Daily Endocrinology Research Analysis
Three notable endocrinology-related studies shape diabetes care and cardiometabolic risk. A randomized trial found that universal midpregnancy screening for gestational diabetes (18–20 weeks) does not improve composite pregnancy outcomes versus standard 24–28 weeks, though neonatal hypoglycemia decreased. Comparative real-world analysis suggests semaglutide and liraglutide confer greater cardiovascular risk reduction among GLP-1 receptor agonists, and randomized GRADE data indicate fewer major E
Summary
Three notable endocrinology-related studies shape diabetes care and cardiometabolic risk. A randomized trial found that universal midpregnancy screening for gestational diabetes (18–20 weeks) does not improve composite pregnancy outcomes versus standard 24–28 weeks, though neonatal hypoglycemia decreased. Comparative real-world analysis suggests semaglutide and liraglutide confer greater cardiovascular risk reduction among GLP-1 receptor agonists, and randomized GRADE data indicate fewer major ECG abnormalities with liraglutide over 4 years.
Research Themes
- Optimal timing and strategy for gestational diabetes screening
- Comparative cardiovascular effectiveness of GLP-1 receptor agonists
- Cardiac electrical risk markers under glucose-lowering therapies
Selected Articles
1. The Effect of Midpregnancy Screening for Gestational Diabetes Mellitus on Pregnancy Outcomes: The TESGO Randomized Controlled Trial.
In this dual-center RCT, universal GDM screening at 18–20 weeks using a single 75-g OGTT did not improve the composite primary pregnancy outcome versus standard screening at 24–28 weeks; the trial was stopped early for futility. Neonatal hypoglycemia was significantly lower with midpregnancy screening, whereas neonatal adiposity among offspring of women with GDM diagnosed midpregnancy was higher. Adverse events were similar between groups.
Impact: A well-executed RCT addressing a timely clinical question shows that earlier universal GDM screening does not improve overall outcomes, informing guideline timing and resource allocation.
Clinical Implications: Maintain standard universal GDM screening at 24–28 weeks; consider targeted early screening only for high-risk women. Counsel that earlier detection may reduce neonatal hypoglycemia but could be associated with higher neonatal adiposity among those diagnosed early.
Key Findings
- The trial was stopped early for futility; the composite primary pregnancy outcome did not differ between 18–20-week universal screening and standard 24–28-week screening.
- Neonatal hypoglycemia was significantly lower in the midpregnancy screening group.
- Among women diagnosed with GDM via midpregnancy screening, neonatal adiposity was higher compared with standard screening.
- Adverse event rates were similar between groups.
Methodological Strengths
- Randomized, parallel-group design across two centers with intention-to-treat analysis.
- Uniform GDM diagnosis using 75-g OGTT and IADPSG criteria with a prespecified composite primary outcome.
Limitations
- Early stopping may have reduced power to detect modest differences.
- Conducted at two centers and limited to singleton pregnancies; generalizability may be constrained.
Future Directions: Evaluate risk-based early screening strategies, long-term metabolic outcomes in offspring, and reconcile neonatal adiposity findings with hypoglycemia benefits; assess cost-effectiveness across healthcare systems.
2. Comparative effectiveness of GLP-1 receptor agonists on cardiovascular outcomes among adults with type 2 diabetes and moderate cardiovascular risk: emulation of a target trial.
Using a target-trial emulation of over 80,000 adults with T2D at moderate cardiovascular risk, semaglutide and liraglutide were associated with lower MACE versus dulaglutide after IPTW adjustment. Semaglutide additionally reduced all-cause mortality, stroke, and revascularization; liraglutide reduced MACE and all-cause mortality. Findings inform GLP-1RA selection when prioritizing cardiovascular risk reduction.
Impact: Large-scale comparative effectiveness evidence across GLP-1RAs addresses a pressing clinical decision—agent selection for cardioprotection—using rigorous target-trial emulation methods.
Clinical Implications: When choosing a GLP-1RA for patients with T2D and moderate cardiovascular risk, semaglutide and liraglutide may be preferred for cardiovascular risk reduction. Decisions should incorporate patient-specific factors and acknowledge residual confounding inherent to claims-based studies.
Key Findings
- After IPTW, semaglutide vs dulaglutide was associated with lower risk of MACE (HR 0.85), expanded MACE (HR 0.92), all-cause mortality (HR 0.81), stroke (HR 0.82), and revascularization (HR 0.93).
- Liraglutide vs dulaglutide was associated with lower MACE (HR 0.84) and all-cause mortality (HR 0.79).
- Target-trial emulation with propensity score weighting enabled balanced comparison across >80,000 initiators.
Methodological Strengths
- Robust target-trial emulation with inverse probability of treatment weighting to address confounding.
- Large, contemporary comparative cohort spanning multiple GLP-1RAs and clinically meaningful endpoints.
Limitations
- Observational design with potential residual confounding and misclassification inherent to claims data.
- Medication dosing, adherence, and some clinical covariates may be incompletely captured; no randomized head-to-head comparisons.
Future Directions: Conduct head-to-head randomized trials among GLP-1RAs in moderate-risk populations; refine subgroup analyses (e.g., kidney function, age, prior CVD) and integrate comparative cost-effectiveness.
3. Differences in Prevalence and Incidence of Electrocardiogram Abnormalities and Cardiovascular Autonomic Neuropathy Among Randomized Glucose-Lowering Treatments in Early Type 2 Diabetes: The Glycemia Reduction Approaches in Diabetes (GRADE) Cohort.
In the randomized GRADE cohort with early T2D, ECG abnormalities and ECG-derived CAN were common at baseline. Over 4 years, the incidence of major ECG abnormalities was lower with liraglutide versus other therapies, while CAN incidence did not differ; one HRV measure was higher at year 2 with liraglutide. Findings suggest potential electrophysiologic cardioprotection with liraglutide.
Impact: Randomized head-to-head comparison across common glucose-lowering agents demonstrates fewer major ECG abnormalities with liraglutide over time, linking GLP-1RA therapy to potential arrhythmic risk modification.
Clinical Implications: When selecting add-on therapy to metformin in early T2D, liraglutide may offer advantages in reducing major ECG abnormalities; however, effects on CAN were not demonstrated. These data complement established cardiovascular benefits of GLP-1RAs.
Key Findings
- At baseline, 57.1% had ECG abnormalities and 52.8% had ECG-derived CAN; these were associated with older age and higher cardiovascular risk.
- At year 4, major ECG abnormalities were less frequent with liraglutide compared with non-liraglutide therapies (9% vs 13%; P=0.03).
- CAN incidence did not differ by treatment; SDNN (an HRV measure) was higher at year 2 with liraglutide (P=0.02).
Methodological Strengths
- Random assignment to four active glucose-lowering therapies with repeated standardized ECG assessments over 4 years.
- Adjusted repeated-measures logistic models accounting for baseline risk factors.
Limitations
- ECG outcomes were secondary and multiplicity may increase type I error; effect sizes were modest.
- Findings may not directly translate to hard clinical endpoints (e.g., arrhythmia, sudden death) without further study.
Future Directions: Prospective studies linking ECG changes under GLP-1RA therapy to arrhythmic events and cardiovascular outcomes; mechanistic studies on autonomic modulation; evaluation across other GLP-1RAs.