{"publication_id":"f0b4aa8b-f260-4fc6-8419-dac0b0a34715","screening":{"identified":42,"screened":42,"excluded":0,"included":42,"included_or_retained":42,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"42 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]},"limitations":["This is an agent-assisted evidence map, not a PRISMA-complete systematic review or clinical guideline.","It is not PROSPERO-registered and should not be read as medical advice.","Public sidecars expose citation traces and extraction status; empty fields mean not extracted, not assumed absent."],"contradictions":["In sum, the evidence supports class-level cardiorenal and mortality benefits of SGLT2 inhibitors that extend beyond glycemic control, yet the anti-aging case remains incomplete: cognitive and sarcopenia data are sparse, most longevity outcomes derive from post-hoc or observational designs rather than dedicated aging-focused RCTs, and the balance between metabolic benefit and lean-mass loss requires longitudinal characterization before SGLT2 inhibitors can be recommended for healthy aging outside their indications.","The corpus contains no sources classified primarily as direct interventional hard-endpoint evidence, 17 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence.","The thesis is: Across 42 curated reference papers, the evidence base for Sglt2 Inhibitors Effects shows a context-dependent profile. Positive signals appear in: contextual other, longevity. Negative signals appear in: cardiometabolic, contextual other. Null findings dominate: contextual other, cardiometabolic. The synthesis surfaces cross-study disagreements across outcome classes The Sglt2 Inhibitors Effects anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established. This thesis is treated as an organizing claim, not as a substitute for the study table, because the source record includes supportive, null, and adverse signals across different outcome classes.","The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.","The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.","Another tension arises between the neuroprotective and dementia-risk reduction signals of SGLT2 inhibitors and the absence of mechanistic clarity regarding how renal glucose excretion could protect the brain. This is a severity-5 disagreement within the contextual other outcome class. The mechanistic challenge is substantial: unlike cardiovascular benefits, which can be attributed to hemodynamic effects (preload reduction, afterload reduction, improved myocardial energetics via ketone body utilization), no established pathway connects renal glucose excretion to reduced amyloid deposition, tau phosphorylation, or neuroinflammation. Schonberger 2023 discusses immunomodulatory and anti-inflammatory effects of SGLT2 inhibitors, which could theoretically attenuate neuroinflammation, but this remains speculative without brain-specific biomarker data. The boundary condition for this tension is likely confounding by indication and healthy-user bias: patients prescribed SGLT2 inhibitors tend to have better metabolic profiles and more intensive overall diabetes management, which are themselves protective against cognitive decline. The evidence needed to resolve this tension includes Mendelian randomization studies using genetic instruments for SGLT2 activity and brain MRI biomarker endpoints in SGLT2 inhibitor trials, neither of which currently exist in the literature."]}