Derivation Web

source_a3c78babef194a8d

by researka:v2 · 2026-06-20 00:34:54.222326+04:00

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The conclusion therefore does not support broad causal, clinical, or policy claims.", "type": "claim"}, {"id": "claim_2", "text": "This paper synthesizes evidence on Alpha-glucosidase inhibitor across 14 included source papers and 1146 high-confidence extracted claims.", "type": "claim"}, {"id": "claim_3", "text": "The evidence profile contains 2 direct clinical sources, 12 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 27 cross-study disagreements across the evidence base.", "type": "claim"}, {"id": "claim_4", "text": "Positive study-level signals are not the dominant direction in any outcome class; null signals are summarized in the contextual adjacent evidence outcome class; negative signals are not the dominant direction in any outcome class; mixed or heterogeneous signals are summarized in the cardiometabolic and longevity outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "type": "claim"}, {"id": "claim_5", "text": "The conclusion is that Alpha-glucosidase inhibitor should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.", "type": "claim"}, {"id": "claim_6", "text": "For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.", "type": "claim"}, {"id": "claim_7", "text": "Aging is the dominant driver of chronic disease, frailty, and functional decline in older adults, and the question of whether pharmacological interventions can extend healthspan — the portion of life spent in good health — has become one of the most active questions in geriatric medicine (Studenski 2011). The demographic stakes are considerable: global life expectancy has risen steadily, yet the years lived with multimorbidity and mobility limitation have risen in parallel, motivating the search for interventions that compress morbidity rather than merely prolong survival (Cesari 2009). Functional markers such as gait speed, with small clinically meaningful changes on the order of 0.1 m/s (Perera 2006) and average annual declines near 0.05 m/s (Bohannon 1997), provide quantitative anchors against which any candidate geroprotector must eventually be judged. The economic and humanitarian case for delaying aging-related decline has therefore moved aging biology from a descriptive science to an interventional target, and the question of whether existing, widely used drugs can be repositioned to that end appears increasingly urgent. This synthesis is situated at that intersection: it asks what the current human evidence base does and does not say about acarbose as a candidate gerotherapeutic. Importantly, the evidence reviewed here may inform — but cannot by itself settle — the broader question of whether acarbose meaningfully alters human aging trajectories.", "type": "claim"}, {"id": "claim_8", "text": "The geroscience hypothesis proposes that targeting the biological mechanisms of aging — rather than any single disease — may simultaneously delay multiple age-related conditions, and that pharmacological modulation of those mechanisms is therefore a rational therapeutic strategy (Anisimov 2008). Within this framework, drug repurposing offers practical advantages: the safety, pharmacokinetic, and manufacturing profiles of approved agents are already characterized, potentially shortening the path from preclinical signal to human trial (Ioannidis 2005). This logic has energized systematic efforts to screen compounds originally developed for metabolic disease against canonical longevity endpoints, and acarbose has emerged as one of the candidates repeatedly highlighted in such programs. The geroscience framing also implies a hierarchy of evidence: mechanistic plausibility in model organisms is necessary but not sufficient, and the field has learned that surrogate biomarkers do not guarantee hard-outcome benefit (Ioannidis 2005). Accordingly, the translational bar for any repurposed agent is high — preclinical lifespan extension must be reconciled with human randomized evidence on clinically meaningful endpoints before claims of geroprotection can be entertained. The remainder of this introduction situates acarbose against that bar.", "type": "claim"}, {"id": "claim_9", "text": "Acarbose is an alpha-glucosidase inhibitor of the metabolic drug class that has been prescribed for decades, primarily to blunt postprandial glucose excursions in patients with type 2 diabetes, and it is this long clinical history — rather than any recent molecular innovation — that makes it a candidate of interest for aging research. By delaying intestinal carbohydrate digestion, the drug appears to attenuate postprandial glycemic and hemodynamic responses, and these acute physiological effects have been hypothesized to translate into longer-term cardiometabolic and possibly longevity benefits. The drug's regulatory status, broad generic availability, and well-characterized safety profile lower the practical barriers to designing long-duration human studies in non-diabetic older adults, an important consideration given the multi-year follow-up any aging endpoint requires. It is precisely this combination — plausible mechanism, decades of human use, and established dosing — that has prompted the field to ask whether acarbose may function as a gerotherapeutic, a question the remainder of this synthesis will address with explicit attention to the limits of current evidence.", "type": "claim"}, {"id": "claim_10", "text": "The human randomized evidence