Daily Endocrinology Research Analysis
A multicentre randomized trial in Lancet found that single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) leads to superior 2-year weight loss versus Roux-en-Y gastric bypass with comparable safety. A meta-analysis of 98 RCTs plus FAERS pharmacovigilance confirms SGLT-2 inhibitors markedly raise genital mycotic infection risk, while UTI signals are inconsistent. A large UK Biobank cohort shows central obesity (waist-to-height ratio) independently predicts incident glenohumeral
Summary
A multicentre randomized trial in Lancet found that single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) leads to superior 2-year weight loss versus Roux-en-Y gastric bypass with comparable safety. A meta-analysis of 98 RCTs plus FAERS pharmacovigilance confirms SGLT-2 inhibitors markedly raise genital mycotic infection risk, while UTI signals are inconsistent. A large UK Biobank cohort shows central obesity (waist-to-height ratio) independently predicts incident glenohumeral osteoarthritis beyond BMI.
Research Themes
- Comparative effectiveness in metabolic/bariatric surgery
- Drug safety and infectious adverse events with SGLT-2 inhibitors
- Central obesity metrics (WHtR) and musculoskeletal risk
Selected Articles
1. Efficacy and safety of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy versus Roux-en-Y gastric bypass in France (SADISLEEVE): results of a randomised, open-label, superiority trial at 2 years of follow-up.
In a French multicentre, open-label RCT (n=381), SADI-S achieved superior weight loss versus RYGB at 2 years with a comparable safety profile. The trial used intention-to-treat analysis and recruited across 22 bariatric centers.
Impact: This is the first large randomized comparison suggesting SADI-S may outperform the current standard RYGB with similar safety at 2 years, informing surgical decision-making in severe obesity.
Clinical Implications: SADI-S may be considered preferentially for selected patients seeking greater weight loss, with similar short- to mid-term safety to RYGB. Long-term nutritional monitoring remains critical when adopting more malabsorptive procedures.
Key Findings
- Across 22 French bariatric centers, 381 patients were randomized (SADI-S 190; RYGB 191) with intention-to-treat analysis.
- SADI-S produced superior weight loss at 2 years compared with RYGB.
- Safety profiles were similar between groups over 2 years.
Methodological Strengths
- Multicentre randomized superiority design with intention-to-treat analysis
- Direct head-to-head comparison of two widely used bariatric procedures over 2 years
Limitations
- Open-label design may introduce performance or detection bias
- Only 2-year follow-up; long-term efficacy, nutritional deficiencies, and metabolic outcomes remain to be established
Future Directions: Assess 5–10 year outcomes including diabetes remission, micronutrient deficiencies, bone health, quality of life, and cost-effectiveness; define optimal limb lengths and nutritional protocols for SADI-S.
BACKGROUND: Since 2007, single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) has been proposed as an alternative to Roux-en-Y gastric bypass (RYGB) in the treatment of obesity. We conducted a multicentre randomised trial, with the hypothesis that SADI-S could be more effective than RYGB at 2-year follow-up. METHODS: This multicentre, open-label, individually randomised superiority trial was conducted in France; patients were recruited from 22 bariatric institutions, mostly public academic hospitals. Key inclusion criteria were patients with a BMI ≥40 kg/m FINDINGS: Between Nov 8, 2018, and Sept 29, 2021, a total of 381 patients were randomly assigned (intention-to-treat population) and included in the primary analysis (SADI-S: 190, RYGB: 191). Mean age was 44·4 years (SD 10·64), mean BMI was 46·2 kg/m INTERPRETATION: SADI-S showed superior weight loss compared with RYGB at 2 years, with a similar safety profile. FUNDING: French Ministry of Health (Direction Générale de l'offre de Soin - DGOS).
2. Risk of genitourinary tract infections with SGLT-2 inhibitors in type 2 diabetes mellitus: A meta-analysis of randomised controlled trials and disproportionality analysis using FAERS.
Across 98 RCTs (n=91,756), SGLT-2 inhibitors tripled to quadrupled the risk of genital mycotic infections versus placebo or active comparators, with heterogeneity by drug, sex, and duration. FAERS disproportionality analyses corroborated signals across the class; UTI associations were inconsistent.
Impact: Provides precise, class-wide risk estimates for a common adverse event of widely used T2DM drugs, integrating RCT evidence with real-world pharmacovigilance.
Clinical Implications: Clinicians should counsel patients about high genital mycotic infection risk with SGLT-2 inhibitors, consider sex-specific susceptibility, and implement hygiene education and early treatment strategies; UTI risk warrants individualized assessment.
Key Findings
- Meta-analysis of 98 RCTs (91,756 participants) showed higher genital mycotic infection risk with SGLT-2 inhibitors vs placebo (RR 3.65) and vs active controls (RR 4.29).
- Subgroup differences were observed by individual SGLT-2 agent, sex, and treatment duration.
- FAERS disproportionality analyses showed consistent class-wide genitourinary infection signals; UTI associations were inconsistent across data sources.
Methodological Strengths
- Large-scale synthesis of 98 RCTs with prespecified outcomes and risk ratios
- Triangulation with FAERS using both frequentist and Bayesian disproportionality methods
Limitations
- Heterogeneity across RCTs and variable endpoint definitions may affect pooled estimates
- FAERS is subject to reporting bias and lacks denominators, limiting causal inference
Future Directions: Define patient-level risk factors (sex, circumcision status, prior candidiasis, glycemic control), evaluate preventive strategies, and standardize UTI endpoints across trials.
