Evidence mapPaperPMID 40842430Full record

ArticlePhysiological reports2025

Metabolic shifts in plasma amino acids and related metabolites in response to SGLT2 inhibition and hyperglycemia in type 1 diabetes.

Luxcia Kugathasan, Nagarjunachary Ragi, Subrata Debnath, Vikas S Sridhar, Soumya Maity, Tianqing Feng, Esmeralda Treviño, Bruce A Perkins, David Z I Cherney, Kumar Sharma

Abstract read
In one paragraph

Article in Physiological reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Luxcia KugathasanDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0002-1802-9253
Nagarjunachary RagiCenter for Precision Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Subrata DebnathCenter for Precision Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Vikas S SridharDivision of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada.
Soumya MaityCenter for Precision Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Tianqing FengCenter for Precision Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Esmeralda TreviñoCenter for Precision Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Bruce A PerkinsLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
David Z I CherneyDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.
Kumar SharmaCenter for Precision Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.

Funding

Boehringer Ingelheim (BI)Eli Lilly and Company (Lilly)
6 · The paper itself

Abstract

Regulated kidney function is dependent on maintaining efficient energy utilization. Our aim in this study was to determine the effects of acute, ambient hyperglycemia and sodium-glucose cotransporter-2 (SGLT2) inhibition on plasma amino acid metabolism in patients with type 1 diabetes (T1D). The ATIRMA trial, a single-arm study, evaluated the effects of 8 weeks of oral empagliflozin (25 mg/day) in 40 young adults with T1D. The study involved consecutive two-day assessments of clamped euglycemia and hyperglycemia at both baseline and post-treatment. MetaboAnalyst 6.0 categorized 35 metabolites into significant pathways, which were statistically compared using principal component analysis. Acute hyperglycemia induced changes to 10 metabolic pathways, including but not limited to increases in cysteine and methionine metabolism (0.52 ± 0.12, p < 0.0001), valine, leucine, and isoleucine biosynthesis (0.31 ± 0.10, p = 0.002); and nitrogen metabolism (0.11 ± 0.03, p = 0.003). Introduction of empagliflozin was associated with a decrease in adenine, and an increase in cysteine and methionine metabolism (0.31 ± 0.13, p = 0.02) when maintained under euglycemia and a decrease in nitrogen metabolism under hyperglycemia (-0.07 ± 0.04, p = 0.04). Our findings show that SGLT2 inhibition counteracts the hyperglycemia-induced changes in plasma amino acid metabolism, potentially improving energy efficiency and metabolic health, though more research is needed to confirm these metabolic effects.

Indexed as

Amino AcidsBenzhydryl CompoundsDiabetes Mellitus, Type 1GlucosidesHyperglycemiaSodium-Glucose Transporter 2 InhibitorsAdultBlood GlucoseFemaleHumansMaleYoung AdultAmino AcidsBenzhydryl CompoundsBlood GlucoseempagliflozinGlucosidesSodium-Glucose Transporter 2 Inhibitorsamino acidsempagliflozinhyperglycemiametabolitesSGLT2 inhibitiontype 1 diabetes

Identifiers

PMID40842430
PMCPMC12371268

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.