Evidence map›Paper›PMID 26580237›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2016

Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus.

Nelson B Watts, John P Bilezikian, Keith Usiskin, Robert Edwards, Mehul Desai, Gordon Law, Gary Meininger

Open access · bronzeAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers, 14 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
203citing papers in PubMed, 14 pooled it
38.7field-weighted citation impact, top 1% 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.

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

203 citing papers in PubMed, 14 syntheses or guidelines pooled it, 443 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Effect of SGLT2 inhibitors on fractures, BMD, and bone metabolism markers in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023
    Pooled it
  4. Pooled it
  5. Guideline
  6. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022
    Guideline
  7. Pooled it
  8. Influence of glycemic control and hypoglycemia on the risk of fracture in patients with diabetes mellitus: a systematic review and meta-analysis of observational studies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021
    Pooled it
  9. Pooled it
  10. Risk of fracture with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in real-world use: systematic review and meta-analysis of observational studies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2019
    Pooled it
  11. Treatment of Diabetes in Older Adults: An Endocrine Society* Clinical Practice Guideline.The Journal of clinical endocrinology and metabolism · 2019
    Guideline
  12. Pooled it
  13. Fracture Risk After Initiation of Use of Canagliflozin: A Cohort Study.Annals of internal medicine · 2019 · on this map
    Pooled it
  14. Pooled it
  15. Trial
  16. Trial
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143 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Nelson B WattsMercy Health Osteoporosis and Bone Health Services Clinical Trial Center (N.B.W.), Cincinnati, Ohio 45236; Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; and Janssen Research & Development, LLC (K.U., R.E., M.D., G.L., G.M.), Raritan, New Jersey 08869.
John P BilezikianMercy Health Osteoporosis and Bone Health Services Clinical Trial Center (N.B.W.), Cincinnati, Ohio 45236; Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; and Janssen Research & Development, LLC (K.U., R.E., M.D., G.L., G.M.), Raritan, New Jersey 08869.
Keith UsiskinMercy Health Osteoporosis and Bone Health Services Clinical Trial Center (N.B.W.), Cincinnati, Ohio 45236; Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; and Janssen Research & Development, LLC (K.U., R.E., M.D., G.L., G.M.), Raritan, New Jersey 08869.
Robert EdwardsMercy Health Osteoporosis and Bone Health Services Clinical Trial Center (N.B.W.), Cincinnati, Ohio 45236; Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; and Janssen Research & Development, LLC (K.U., R.E., M.D., G.L., G.M.), Raritan, New Jersey 08869.
Mehul DesaiMercy Health Osteoporosis and Bone Health Services Clinical Trial Center (N.B.W.), Cincinnati, Ohio 45236; Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; and Janssen Research & Development, LLC (K.U., R.E., M.D., G.L., G.M.), Raritan, New Jersey 08869.
Gordon LawMercy Health Osteoporosis and Bone Health Services Clinical Trial Center (N.B.W.), Cincinnati, Ohio 45236; Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; and Janssen Research & Development, LLC (K.U., R.E., M.D., G.L., G.M.), Raritan, New Jersey 08869.
Gary MeiningerMercy Health Osteoporosis and Bone Health Services Clinical Trial Center (N.B.W.), Cincinnati, Ohio 45236; Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; and Janssen Research & Development, LLC (K.U., R.E., M.D., G.L., G.M.), Raritan, New Jersey 08869.
Janssen (United States) · USColumbia University · USMercy Health · US

Funding

Training Program in Cancer TherapeuticsT32CA117846 · NCI · UNIVERSITY OF CINCINNATI · PI PRICE, CAROLYN M, TAKIAR, VINITA · 2006 to 2022
$6.5M
NCI NIH HHS T32 CA117846
6 · The paper itself

Abstract

contextCanagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM).

objectiveThe purpose of this study was to describe the effects of canagliflozin on bone fracture risk. DESIGN AND

settingThis was a randomized phase 3 study in patients with T2DM. PATIENTS AND

interventionsCanagliflozin doses of 100 and 300 mg were evaluated in the overall population of patients from 9 placebo- and active-controlled studies (N = 10 194), as well as in separate analyses of a single trial enriched with patients with a prior history/risk of cardiovascular disease (ie, the CANagliflozin cardioVascular Assessment Study [CANVAS]; N = 4327) and a pooled population of 8 non-CANVAS studies (N = 5867). OUTCOME MEASURES: The incidence of adjudicated fracture adverse events (AEs), fall-related AEs, and volume depletion-related AEs was assessed.

resultsThe incidence of fractures was similar with canagliflozin (1.7%) and noncanagliflozin (1.5%) in the pooled non-CANVAS studies. In CANVAS, a significant increase in fractures was seen with canagliflozin (4.0%) vs placebo (2.6%) that was balanced between the upper and lower limbs. The incidence of fractures was higher with canagliflozin (2.7%) vs noncanagliflozin (1.9%) in the overall population, which was driven by the increase of fractures in CANVAS. The incidence of reported fall-related AEs was low, but significantly higher with canagliflozin in CANVAS, potentially related to volume depletion-related AEs, but not significantly different in the pooled non-CANVAS studies and the overall population.

conclusionsFracture risk was increased with canagliflozin treatment, driven by CANVAS patients, who were older, with a prior history/risk of cardiovascular disease, and with lower baseline estimated glomerular filtration rate and higher baseline diuretic use. The increase in fractures may be mediated by falls; however, the cause of increased fracture risk with canagliflozin is unknown.

Indexed as

Accidental FallsAdultAgedAged, 80 and overAge FactorsCanagliflozinCardiovascular DiseasesDiabetes Mellitus, Type 2DiureticsDose-Response Relationship, DrugDouble-Blind MethodFemaleFractures, BoneHumansHypoglycemic AgentsIncidenceCanagliflozinDiureticsHypoglycemic Agents

Identifiers

PMID26580237
PMCPMC4701850
OpenAlexW2179831365

What OpenQuestion holds

Texttitle and abstract
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.