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Diabetes Mellitus, Type 2Phase 1NCT02891954

Genetics of Response to Canagliflozin

A Phase 1 study testing Canagliflozin in people with Diabetes Mellitus, Type 2, run by University of Maryland, Baltimore.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Five daily doses of canagliflozin (300 mg) will be administered to healthy volunteers. Pharmacodynamic responses to canagliflozin will be assessed both at 2 days and 6 days after administration of the first dose of canagliflozin. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
Canagliflozin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
700 participants
Where
No sites listed yet
Study dates
Sep 2016to 25 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Of Amish descent
  • Age 18 or older
  • BMI: 18-40 kg/m2

Who cannot join

  • Known allergy to canagliflozin
  • History of diabetes, random glucose greater than 200 mg/dL, or HbA1c greater than or equal to 6.5%
  • Currently taking diuretics, antihypertensive medication uric acid lowering medications, or other medication that the investigator judges will make interpretation of the results difficult
  • Significant debilitating chronic cardiac, hepatic, pulmonary, or renal disease or other diseases that the investigator judges will make interpretation of the results difficult or increase the risk of participation
  • Seizure disorder
  • Unwilling to go off of vitamin supplements and over the counter medication (except for acetaminophen) for at least two weeks prior to the first home visit and agree to avoid these medications for the duration of the study.
Show all 12Show fewer
  • Positive urine human chorionic gonadotropin test or known pregnancy within 3 months of the start of the study
  • Estimated glomerular filtration rate less than 60 mL/min
  • Currently breast feeding or breast feeding within 3 month of the start of the study
  • Liver function tests greater than 2 times the upper limit of normal
  • Hematocrit less than 35%
  • Abnormal thyroid hormone stimulating hormone

About this study

Official title: Pharmacogenomics to Predict Responses to SGLT2 Inhibitors

Five daily doses of canagliflozin (300 mg) will be administered to healthy volunteers. Pharmacodynamic responses to canagliflozin will be assessed both at 2 days and 6 days after administration of the first dose of canagliflozin. A genome-wide association study (GWAS) will be conducted to search for genetic variants that are associated with each of the pharmacodynamic responses to canagliflozin.

Read the detailed description

After obtaining informed consent, healthy Amish research subjects will be screened for eligibility. Immediately after obtaining blood samples for baseline clinical chemistry tests wills, patients will initiate 5 days of canagliflozin (300 mg) treatment. Fasting blood samples will be obtained to assess pharmacodynamic responses at both 48 hours and 120 hours after initiating canagliflozin. The principal pharmacodynamic responses will include 24 hour urinary excretion of glucose, serum chemistries (phosphorus, FGF23, 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), glucagon, beta-hydroxybutyrate, acetoacetate, procollagen type I N-terminal peptide (P1NP), and beta-CTX). Research subjects will undergo genotyping, and a genome-wide association study will be conducted to search for genetic variants that are associated with pharmacodynamic responses to canagliflozin.

Being tested
Canagliflozin
Keywords
Glucosuria, SGLT2 inhibitors, Canagliflozin, FGF23, Parathyroid hormone, 1,25-Dihydroxyvitamin D, Glucagon, Ketone bodies, Uric acid, Pharmacogenomics
Medical subject headings
Diabetes Mellitus, Type 2, Glycosuria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CanagliflozinDrug

    Also called Invokana (brand name for canagliflozin)

    Healthy volunteers will receive canagliflozin (300 mg per day) in the morning for five days.

Study groups in NCT02891954
Study groupRoleWhat they receive
Single armExperimentalHealthy volunteers will receive canagliflozin to assess pharmacodynamic responses to drug.
Receives: Drug: Canagliflozin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Urinary glucose excretion (during the time interval 24-48 hours after first administration of canagliflozin)

    Urine collection will be initiated 24 hours after initiation of canagliflozin treatment, and continued for an additional 24 hours.

