Daily Endocrinology Research Analysis
A 16-week randomized controlled trial shows time-restricted eating (TRE) reduces hepatic steatosis in MASLD comparably to calorie restriction with good tolerability. A phase 3 randomized trial in Chinese statin-intolerant patients demonstrates the PCSK9 monoclonal antibody ongericimab reduces LDL-C by ~66% with a safety profile similar to placebo. A longitudinal cohort of ~196,000 Japanese adults validates composite obesity–lipid indices (AIP, CMI, LAP) as strong predictors of incident type 2 di
Summary
A 16-week randomized controlled trial shows time-restricted eating (TRE) reduces hepatic steatosis in MASLD comparably to calorie restriction with good tolerability. A phase 3 randomized trial in Chinese statin-intolerant patients demonstrates the PCSK9 monoclonal antibody ongericimab reduces LDL-C by ~66% with a safety profile similar to placebo. A longitudinal cohort of ~196,000 Japanese adults validates composite obesity–lipid indices (AIP, CMI, LAP) as strong predictors of incident type 2 diabetes.
Research Themes
- Lifestyle interventions for metabolic liver disease
- Lipid-lowering biologics in statin-intolerant patients
- Risk prediction for incident type 2 diabetes using composite obesity–lipid indices
Selected Articles
1. Efficacy and safety of time-restricted eating in metabolic dysfunction-associated steatotic liver disease.
In a 16-week three-arm RCT (n=333), TRE reduced hepatic steatosis by 25.8% versus 0.7% with standard care (p<0.001), achieving similar reductions as calorie restriction (−24.7%; p>0.999). TRE also led to greater reductions in body weight, waist circumference, and fat mass than standard care, with no differences versus calorie restriction, and no serious adverse events.
Impact: Provides randomized evidence that TRE is as effective as calorie restriction for reducing liver fat in MASLD, offering a pragmatic dietary strategy with good safety.
Clinical Implications: TRE can be considered as an alternative to calorie restriction for short-term reduction of hepatic steatosis in MASLD, with similar metabolic benefits and acceptable safety. Long-term adherence and histological outcomes remain to be established.
Key Findings
- TRE reduced hepatic steatosis by −25.8% vs standard of care 0.7% (p<0.001).
- TRE achieved similar hepatic fat reduction as calorie restriction (−24.7%; p>0.999).
- TRE led to greater reductions in body weight, waist circumference, and fat mass versus standard care.
- Liver stiffness, glucose homeostasis, and sleep quality changes were comparable between TRE and calorie restriction.
- No serious adverse events were reported.
Methodological Strengths
- Randomized, three-arm design with active comparator (calorie restriction) and MRI-PDFF primary endpoint.
- Adequate sample size (n=333) with pre-registration and safety monitoring; full analysis set used.
Limitations
- Short intervention duration (16 weeks) without histological confirmation.
- Open-label dietary interventions may introduce performance bias; generalizability beyond study population uncertain.
Future Directions: Assess long-term adherence, histological endpoints, and cardiometabolic outcomes; evaluate TRE in diverse MASLD phenotypes and in combination with pharmacotherapies.
2. Efficacy and safety of ongericimab in Chinese statin-intolerant patients with primary hypercholesterolemia or mixed dyslipidemia: a randomized, placebo-controlled phase 3 trial.
In 139 statin-intolerant Chinese adults, ongericimab reduced LDL-C by an LS mean 66.2% versus placebo at week 12 (p<0.0001), with sustained reductions through week 52. Non-HDL-C, ApoB, total cholesterol, and Lp(a) also decreased significantly, and overall adverse event rates were comparable to placebo.
Impact: Delivers rigorous, population-specific phase 3 evidence for a novel PCSK9 mAb in statin-intolerant patients, addressing an important therapeutic gap.
Clinical Implications: Ongericimab is a potent LDL-lowering option for statin-intolerant patients; clinicians may consider it when LDL-C goals are unmet with non-statin therapies. Outcome trials are needed to confirm cardiovascular benefit.
Key Findings
- LDL-C LS mean reduction vs placebo at week 12: −66.2% (95% CI −74.2% to −58.2%; p<0.0001).
- Reductions in non-HDL-C, ApoB, total cholesterol, and Lp(a) were significant.
- LDL-C reductions were sustained through week 52 in the open-label period.
- Overall incidence of treatment-emergent adverse events was comparable between groups.
Methodological Strengths
- Randomized, multicenter, double-blind, placebo-controlled phase 3 design.
- Prespecified lipid endpoints with sustained follow-up to 52 weeks.
Limitations
- Double-blind period was 12 weeks; cardiovascular outcomes were not assessed.
- Population limited to Chinese statin-intolerant patients; generalizability may be restricted.
Future Directions: Conduct cardiovascular outcomes trials, comparative effectiveness studies vs other PCSK9 inhibitors or inclisiran, and long-term safety/cost-effectiveness assessments.
3. Predictive value of obesity-related indices for incident type 2 diabetes mellitus: a longitudinal study of the Fukushima Health Database 2015-2021.
Among 195,989 Japanese adults followed a mean 4.61 years, higher quartiles of obesity–lipid indices were associated with 1.33–4.22-fold higher T2DM risk. AIP, CMI, and LAP showed the best discrimination (AUC 0.821–0.844), outperforming Mets-IR and TyG; predictive performance was stronger in participants <50 years and those with BMI <25 kg/m2.
Impact: Offers robust, population-scale validation of practical indices (AIP/CMI/LAP) for incident T2DM prediction, supporting risk stratification beyond BMI in East Asian adults.
Clinical Implications: Integrating AIP, CMI, or LAP into screening could identify high-risk individuals, particularly younger or non-obese adults, enabling earlier preventive interventions.
Key Findings
- In multivariable models, highest quartiles of indices conferred 1.33–4.22-fold higher T2DM risk vs lowest quartiles.
- AIP, CMI, and LAP achieved AUCs of 0.821–0.844, outperforming Mets-IR and TyG (0.756–0.780).
- Risk gradients were more pronounced in participants <50 years in both sexes.
- Predictive performance was higher among participants with BMI <25 kg/m2.
Methodological Strengths
- Very large longitudinal cohort (n=195,989) with mean 4.61-year follow-up.
- Multivariable Cox regression, sex- and age-stratified analyses, and ROC comparisons across indices.
Limitations
- Retrospective observational design with potential residual confounding and misclassification.
- External validation and clinical impact of index-guided interventions were not assessed.
Future Directions: Prospective validation, integration into clinical risk calculators, threshold optimization, and randomized trials of index-guided prevention strategies.