landscape for acarbose is heterogeneous in design, population, and endpoint, ranging from mechanistic biomarker trials in type 2 diabetes to weight-management studies in overweight adults and pharmacodynamic bioequivalence work in healthy volunteers (Yang 2025; Holmback 2025; Lobato 2026). Several systematic reviews and meta-analyses have aggregated the cardiometabolic literature, reporting signals on triglycerides, total cholesterol, and postprandial blood pressure that are directionally favorable but variable in magnitude and statistical certainty (Yousefi 2023; Wang 2021; Madden 2025). The central interpretive challenge is therefore that acarbose has been studied in many trials, but rarely in trials whose primary endpoint is aging itself; the question of whether the existing human RCT evidence, Across the corpus, supports a geroprotective claim remains, as the field acknowledges, unsettled.", "type": "claim"}, {"id": "claim_11", "text": "The background evidence for Alpha-glucosidase inhibitor is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Yang 2025, Lobato 2026 are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation.", "type": "claim"}, {"id": "claim_12", "text": "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.", "type": "claim"}, {"id": "claim_13", "text": "Across the retained sources, positive signals cluster around the contextual adjacent evidence and cardiometabolic outcome classes; null signals around the contextual adjacent evidence and cardiometabolic outcome classes; and negative or adverse signals around no dominant outcome class. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.", "type": "claim"}, {"id": "claim_14", "text": "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.", "type": "claim"}, {"id": "claim_15", "text": "The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.", "type": "claim"}, {"id": "claim_16", "text": "The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.", "type": "claim"}, {"id": "claim_17", "text": "Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses).", "type": "claim"}, {"id": "claim_18", "text": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, longevity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.", "type": "claim"}, {"id": "claim_19", "text": "Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.", "type": "claim"}, {"id": "claim_20", "text": "Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.", "type": "claim"}, {"id": "claim_21", "text": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "type": "claim"}, {"id": "claim_22", "text": "| Contextual Adjacent Evidence | n=6; claims=686 | no extracted directional signal in 4/6 sources | 2 direct; 3 indirect; 1 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_23", "text": "Contextual Adjacent Evidence: n=6; claims=686; no extracted directional signal in 4/6 sources | directness: 2 direct; 3 indirect; 1 review; main limitation: directionally heterogeneous.", "type": "claim"}, {"id": "claim_24", "text": "Quantitative findings are heterogeneous across source-anchored effect estimates. Madden 2025 attenuated the postprandial systolic blood pressure decline (standardized β = 0.724 ± 0.286, P = 0.017) in older adults, with a secondary contrast at P = 0.040. The Zhang 2020 network meta-analysis distinguished glucose-lowering comparability (P > 0.05) from weight-loss superiority at P < 0.05, P = 0.011, and P = 0.000. Yu 2021 reported a non-significant BMI reduction versus placebo (P = 0.56) in non-diabetic overweight and obese adults. Detailed per-study × endpoint tuples are catalogued in the evidence synthesis.", "type": "claim"}, {"id": "claim_25", "text": "The contextual outcome class contains the largest concentration of evidence in the acarbose corpus, with six sources spanning mechanistic biomarker RCTs, observational cohorts, bioequivalence studies, and one systematic review. Yousefi 2023 is a systematic review and meta-analysis of randomized clinical trials evaluating acarbose on adult lipid profiles. Lobato 2026 is the HypoBar I randomised, double-blinded, cross-over, placebo-controlled trial of placebo, acarbose 50 mg thrice daily, or canagliflozin for post-bariatric hypoglycaemia. Xu 2020 evaluates pharmacodynamic bioequivalence in adults.", "type": "claim"}, {"id": "claim_26", "text": "Mechanistically, the contextual outcomes map onto two distinct human pathways. In a clinical RCT design, Yang 2025 directly probed the gut-microbiota-derived metabolite TMAO and its上下游 (upstream/downstream) intermediaries, supporting the mechanistic substrate of α-glucosidase inhibition reshaping microbial fermentation products. Preclinical and clinical bioequivalence data from Chen 2021 and Xu 2020 trace a complementary pharmacodynamic pathway: a 200-mg acarbose dose can reduce starch absorption by approximately the proportion noted in the Xu 2020 excerpt, anchoring the linkage between gastrointestinal enzyme blockade and post-prandial glucose handling. Yousefi 2023 and Song 2021 extend these mechanisms into systemic cardiometabolic territory, with reduced triglycerides and reduced low-grade albuminuria suggesting downstream hepatic and renal sequelae of intestinal carbohydrate modulation.", "type": "claim"}, {"id": "claim_27", "text": "Within-corpus tensions are pronounced in this outcome class. Yousefi 2023 (positive direction on lipid outcomes) stands in partial conflict with Xu 2020 and Chen 2021, which returned null or equivalence-class findings on pharmacodynamic and pharmacokinetic parameters — a null vs positive tension. Indirectness_gap tensions further stratify the evidence: Yang 2025 (direct, biomarker A1 endpoint) and Lobato 2026 (direct, post-bariatric glycaemic endpoint) are both anchored on direct mechanistic or clinical endpoints, whereas Song 2021, Chen 2021, and Xu 2020 provide indirect contextual support, and Yousefi 2023 functions as an aggregating review. The boundary conditions — baseline microbiota composition, dietary starch load, renal function, and prior bariatric surgery — remain to be established before any single contextual claim can be generalized.", "type": "claim"}, {"id": "claim_28", "text": "Concretely, hazard ratios in the 2.92-3.03 band indicate that treated females experienced roughly a three-fold higher instantaneous mortality hazard than controls during the post-treatment window, which is a directionally adverse longevity effect in this species and sex stratum. By contrast, the same review reports that rapamycin produced a strongly favourable hazard ratio of 0.42 with P < 0.001 in the analogous post-treatment survival analysis, so the within-corpus contrast between agents is large and statistically supported on both sides (Liao 2025). The acarbose effect size of HR ≈ 2.92-3.03 therefore represents the opposite pole of the gerotherapeutic spectrum represented in this review, and the survival disadvantage was specific to females rather than reported as a pooled-sex effect. Because Liao 2025 is the only longevity source, no other survival effect estimate can be cross-checked against an independent source within the corpus, and the evidence synthesis (Per-Study Endpoint Evidence) carries the full hazard-ratio and P-value tuple for the reader.", "type": "claim"}, {"id": "claim_29", "text": "Mechanistically, the survival disadvantage reported for acarbose in female crickets can be read against the canonical acarbose pharmacology of intestinal α-glucosidase inhibition and consequent blunting of post-prandial glucose excursions, a substrate-level mechanism that has been linked in mammalian mechanistic human studies and preclinical data to attenuated glycaemic load and downstream mTOR-related nutrient-sensing pathways (Liao 2025). In the cricket model, however, the same pharmacological class appears to act in the opposite direction on survival, which suggests that the gerotherapeutic translation of α-glucosidase inhibition is not species-invariant and may depend on baseline dietary carbohydrate composition, sex-specific metabolic set-points, or microbiome composition that differs between orthopterans and mammals. The mechanistic substrate underlying this functional finding therefore cannot be cleanly extrapolated from the Liao 2025 invertebrate signal to human longevity, and any mechanistic narrative must be qualified as preclinical, sex-stratified, and non-mammalian in origin. Preclinical data from this systematic review thus function here as a hypothesis-generating boundary condition rather than as confirmatory human-relevant evidence.", "type": "claim"}, {"id": "claim_30", "text": "The most load-bearing cross-domain tension in the acarbose corpus is the dislocation between preclinical longevity signaling and human RCT outcomes — a tension that the integrating brief explicitly flags as incomplete. Against this negative invertebrate signal, the human RCT evidence on longevity-adjacent hard endpoints is essentially absent from the sources: there is no human survival or healthspan trial of acarbose, only biomarker-endpoint RCTs (Yang 2025) and surrogate-driven observational cohorts (Zhang 2021). The mechanistic–clinical boundary condition here is straightforward — an invertebrate finding, even a statistically robust one, cannot be transposed onto human longevity claims, and a negative cricket result should not be ignored because the human data are merely silent rather than supportive.", "type": "claim"}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1186/s40360-023-00706-6", "effect": "not extracted", "endpoint": "not extracted", "id": "source_1", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The effect of acarbose on lipid profiles in adults: a systematic review and meta-analysis of randomized clinical trials", "type": "source", "url": "https://doi.org/10.1186/s40360-023-00706-6", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41598-021-84015-0", "effect": "not extracted", "endpoint": "not extracted", "id": "source_2", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The effects of acarbose therapy on reductions of myocardial infarction and all-cause death in T2DM during 10-year multifactorial interventions (The Beijing Community Diabetes Study 24)", "type": "source", "url": "https://doi.org/10.1038/s41598-021-84015-0", "year": 2021}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1111/dom.14661", "effect": "not extracted", "endpoint": "not extracted", "id": "source_3", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Efficacy and safety of alogliptin versus acarbose in Chinese type 2 diabetes patients with high cardiovascular risk or coronary heart disease treated with aspirin and inadequately controlled with metformin monotherapy or drug‐naive: A multicentre, randomized, open‐label, prospective study ( ACADEMIC", "type": "source", "url": "https://doi.org/10.1111/dom.14661", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.2147/DMSO.S325683", "effect": "not extracted", "endpoint": "not extracted", "id": "source_4", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Acarbose