Daily Endocrinology Research Analysis
Across endocrinology, a large meta-analysis clarifies the relative benefits and risks of anti-obesity medications, highlighting tirzepatide as top for weight loss and cardiometabolic improvements. A population-based study challenges routine albumin-adjustment of calcium, showing unadjusted total calcium aligns best with ionized calcium and reduces misclassification. A nationwide target trial emulation finds empagliflozin and dapagliflozin yield comparable long-term kidney outcomes in type 2 diab
Summary
Across endocrinology, a large meta-analysis clarifies the relative benefits and risks of anti-obesity medications, highlighting tirzepatide as top for weight loss and cardiometabolic improvements. A population-based study challenges routine albumin-adjustment of calcium, showing unadjusted total calcium aligns best with ionized calcium and reduces misclassification. A nationwide target trial emulation finds empagliflozin and dapagliflozin yield comparable long-term kidney outcomes in type 2 diabetes.
Research Themes
- Pharmacotherapy for obesity and cardiometabolic risk
- Laboratory diagnostics and calcium assessment
- Comparative effectiveness of SGLT2 inhibitors in diabetic kidney outcomes
Selected Articles
1. Safety and effects of anti-obesity medications on weight loss, cardiometabolic, and psychological outcomes in people living with overweight or obesity: a systematic review and meta-analysis.
Synthesizing 154 RCTs (n=112,515), this meta-analysis ranks anti-obesity medications: tirzepatide delivers the greatest weight loss and strong blood pressure/glucose reductions; semaglutide and liraglutide lower major adverse cardiovascular events. Naltrexone/bupropion may raise blood pressure, and phentermine/topiramate carries higher psychological adverse event risk.
Impact: Provides high-certainty comparative evidence across modern anti-obesity agents, informing drug selection beyond weight loss toward cardiometabolic and psychological profiles.
Clinical Implications: Prioritize tirzepatide for maximal weight loss and broad cardiometabolic benefit; consider semaglutide/liraglutide for MACE risk reduction. Monitor BP with naltrexone/bupropion and psychological side effects with phentermine/topiramate; tailor choices to comorbidities and tolerability.
Key Findings
- Among 154 RCTs (n=112,515), tirzepatide showed the greatest weight-loss effect (WMD -11.69 kg; 95% CI -19.22 to -4.15).
- Tirzepatide provided the strongest blood pressure and glucose-lowering benefits among agents evaluated.
- Semaglutide and liraglutide reduced major adverse cardiovascular events (MACEs).
- Naltrexone/bupropion was associated with increased blood pressure risk.
- Phentermine/topiramate had a higher risk of psychological adverse effects.
Methodological Strengths
- Comprehensive PRISMA-based search across major databases with PROSPERO registration
- Random-effects meta-analysis with GRADE assessment for certainty of evidence
- Large aggregate sample size (112,515) enabling robust comparative estimates
Limitations
- Heterogeneity across trials and populations may affect pooled estimates
- Reliance on summary-level data limits exploration of individual patient modifiers
Future Directions: Head-to-head RCTs and IPD meta-analyses to refine comparative effectiveness and safety by patient subgroups and comorbidities; longer-term outcomes (maintenance, MACE, renal) and real-world adherence studies.
2. Use of Albumin-Adjusted Calcium Measurements in Clinical Practice.
In 22,658 adults with simultaneous testing, unadjusted total calcium correlated better with ionized calcium than common albumin-adjustment formulas and yielded the highest agreement in classifying hypo-, normo-, or hypercalcemia. Adjustment formulas increased misclassification, especially with hypoalbuminemia.
Impact: Challenges entrenched laboratory practice by showing albumin-adjustment offers no advantage and may worsen classification, prompting a shift toward unadjusted total calcium or direct ionized calcium.
Clinical Implications: Prefer unadjusted total calcium for routine assessment and avoid automatic albumin-adjustment, particularly in hypoalbuminemia. When clinical stakes are high or results discordant, measure ionized calcium directly.
Key Findings
- Unadjusted total calcium showed higher correlation with ionized calcium (R2=71.7%) than the simplified Payne formula (R2=68.9%).
- Overall classification agreement with ionized calcium was best for unadjusted total calcium (74.5%) versus Payne formulas (63.0% and 58.7%).
- Albumin-adjustment formulas performed worse in hypoalbuminemia (albumin <30 g/L), increasing misclassification risk.
Methodological Strengths
- Large, population-based cohort with 22,658 simultaneous total and ionized calcium measurements
- Compared 10 adjustment formulas with ionized calcium reference and assessed clinical classification agreement
Limitations
- Cross-sectional observational design limits causal inference
- Single-province health system may limit generalizability
Future Directions: Prospective validation across diverse settings and exploration of decision-support rules for when to obtain ionized calcium versus relying on unadjusted total calcium.
3. Effectiveness of Empagliflozin vs Dapagliflozin for Kidney Outcomes in Type 2 Diabetes.
In a nationwide target trial emulation (n=50,283), empagliflozin and dapagliflozin produced comparable 6-year risks of acute kidney injury, incident CKD (G3–G5 or A2/A3), and CKD progression, with balanced covariates after weighting and consistent per-protocol results.
Impact: Offers high-quality real-world comparative effectiveness evidence where no head-to-head RCT exists, guiding SGLT2 inhibitor selection for renal protection in type 2 diabetes.
Clinical Implications: Empagliflozin and dapagliflozin can be considered interchangeable for long-term kidney outcomes; selection may be based on patient-specific factors (CV history, tolerability, cost/access) and extra-renal evidence.
Key Findings
- After weighting 56 confounders, covariates were well balanced between empagliflozin (n=32,819) and dapagliflozin (n=17,464) initiators.
- Six-year risks were comparable for acute kidney injury (18.2% vs 18.5%; RR 0.98, 95% CI 0.91-1.06) and incident CKD stages G3–G5 (11.8% vs 12.1%; RR 0.97, 95% CI 0.89-1.05).
- Albuminuria (A2/A3) incidence (14.8% vs 14.3%; RR 1.04, 95% CI 0.93-1.15) and CKD progression (≥40% eGFR decline: 5.3% vs 5.7%; RR 0.94, 95% CI 0.56-1.58) were also similar.
- Per-protocol analyses corroborated intention-to-treat results.
Methodological Strengths
- Target trial emulation with nationwide, routinely collected data and competing risk methods (Aalen-Johansen)
- Extensive confounder adjustment (56 variables) with weighting achieving good covariate balance
Limitations
- Observational emulation cannot fully eliminate residual confounding and channeling bias
- Findings from a Danish healthcare setting may limit generalizability to other systems
Future Directions: Head-to-head randomized trials or advanced emulations incorporating additional outcomes (e.g., cardiovascular events) and subgroup analyses by baseline CKD and albuminuria.