SGLT2 vs GLP-1RAs:
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Comparative Effects of SGLT2 Inhibitors and Incretin-Based Therapies on Dementia Risk in Type 2 Diabetes: A Systematic Review and Meta-analysis 2025: “Results: Nine studies were identified for analysis. Compared with incretin mimetics, SGLT2is significantly reduced the overall dementia risk [hazard ratio (HR) 0.82, 95% CI: 0.73-0.91], and SGLT2is had stronger effects than DPP-4i (HR 0.67, 95% CI: 0.59-0.77) and GLP-1RA (HR 0.93, 95% CI: 0.86-1.00). SGLT2i also reduced the risks of vascular dementia and Alzheimer’s disease (HR 0.49, 95% CI: 0.35–0.70 vs. HR 0.68, 95% CI: 0.52–0.88, respectively). The results of subgroup analyses revealed increased benefits for patients aged older than 65 years. Empagliflozin was the most consistently protective among the SGLT2i agents.”
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A systematic review and meta-analysis comparing the cardiovascular effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 agonists in type 2 diabetes 2025: “Compared to GLP-1 agonist, SGLT2 inhibitor use was associated with a significant 18% reduced risk of heart failure in T2DM patients, while a non significantly reduced risk of MACE, all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke. In T2DM patients with pre-existing CVD, SGLT2 inhibitors showed a significant 14% reduced risk of heart failure, 10% reduced risk of myocardial infarction, and 7% borderline reduced risk of all-cause mortality compared to GLP-1 agonists.”
Do SGLT2 Inhibitors Improve Cardiovascular Outcomes After Acute Coronary Syndrome Regardless of Diabetes? A Systematic Review and Meta-Analysis 2025
Initiation of SGLT2 inhibitors after ACS is associated with a significant reduction in all-cause and CV mortality. Subgroup analysis further demonstrated a reduction in all-cause mortality and recurrent myocardial infarction among patients with T2DM, while in patients without diabetes, no significant effects were observed.
When stratified by diabetes status, convergent patterns emerged regarding the CV mortality benefit of SGLT2 inhibitors. Among patients with diabetes, the complementary analysis showed a pooled HR of 0.69 (95% CI: 0.45–1.06, p = 0.07). Although this did not reach statistical significance, and heterogeneity was moderate (I2 = 67.6%), Figure 4C. Despite the lack of statistical significance in the HR model, the evidence shows that SGLT2 inhibitors may confer CV mortality benefit in this high-risk population. In the subgroup without diabetes, the pooled HR was 0.88 [95% CI 0.73–1.07, p = 0.12], not reaching statistical significance, Figure 4B. However, the consistency in direction of effect favoring SGLT2 inhibitors in both analyses suggests a potential benefit even in patients without diabetes.
Good news: SGLT2 Inhibitors and the Risk of Infections in Type 2 Diabetes: Systematic Review and Meta-Analyses of Real-World Evidence 2025
From 6827 records, 28 studies were included in qualitative synthesis and 14 in meta-analyses. There was no association with COVID-19-related mortality in seven studies (OR 0.91; 95% CI: 0.57–1.46) or COVID-19-related hospitalisation in three studies (OR 0.90; 95% CI: 0.67–1.20). A reduced risk of pneumonia was observed in three studies (HR: 0.61; 95% CI: 0.57–0.66), a reduced risk of pneumonia-related mortality in two studies (HR: 0.49; 95% CI: 0.35–0.67), and a reduced risk of sepsis in three studies (HR: 0.45; 95% CI: 0.30–0.68).
SGLT1 vs SGLT2, the debate continues @Neo: Sodium-glucose cotransporter 1 inhibition may delay aging: a Mendelian randomization study 2025
Finally, the exposure data for SGLT1 inhibition were derived from the UK Biobank, including 344,182 European individuals. The GWAS data for telomere length included 472,174 participants, and for frailty index, 175,226 individuals were included. Sixteen single nucleotide polymorphisms (SNPs) that met the SNP screening criteria were retrieved. The results indicated that SGLT1 inhibition increases telomere length (odds ratio [OR]IVW = 1.10, 95% CI: 1.03–1.18; p = 0.007) and reduces the frailty index (OR IVW = 0.84, 95% CI: 0.73–0.95; p = 0.008). No evidence of significant pleiotropy or heterogeneity was observed, which was further substantiated by the sensitivity analysis results.
Empa vs dapa:
Mechanism: The SGLT2 inhibitor empagliflozin promotes increased fatty acid oxidation in skeletal muscle cells 2025
In summary, treatment of skeletal muscle cells in vitro with EMPA caused changes in energy metabolism promoting enhanced fatty acid and leucine catabolism, decreased metabolism of glucose and acetoacetate, and reduced glycolysis. The observed changes in energy metabolism may be related to AMPK activation.
SGLT2 Inhibitors and Prevention of Cardiovascular Events in Diabetes Patients with and Without Hypertension: A Nationwide Cohort Study 2025
This nationwide cohort study demonstrates that in T2D patients without cardiovascular disease, SGLT2i use is associated with a lower risk of coronary heart disease, stroke, heart failure, and MACE in those with hypertension. In patients without hypertension, SGLT2i use was linked to a reduced risk of atrial fibrillation, suggesting its potential role in the primary prevention of cardiovascular events for T2D patients.
The impact of dynamic kidney function prior to using sodium-glucose cotransporter-2 inhibitors in type 2 diabetes patients with low-risk renal disease progression 2025
Early initiation of SGLT2i among type 2 diabetes patients with low-risk renal disease progression and glomerular injury renal status may prevent them from progressing into chronic kidney disease.
