Daily Endocrinology Research Analysis
Analyzed 168 papers and selected 3 impactful papers.
Summary
Analyzed 168 papers and selected 3 impactful articles.
Selected Articles
1. Sitagliptin, Metformin and Glimepiride Fixed-Dose Combination Compared to Co-Administration of Metformin and High-Dose Glimepiride in Indian Patients With Type 2 Diabetes: A Randomised, Double-Blind, Double-Dummy, Phase 3 Clinical Study.
In a randomized, double-blind, double-dummy phase 3 trial in India (n=392), a triple fixed-dose combination of sitagliptin, metformin, and glimepiride achieved superior HbA1c reduction versus co-administered metformin plus high-dose glimepiride and was well tolerated. The trial was prospectively registered in the Indian registry.
Impact: This high-quality RCT supports a practical triple fixed-dose oral strategy that can enhance glycemic control and potentially adherence in settings with high pill burden.
Clinical Implications: Consider a triple FDC in patients with uncontrolled T2D on metformin to achieve greater HbA1c reduction while monitoring for sulfonylurea-related hypoglycemia. The approach may simplify regimens and improve adherence.
Key Findings
- A total of 392 adults with T2D were randomized: 190 to the sitagliptin+metformin+glimepiride FDC and 202 to metformin plus high-dose glimepiride.
- The triple FDC achieved superior HbA1c reduction versus the comparator regimen.
- Safety was acceptable and the regimen was well tolerated in this population.
Methodological Strengths
- Randomized, double-blind, double-dummy, phase 3 design with active comparator.
- Prospective trial registration (CTRI) and adequate sample size for efficacy assessment.
Limitations
- Exact HbA1c effect size and study duration are not specified in the abstract excerpt provided.
- Single-country population (India) may limit generalizability; inclusion of a sulfonylurea necessitates careful hypoglycemia monitoring.
Future Directions: Head-to-head comparisons versus SGLT2 inhibitors or GLP-1 receptor agonists and longer-term cardiovascular and renal outcomes are needed.
AIMS: This study assessed the efficacy and safety of a triple fixed-dose combination (FDC) of sitagliptin, metformin, and glimepiride versus co-administered metformin and glimepiride in Indian patients with uncontrolled Type 2 diabetes (T2D). MATERIALS AND METHODS: In this Phase 3, randomised, double-blind, double-dummy study, adult patients with T2D and glycated haemoglobin (HbA RESULTS: Overall, 190 patients were randomised to the SITA + MET + GLIM group and 202 to the Co-administration group. The least squares mean (standard error) change from baseline in HbA CONCLUSIONS: The triple FDC was superior to co-administered metformin and high-dose glimepiride for achieving glycaemic control and was well tolerated in Indian patients with T2D. TRIAL REGISTRATION: Clinical Trials Registry-India identifier: CTRI/2021/11/038169 (registered on 22 November 2021); URL: https://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NjI1Mjk=&Enc=&userName=.
2. Thyroid Function with Continuous KRT: A Prospective Study.
In a prospective ICU cohort, CKRT patients exhibited persistently lower fT4 and fT3 than matched controls, and both TSH and fT4 were measurable in CKRT effluent, confirming extracorporeal clearance. Most CKRT recipients developed severe, persistent non-thyroidal illness syndrome, and none achieved euthyroid status during therapy.
Impact: This is the first study to demonstrate direct clearance of TSH and free thyroxine by CKRT and link it to persistent NTIS, redefining interpretation of thyroid tests in critically ill patients on CKRT.
Clinical Implications: Thyroid tests in CKRT patients should be interpreted with caution; CKRT-mediated hormone and TSH clearance can exacerbate NTIS and mask true HPT-axis status. Routine thyroid hormone replacement should be avoided unless clear indications exist; priority should be given to treating underlying illness and reassessing after CKRT.
Key Findings
- Serum fT4 and fT3 were consistently lower in CKRT patients versus ICU controls across serial time points.
- TSH and fT4 were detectable in CKRT effluent, confirming extracorporeal clearance of thyroid-related analytes.
- Severe, persistent non-thyroidal illness syndrome predominated in the CKRT cohort; no patient became euthyroid during CKRT.
Methodological Strengths
- Prospective design with serial measurements in CKRT and matched ICU controls
- Direct effluent sampling demonstrating clearance of TSH and fT4; robust mixed-effects modeling with FDR correction
Limitations
- Single-center observational study limits generalizability
- Did not evaluate outcomes of thyroid hormone supplementation or long-term HPT-axis recovery post-CKRT
Future Directions: Multicenter studies should validate hormone clearance kinetics across CKRT modalities and membranes, define reference ranges for interpretation, and test targeted endocrine management strategies in CKRT-related NTIS.
