Evidence mapPaperPMID 37738423Full record

ArticleThe Journal of clinical endocrinology and metabolism2024

Vitamin D Deficiency Increases Vulnerability to Canagliflozin-induced Adverse Effects on 1,25-Dihydroxyvitamin D and PTH.

Zhinous Shahidzadeh Yazdi, Elizabeth A Streeten, Hilary B Whitlatch, May E Montasser, Amber L Beitelshees, Simeon I Taylor

Erratum issued Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It reports registered trial NCT02891954. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 24% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02891954 phase1active not recruiting

Pharmacogenomics to Predict Responses to SGLT2 Inhibitors

Ran2016Enrolled700Registered outcomes7Posted comparisons0ConditionsDiabetes Mellitus, Type 2ArmsCanagliflozin
Open the trial in the graph
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Critical Role for 24-Hydroxylation in Homeostatic Regulation of Vitamin D Metabolism.The Journal of clinical endocrinology and metabolism · 2025 · on this map
    Article
  3. Article
  4. Critical Role for 24-Hydroxylation in Homeostatic Regulation of Vitamin D Metabolism.medRxiv : the preprint server for health sciences · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Zhinous Shahidzadeh YazdiDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0003-1056-4523
Elizabeth A StreetenDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Hilary B WhitlatchDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
May E MontasserDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Amber L BeitelsheesDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Simeon I TaylorDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0001-7500-7854
University of Maryland, Baltimore · US

Funding

Diabetes, Obesity, and Metabolic ComplicationsT32DK098107 · UNIVERSITY OF MARYLAND BALTIMORE · 2025 to 2025
$274k
NIDDK NIH HHSNIDDK NIH HHS R01 DK118942NIDDK NIH HHS T32 DK098107
6 · The paper itself

Abstract

contextCanagliflozin has been reported to increase the risk of bone fracture-possibly mediated by decreasing 1,25-dihydroxyvitamin D (1,25(OH)2D) and increasing parathyroid hormone (PTH).

objectiveThis work investigated whether baseline vitamin D (VitD) deficiency renders individuals vulnerable to this adverse effect and whether VitD3 supplementation is protective.

methodsThis community-based, outpatient study had a paired design comparing individual participants before and after VitD3 supplementation. Eleven VitD-deficient (25-hydroxyvitamin D [25(OH)D] ≤ 20 ng/mL) individuals were recruited from the Amish population in Lancaster, Pennsylvania. Participants underwent 2 canagliflozin challenge protocols (300 mg daily for 5 days): the first before and the second after VitD3 supplementation. In the VitD3 supplementation protocol, participants received VitD3 supplementation (50 000 IU once or twice a week depending on body mass index for 4-6 weeks) to achieve 25(OH)D of 30 ng/mL or greater. Two coprimary end points were identified: effects of VitD3 supplementation on canagliflozin-induced changes in 1,25(OH)2D and PTH. Secondary end points included effects of VitD3 supplementation on baseline levels of VitD metabolites and PTH.

resultsVitD3 supplementation increased mean 25(OH)D from 16.5 ± 1.6 to 44.3 ± 5.5 ng/mL (P = .0006) and 24,25-dihydroxyvitamin D (24,25(OH)2D) from 1.0 ± 0.1 to 4.3 ± 0.6 ng/mL (P = .0002). Mean 1,25(OH)2D and PTH were unchanged. VitD3 supplementation decreased the magnitude of canagliflozin-induced changes in 1,25(OH)2D (from -31.3%±4.7% to -9.3%±8.3%; P = .04) and PTH (from +36.2%±6.2% to +9.7%±3.7%; P = .005).

conclusionVitD deficiency rendered individuals more vulnerable to adverse effects of canagliflozin on biomarkers associated with bone health. VitD3 supplementation was protective against canagliflozin's short-term adverse effects on 1,25(OH)2D and PTH.

Indexed as

Parathyroid HormoneVitamin D DeficiencyCanagliflozinDietary SupplementsErgocalciferolsHumansVitamin DVitamins1,25-dihydroxyvitamin DCanagliflozinErgocalciferolsParathyroid HormoneVitamin DVitaminsand side effectbiomarkerboneSGLT2 inhibitorvitamin D

Identifiers

PMID37738423
PMCPMC10795897
OpenAlexW4386951292

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

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.