Reduces Low-Grade Albuminuria Compared to Metformin in Chinese Patients with Newly Diagnosed Type 2 Diabetes", "type": "source", "url": "https://doi.org/10.2147/DMSO.S325683", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/oby.24369", "effect": "not extracted", "endpoint": "not extracted", "id": "source_5", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The Supportive Effect of Acarbose to Orlistat in Weight Management—A Randomized, Double‐Blind, Multiarm Phase 2 Trial", "type": "source", "url": "https://doi.org/10.1002/oby.24369", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fendo.2025.1575087", "effect": "not extracted", "endpoint": "not extracted", "id": "source_6", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effect of acarbose and vildagliptin on plasma trimethylamine N-oxide levels in patients with type 2 diabetes mellitus: a 6-month, two-arm randomized controlled trial", "type": "source", "url": "https://doi.org/10.3389/fendo.2025.1575087", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3389/fendo.2020.00288", "effect": "not extracted", "endpoint": "not extracted", "id": "source_7", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Acarbose With Comparable Glucose-Lowering but Superior Weight-Loss Efficacy to Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials", "type": "source", "url": "https://doi.org/10.3389/fendo.2020.00288", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/cpdd.921", "effect": "not extracted", "endpoint": "not extracted", "id": "source_8", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Evaluation of the Bioequivalence of Acarbose in Healthy Chinese People", "type": "source", "url": "https://doi.org/10.1002/cpdd.921", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/dom.70611", "effect": "not extracted", "endpoint": "not extracted", "id": "source_9", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Acarbose or Canagliflozin vs. Placebo to Ameliorate Post‐Bariatric Hypoglycaemia: The Clinical Outcomes of the HypoBar I Randomised Clinical Trial", "type": "source", "url": "https://doi.org/10.1111/dom.70611", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1177/0300060520960317", "effect": "not extracted", "endpoint": "not extracted", "id": "source_10", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Method for evaluating the human bioequivalence of acarbose based on pharmacodynamic parameters", "type": "source", "url": "https://doi.org/10.1177/0300060520960317", "year": 2020}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3389/fcvm.2021.663635", "effect": "not extracted", "endpoint": "not extracted", "id": "source_11", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Acarbose for Postprandial Hypotension With Glucose Metabolism Disorders: A Systematic Review and Meta-Analysis", "type": "source", "url": "https://doi.org/10.3389/fcvm.2021.663635", "year": 2021}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1017/s0714980825100056", "effect": "not extracted", "endpoint": "not extracted", "id": "source_12", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The Effects of Acarbose on the Postprandial Hypotensive Response in Older Adults.", "type": "source", "url": "https://doi.org/10.1017/s0714980825100056", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1101/2025.08.25.671822", "effect": "not extracted", "endpoint": "not extracted", "id": "source_13", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The gerotherapeutic drugs rapamycin, acarbose, and phenylbutyrate extend lifespan and enhance healthy aging in house crickets", "type": "source", "url": "https://doi.org/10.1101/2025.08.25.671822", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1007/s12325-020-01602-9", "effect": "not extracted", "endpoint": "not extracted", "id": "source_14", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The Effects of Acarbose on Non-Diabetic Overweight and Obese Patients: A Meta-Analysis.", "type": "source", "url": "https://doi.org/10.1007/s12325-020-01602-9", "year": 2021}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_15", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_16", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Directness** is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_17", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Directional signal** is counted within the assigned outcome class only. A `no extracted directional signal` cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_18", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Evidence tier** follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1001/jama.2010.1923", "effect": "not extracted", "endpoint": "not extracted", "id": "source_19", "intervention_or_exposure": "not 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"citation", "doi": "10.1056/NEJMoa1504347", "effect": "not extracted", "endpoint": "not extracted", "id": "source_27", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Tancredi 2015", "type": "source", "url": "https://doi.org/10.1056/NEJMoa1504347", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1371/journal.pmed.0020124", "effect": "not extracted", "endpoint": "not extracted", "id": "source_28", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Ioannidis 2005", "type": "source", "url": "https://doi.org/10.1371/journal.pmed.0020124", "year": null}], "publication_id": "08943c0f-97ab-41e2-820b-bf2dbe384513", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", 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