BACKGROUND: AKI and ESKD requiring continuous kidney replacement therapy (CKRT) are associated with a high mortality rate. Solutes up to 40 kilodaltons (kDa) in size are amenable to CKRT clearance which includes thyroid stimulating hormone (TSH) (28 kDa), free thyroxine (fT4) (0.78 kDa), and free triiodothyronine (fT3) (0.68 kDa). The effect of CKRT on TSH and thyroid hormone clearance, thyroid function, and the hypothalamic-pituitary-thyroid (HPT) axis is unknown. METHODS: This prospective, single-center observational study enrolled 50 ICU patients requiring CKRT and 50 control ICU patients. Serum TSH, fT4, fT3, and reverse T3 (rT3) were measured prior to and on days 1, 3, 8, and 14 after CKRT initiation and at the same time points relative to enrollment in control patients; effluent TSH, fT4, and fT3 were measured on days 1, 3, 8, and 14. Thyroid function status was adjudicated on days 1, 3, 8, and 14. Statistical analyses included employment of linear mixed modelling and time-dependent adjustments, and ANOVA with FDR correction. RESULTS: Prior to and during CKRT, CKRT patients had lower fT4 and fT3 levels compared to controls, with a higher proportion of values below the normal reference range. TSH and fT4 were detected in the CKRT effluent, indicating clearance by CKRT. Severe and persistent non-thyroidal illness syndrome (NTIS) was seen in the CKRT cohort. No patient achieved euthyroid status while receiving CKRT. CONCLUSIONS: This is the first study to assess thyroid function and clearance of TSH and thyroid hormones during CKRT. We demonstrate that severe NTIS - characterized by low levels of fT4 and fT3 - occurs in the majority of CKRT patients. Furthermore, NTIS is persistent in patients receiving CKRT, which may be influenced by CKRT-mediated TSH and fT4 clearance. These novel complications may contribute to the high mortality rate observed in patients with either AKI or ESKD who receive CKRT.
3. Effect of an mHealth-assisted multifaceted lifestyle intervention on body-mass index, hepatic fat content and stiffness in children with overweight or obesity: a cluster randomised controlled trial.
In a six-school cluster randomized trial among 331 children aged 8–10 years with overweight/obesity, a multifaceted, mHealth-supported lifestyle program significantly reduced BMI and improved hepatic fat (CAP) and liver stiffness (LSM) versus usual care. A macroeconomic simulation suggested favorable long-term economic impact.
Impact: Provides randomized evidence that scalable, school-based and digitally supported interventions can simultaneously improve adiposity and liver health metrics in children, bridging endocrinology and hepatology.
Clinical Implications: Pediatric programs integrating school policies, nutritionist-led guidance, physical activity promotion, and mHealth support can be implemented to reduce BMI and improve MASLD-related parameters; objective elastography endpoints (CAP, LSM) are feasible outcomes for monitoring.
Key Findings
- Cluster randomized trial across six schools (n=331) showed significant reductions in BMI with the mHealth-assisted intervention versus control.
- Hepatic fat (CAP) and liver stiffness (LSM) improved significantly in the intervention group compared with controls.
- Macroeconomic modeling projected favorable long-term economic benefits of program implementation.
Methodological Strengths
- Cluster randomized controlled design with intention-to-treat analysis and mixed models accounting for clustering
- Objective liver endpoints via transient elastography (CAP, LSM) in addition to BMI
Limitations
- Only six clusters (schools), which may limit generalizability and statistical power for cluster-level heterogeneity
- Follow-up duration not detailed beyond primary endpoint window; long-term maintenance unknown
Future Directions: Scale-up trials with more clusters and longer follow-up should evaluate maintenance, cost-effectiveness in diverse settings, and integration with primary care to sustain MASLD risk reduction.
BACKGROUND: Lifestyle modification represents the cornerstone of the prevention and early management of obesity, hepatic fat content and stiffness in children. We aimed to evaluate the effectiveness of an mHealth-supported multifaceted lifestyle intervention on body-mass index (BMI), hepatic fat content and stiffness in children with overweight or obesity, and to estimate its potential long-term macroeconomic benefits. METHODS: In this cluster randomised controlled trial, six primary schools in Ningbo, China, were randomly assigned (1:1) to an intervention or control group. Children aged 8-10 years with overweight or obesity were enrolled. The intervention integrated school-based health education and polices, physical activity promotion, dietary guidance delivered by clinical nutritionists, and supportive mHealth components. Primary outcomes were changes in BMI, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM). Intention-to-treat analysis was performed using generalised linear mixed models accounting for school-level clustering and adjusting for baseline outcome values, age, and sex. A post-hoc macroeconomic simulation projected long-term economic effects. This trial is registered with ClinicalTrials.gov, NCT05482191. FINDINGS: From 6 to 30 September, 2022, 331 children (mean age 8.5 years [SD 0.3]; 36.3% girls) were enrolled. Compared with controls, the intervention group showed significant reductions in BMI (mean difference -0.38 kg/m INTERPRETATION: The mHealth-assisted lifestyle intervention significantly improved BMI, hepatic fat content and stiffness in children. The accompanying macroeconomic benefits support its integration into national public health and economic strategies. FUNDING: Major Science and Technology Projects for Health of Zhejiang Province; Cyrus Tang Foundation 2022.