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) manage type 2 diabetes mellitus (T2DM) via increased urinary glucose excretion; however, their use is associated with an elevated risk of genitourinary infections. This study aims to evaluate this risk by synthesizing evidence from randomized controlled trials (RCTs) and characterizing clinical features using data from the FDA Adverse Event Reporting System (FAERS). METHODS: In this systematic review and meta-analysis, we searched PubMed and Embase up to June 2024 for RCTs reporting genital mycotic infection (GMI) and urinary tract infection (UTI) events associated with SGLT-2is. The primary outcome was the risk of GMI and UTI related to SGLT-2is, quantified using the risk ratio (RR) with a 95% confidence interval (CI). Additionally, a retrospective pharmacovigilance study of FAERS extracted the cases of genitourinary infections related to SGLT-2is up to June 2024. Disproportionality was calculated using the frequentist and bayesian based data mining algorithms. RESULTS: A total of 98 RCTs (91,756 participants) were included, treatment with SGLT-2is significantly increased the risk of GMI compared to placebo (RR: 3.65, 95% CI: 3.22- 4.14, p = <0.0001) and active control (RR: 4.29; 95% CI: 3.42-5.38, p = <0.0001). Subgroup analysis showed significant differences by individual drug, gender, and duration. Disproportionality analysis revealed significant signals for all SGLT-2is with genitourinary tract infections, persisting after signal refinement. CONCLUSION: SGLT-2is significantly increase the risk of GMI among T2DM patients, while the association with UTI remains inconsistent. Additional research is required to elucidate the potential risk factors.
3. Association between central obesity and the risk of glenohumeral joint osteoarthritis: a prospective study.
In 32,900 UK Biobank participants followed a median of 8.85 years, higher waist-to-height ratio (WHtR) predicted incident glenohumeral osteoarthritis independent of BMI. Risks were stronger in secondary GJO and in normal-BMI individuals with WHtR ≥0.5, with notable susceptibility in younger, female, and low-activity subgroups.
Impact: Demonstrates that central adiposity, captured by WHtR, adds risk information beyond BMI for shoulder osteoarthritis, supporting incorporation of fat distribution into musculoskeletal risk assessment.
Clinical Implications: Screening strategies for shoulder osteoarthritis risk may include WHtR to identify at-risk individuals, particularly those with normal BMI; lifestyle interventions targeting central obesity could be prioritized.
Key Findings
- Among 32,900 adults, baseline WHtR showed a significant linear association with incident GJO risk independent of BMI (AHR 1.52; 95% CI 1.02–2.26).
- Association was stronger in secondary GJO (AHR 1.74) and in normal-BMI individuals with WHtR ≥0.5 (AHR 1.94).
- Subgroups with higher risk included those <65 years, females, and individuals with insufficient physical or occupational activity.
Methodological Strengths
- Large prospective cohort (n=32,900) with nearly 9 years median follow-up
- Cox models with interaction and sensitivity analyses across BMI strata
Limitations
- Observational design limits causal inference despite adjustments
- Exposure assessed at baseline; time-varying changes in central adiposity were not captured
Future Directions: Elucidate mechanisms linking central adiposity to shoulder joint degeneration and test whether WHtR-guided lifestyle or metabolic interventions reduce GJO incidence.
BACKGROUND: The relationship between obesity and glenohumeral joint osteoarthritis (GJO) has long been a subject of doubt. Although body mass index (BMI) has been recognized as a risk factor by guidelines, it fails to reflect fat distribution, which may limit its clinical application value. Waist-to-height ratio (WHtR), as an indicator of central obesity, has shown good predictive performance in metabolic-related diseases. However, its role in GJO remains unclear. This study aimed to investigate the relationship between central obesity and GJO through a prospective cohort study in the UK Biobank. METHODS: We conducted a prospective cohort study based on the UK Biobank, including 32,900 adults who participated in the baseline survey between 2006 and 2014 and had no history of GJO. The median follow-up time was 8.85 years (IQR: 7.15-10.75). Cox proportional hazards models were used to assess the association between WHtR levels at baseline and the incidence of new GJO at the end of follow-up. Interaction and sensitivity analyses were conducted in different BMI strata. RESULTS: A significant linear correlation was observed between WHtR levels at baseline and the incidence risk of GJO at the end of follow-up (P < .001). Compared with individuals with normal WHtR at baseline, those with central obesity had a 1.52-fold increased risk of GJO (AHRs = 1.52, 95% CI: 1.02-2.26, P = .039), independent of BMI. Further analysis revealed that this association was more significant in the secondary GJO population (AHR = 1.74, 95% CI: 1.10-2.76, P = .019). Additionally, in the population with normal BMI at baseline, individuals with WHtR ≥0.5 had a 1.94-fold increased risk of GJO (AHRs = 1.94, 95% CI: 1.01-3.72, P = .046), but no significant association was observed in the population with overweight or obese BMI at baseline (P = .492; 0.998). Subgroup analysis showed that individuals under 65 year old, females, those with insufficient physical activity, and those with lower occupational physical activity had a higher risk (P = .014; 0.046; 0.005; 0.007). CONCLUSIONS: Central obesity is significantly associated with the risk of GJO, especially in the secondary GJO and normal BMI populations, suggesting that fat distribution should be included in the early screening and risk assessment system for GJO.