Trial reportJCI insight2018
Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study.
Trial report in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02891954. Cited by 101 papers, 6 of them syntheses that pooled 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.
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.
Pharmacogenomics to Predict Responses to SGLT2 Inhibitors
Acute Effects of Canagliflozin, a Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitor on Bone Metabolism in Healthy Volunteers
Who cites it
101 citing papers in PubMed, 6 syntheses or guidelines pooled it, 160 citations in OpenAlex.
- Comparative effectiveness and safety of sodium-glucose cotransporter 2 inhibitors vs glucagon-like peptide 1 receptor agonists in elderly patients with type 2 diabetes mellitus: a meta-analysis.Frontiers in endocrinology · 2025Pooled it
- A comprehensive meta-analysis on the association of SGLT2is and GLP-1RAs with vascular diseases, digestive diseases and fractures.Acta diabetologica · 2024Pooled it
- Effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation on offspring outcomes: a systematic review of the evidence.Frontiers in endocrinology · 2023Pooled it
- Comparative safety of different recommended doses of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.Frontiers in endocrinology · 2023 · on this mapPooled it
- [Diagnosis and management of patients with diabetes and co-existing osteoporosis (Update 2023) : Common guideline of the Austrian Society for Bone and Mineral Research and the Austrian Diabetes Society].Wiener klinische Wochenschrift · 2023Guideline
- The Extraglycemic Effect of SGLT-2is on Mineral and Bone Metabolism and Bone Fracture.Frontiers in endocrinology · 2022Pooled it
- Effects of Dapagliflozin on the Bone of Patients with CKD on Dialysis.Calcified tissue international · 2026Trial
- Impact of SGLT2i on bone health in patients with lupus nephritis: randomized double blinded placebo-controlled clinical trial.Journal of nephrology · 2025Trial
- Effects of dapagliflozin on sodium excretion, blood pressure and volume status in patients with type 2 diabetes and/or chronic kidney disease: The DAPASALT trial.Diabetes, obesity & metabolism · 2025Trial
- Fasting and postprandial kidney haemodynamic effects of empagliflozin and linagliptin in mono- and combination therapy compared to gliclazide in overweight people with type 2 diabetes (RACELINES): A randomised, double-blind trial.Diabetes, obesity & metabolism · 2025Trial
- Effects of dapagliflozin on volume status and systemic haemodynamics in patients with chronic kidney disease without diabetes: Results from DAPASALT and DIAMOND.Diabetes, obesity & metabolism · 2022Trial
- Trial
- Effect of dapagliflozin on mineral homeostasis in patients with type 2 diabetes: A real-world retrospective cohort study.Journal of Taibah University Medical Sciences · 2026Article
- SGLT2 Inhibitors: Dual Effects on Erythropoiesis and Bone Metabolism.Journal of bone metabolism · 2026Review
- Phosphate homeostasis and apparent treatment-resistant hypertension in chronic kidney disease: the Chronic Renal Insufficiency Cohort (CRIC) study.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- SGLT2i, anti-endothelin A and double endothelin and angiotensin inhibitors: a new future for chronic kidney disease in children.Pediatric nephrology (Berlin, Germany) · 2026Review
- Genetics of Response to Canagliflozin (GRC) Study: Rationale, Design, and Pharmacodynamic Responses.Clinical and translational science · 2026Article
- SGLT2 inhibitors for kidney protection in children: expanding horizons beyond endocrinology.Pediatric nephrology (Berlin, Germany) · 2026Review
- A Western Diet High in Phosphate Primes the Development of the CKD-Mineral Bone Disorder in an Alport Syndrome Model.Kidney360 · 2026Article
- The effects of elevated phosphate on the kidney - damaging the gatekeeper.Pflugers Archiv : European journal of physiology · 2026Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundSodium glucose cotransporter-2 (SGLT2) inhibitors are the most recently approved class of drugs for type 2 diabetes and provide both glycemic efficacy and cardiovascular risk reduction. A number of safety issues have been identified, including treatment-emergent bone fractures. To understand the overall clinical profile, these safety issues must be balanced against an attractive efficacy profile. Our study was designed to investigate pathophysiological mechanisms mediating treatment-emergent adverse effects on bone health.
methodsWe conducted a single-blind randomized crossover study in hospitalized healthy adults (n = 25) receiving either canagliflozin (300 mg/d) or placebo for 5 days. The primary end-point was the drug-induced change in AUC for plasma intact fibroblast growth factor 23 (FGF23) immunoactivity between 24 and 72 hours.
resultsCanagliflozin administration increased placebo-subtracted mean levels of serum phosphorus (+16%), plasma FGF23 (+20%), and plasma parathyroid hormone (PTH) (+25%), while decreasing the level of 1,25-dihydroxyvitamin D (-10%). There was substantial interindividual variation in the magnitude of each of these pharmacodynamic responses. The increase in plasma FGF23 was correlated with the increase in serum phosphorus, and the decrease in plasma 1,25-dihydroxyvitamin D was correlated with the increase in plasma FGF23.
conclusionsCanagliflozin induced a prompt increase in serum phosphorus, which triggers downstream changes in FGF23, 1,25-dihydroxyvitamin D, and PTH, with potential to exert adverse effects on bone health. These pharmacodynamic data provide a foundation for future research to elucidate pathophysiological mechanisms of adverse effects on bone health, with the objective of devising therapeutic strategies to mitigate the drug-associated fracture risk.
trial registrationClinicalTrial.gov (NCT02404870).
fundingSupported by the Intramural Program of NIDDK.
Indexed as
Identifiers
What Socratic holds
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.