemoglobin glycation index (HGI), an emerging biomarker for the risk of diabetes complications.

Methods: We conducted a genome-wide association study (GWAS) for HGI in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial ( = 7,913) using linear regression and additive genotype encoding on variants with minor allele frequency greater than 3%. We conducted replication analyses of top findings in the Atherosclerosis Risk in Communities (ARIC) study with inverse variance-weighted meta-analysis.