Your weekly SGLT2 article review 
GLP-1RA comparative effectiveness against dementia onset relative to other antidiabetic medications in a large, multi-site cohort of patients with type 2 diabetes 2025
Overall, our results are consistent with prior observational analyses comparing GLP-1RA to DPP4i or SU in diabetic populations and reinforce previous findings that GLP-1RA may be protective against dementia, but not to a greater extent than SGLT2i.
Comparative Risk of Glaucoma in Patients Using Sodium-glucose Cotransporter-2 Inhibitors and Metformin: A Multinational Cohort Study 2025
Compared to metformin, SGLT2 inhibitors are associated with significantly lower risks of ocular hypertension (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.60–0.89), POAG (HR, 0.64; 95% CI, 0.51–0.81), and the need for glaucoma medications (HR, 0.76; 95% CI, 0.69–0.84) in 5 years.
Empagliflozin for the preservation of beta-cell function in women with recent gestational diabetes: A randomized placebo-controlled trial 2025
The primary outcome of baseline-adjusted ISSI-2 at 48 weeks was not different between the empagliflozin and placebo group (525 ± 30.4 vs. 560 ± 33.4, p = 0.43). Additional measures of beta-cell function, insulinogenic index/HOMA-IR, and ΔCpep0-120/Δgluc0-120 × Matsuda index also did not differ between the groups. While there was no difference in the secondary outcome of prevalence of dysglycemia at 48 weeks between the arms (empagliflozin 65.7% vs. 48.2% in placebo, p = 0.18), the glucose tolerance worsened in 9.4% of participants in the empagliflozin group as compared to 28% in the placebo group (p = 0.08).
Impact of Empagliflozin Versus Dapagliflozin on Left Ventricular Remodeling in Heart Failure Patients: A 1-Year Comparative Study 2025
Both SGLT2is significantly improved E-wave deceleration time, LAVI, LV-EDVI, LV-ESVI, LV-MI, and LVEF. Neither medication produced significant changes in RWT, and no significant differences were noted between groups regarding HF hospitalizations or all-cause mortality.
Empagliflozin demonstrated more pronounced effects on LV remodeling markers, including peak E-wave velocity, E/e’ ratio, and LV-SI, compared to dapagliflozin.
Enhancing evidence-based guidelines using trial emulation in electronic health records: Real-world effects of empagliflozin in people with type 2 diabetes 2025
There is growing interest in expanding SGLT2i use to broader populations, with draft UK National Institute for Health and Care Excellence (NICE) 2025 guidelines proposing it as first-line therapy for all people with T2DM, in combination with metformin.
These findings provide critical real-world evidence supporting a universal SGLT2i strategy in T2DM management, which is of direct relevance to current guideline deliberations.
Association between SGLT2 inhibitors and genital cancer: a meta-analysis and mendelian randomization study 2025
A total of 15 studies (16 trials) involving 101,430 patients were included. SGLT2 inhibitors did not significantly reduce genital cancer risk compared to placebo (RR 1.10; 95% CI 0.93–1.31; P = 0.28; moderate certainty of evidence), with consistent findings across subgroup analyses. No significant effects of SGLT2 inhibitors were observed for cervical, endometrial, ovarian, prostate, uterine, penile, or vulvar cancers. Dapagliflozin potentially increased the risk of male genital cancers (RR 1.31; 95% CI 0.99–1.74; P = 0.06). SGLT2 inhibition significantly reduced testicular [odds ratio (OR) 0.012; 95% CI 0.001–0.220; P = 0.003] and cervical (OR 0.013; 95% CI 0.001–0.122; P = 1.615 × 10 − 4) cancer risks. Pooled results from both discovery and replication cohorts demonstrated that SGLT2 inhibition reduced cervical cancer risk (OR 0.016; 95% CI 0.002–0.116; P < 0.0001).
SGLT2 inhibitors exhibited a neutral overall risk profile for genital cancers, while genetic evidence demonstrated beneficial effects specifically for cervical cancer.
Impact of Empagliflozin and Dapagliflozin on Sudden Cardiac Death: A Systematic Review and Meta-Analysis of Adjudicated Randomized Evidence 2025
To assess the effect of empagliflozin and dapagliflozin on SCD in patients with type 2 diabetes, heart failure, or chronic kidney disease.
A systematic review and meta-analysis were conducted on randomized controlled trials. A total of 58,569 participants from 8 trials were included, with 30,565 patients treated with SGLT2 inhibitors and 28,104 controls assigned to placebo. The median follow-up period was 29 months. We performed pooled analysis, meta-regression, and subgroup analyses to explore the impact on SCD risk across different populations and treatment regimens.
The pooled analysis showed a reduced risk of SCD with SGLT2 inhibitors (OR: 0.82; 95% CI: 0.72–0.94; p = 0.0104), with negligible heterogeneity (τ2 = 0.0000; I2 = 0.0%; Q = 3.17, p = 0.8687). Subgroup-specific estimates (age, follow-up duration, population, and SGLT2 inhibitor type) did not reach statistical significance. Meta-regression showed no significant moderation by mean age, study duration, or gender. No evidence of publication bias was detected.
Empagliflozin and dapagliflozin may reduce the relative risk of sudden cardiac death. These data expand the spectrum of cardiovascular benefits attributed to SGLT2 inhibition. Further trials specifically designed to address pre-adjudicated arrhythmic endpoints are warranted.
@CronosTempi: interesting that they pooled T2D, HF and CKD and still found benefits.
Preprint: Comparative effectiveness of empagliflozin versus dapagliflozin in adults with metabolic dysfunction-associated steatotic liver disease 2025
In patients with MASLD, empagliflozin was associated with better clinical outcomes compared to dapagliflozin, particularly in reducing cardiovascular and renal events, hospitalizations, and mortality.
On the complexity of polypharmacy (in a rare disease + animal model but still interesting): Dapagliflozin with losartan but not olmesartan has an add-on protective effect in experimental Alport syndrome 2025
And now the less good news (in special subpopulations though):
Comparative Analysis of Arrhythmia Risk: SGLT2 inhibitors versus GLP-1 Receptor Agonists in Patients with Type 2 Diabetes and Inflammatory Arthritis 2025
Patients treated with SGLT2 inhibitors demonstrated significantly higher rates of atrial fibrillation (10.4% vs 7.8%, HR 1.552, 95% CI 1.303-1.848, p<0.001) and ventricular tachycardia (4.8% vs 2.2%, HR 2.467, 95% CI 1.825-3.334, p<0.001) compared to those receiving GLP-1 receptor agonists. Ventricular fibrillation was also more common in the SGLT2 inhibitor group (2.4% vs 0.8%, HR 3.451, 95% CI 2.131-5.590, p<0.001).
Sodium Glucose Co-transporter 2 Inhibitors In Left Ventricular Assist Device Patients: A Double-Edged Sword in Advanced Heart Failure; Insight from Propensity-Matched, Real-World Multicentric Analysis 2025
SGLT2i use was associated with a 30.5% reduction in all-cause mortality (CI -33%, -28%, P < 0.0001, OR 0.228), however, SGLT2i users noted to have higher rates of drive-line infection (CI 1.39%, 5.55%, P <0.001, OR 1.32), right heart failure (CI 11.69%, 17.00%, P<0.0001, OR 2) and cardiorenal syndrome (7.13%,12.94%, P<0.0001, OR 1.49). No significant difference was observed in atrial fibrillation incidence between the two cohorts.
. Yes, I am a little sick in the head, why do you ask 
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