    Measured: 24-48 hours

Secondary outcomes (6)

  1. Bone-related biomarkers

    Serum phosphorus, FGF23, 1,25-dihydroxyvitamin D, PTH, P1NP, and beta-CTX

    Measured: 48 hrs

  2. Bone-related biomarkers

    Serum phosphorus, FGF23, 1,25-dihydroxyvitamin D, PTH, P1NP, and beta-CTX

    Measured: 120 hrs

  3. Ketosis-related biomarkers

    glucagon, acetoacetate, beta-hydroxybutyrate

    Measured: 48 hrs

  4. Ketosis-related biomarkers

    glucagon, acetoacetate, beta-hydroxybutyrate

    Measured: 120 hurs

  5. Serum uric acid

    Change in serum uric acid at 48 hours

    Measured: 48 hrs

  6. Serum uric acid

    Change in serum uric acid at 120 hours

    Measured: 120 hrs

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2016 (estimated)
  2. Study startSep 2016
  3. Primary completion25 Sep 2023
  4. Study completion25 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
700 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02891954
Sponsor's protocol ID
HP-00069977
Other IDs
R01DK118942
Status last verified
Dec 2025
First submitted
30 Aug 2016
Last updated
18 Dec 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Taylor SI, Blau JE, Rother KI. Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. 2015 Jan;3(1):8-10. doi: 10.1016/S2213-8587(14)70227-X. Epub 2014 Dec 16. No abstract available.

    PubMed 25523498

  • Taylor SI, Blau JE, Rother KI. SGLT2 Inhibitors May Predispose to Ketoacidosis. J Clin Endocrinol Metab. 2015 Aug;100(8):2849-52. doi: 10.1210/jc.2015-1884. Epub 2015 Jun 18.

    PubMed 26086329

  • Blau JE, Bauman V, Conway EM, Piaggi P, Walter MF, Wright EC, Bernstein S, Courville AB, Collins MT, Rother KI, Taylor SI. Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study. JCI Insight. 2018 Apr 19;3(8):e99123. doi: 10.1172/jci.insight.99123. eCollection 2018 Apr 19.

    PubMed 29669938

  • Blau JE, Taylor SI. Adverse effects of SGLT2 inhibitors on bone health. Nat Rev Nephrol. 2018 Aug;14(8):473-474. doi: 10.1038/s41581-018-0028-0.

    PubMed 29875481

  • Beitelshees AL, Leslie BR, Taylor SI. Sodium-Glucose Cotransporter 2 Inhibitors: A Case Study in Translational Research. Diabetes. 2019 Jun;68(6):1109-1120. doi: 10.2337/dbi18-0006.

    PubMed 31109940

  • Shahidzadeh Yazdi Z, Streeten EA, Whitlatch HB, Montasser ME, Beitelshees AL, Taylor SI. Vitamin D Deficiency Increases Vulnerability to Canagliflozin-induced Adverse Effects on 1,25-Dihydroxyvitamin D and PTH. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e646-e656. doi: 10.1210/clinem/dgad554.

    PubMed 37738423

  • Shahidzadeh Yazdi Z, Streeten EA, Whitlatch HB, Montasser ME, Beitelshees AL, Taylor SI. Critical Role for 24-Hydroxylation in Homeostatic Regulation of Vitamin D Metabolism. J Clin Endocrinol Metab. 2025 Jan 21;110(2):e443-e455. doi: 10.1210/clinem/dgae156.

    PubMed 38481375

  • Shahidzadeh Yazdi Z, Streeten EA, Whitlatch HB, Bargal SA, Beitelshees AL, Taylor SI. Value of Vitamin D Metabolite Ratios in 3 Patients as Diagnostic Criteria to Assess Vitamin D Status. JCEM Case Rep. 2024 Jun 28;2(7):luae095. doi: 10.1210/jcemcr/luae095. eCollection 2024 Jul.

    PubMed 38947416

  • Zhang X, Wang Y, Wang H, Zhang X. Trends in Prevalence of Thyroid Dysfunction and its Associations With Mortality Among US Participants, 1988-2012. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e657-e666. doi: 10.1210/clinem/dgad558.

    PubMed 37738422

  • Taylor SI, Cherng HR, Shahidzadeh Yazdi Z, Montasser ME, Whitlatch HB, Mitchell BD, Shuldiner AR, Streeten EA, Beitelshees AL. Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker. Diabetes Obes Metab. 2023 Dec;25(12):3512-3520. doi: 10.1111/dom.15246. Epub 2023 Aug 22.

    PubMed 37608471

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Canagliflozin in people with Diabetes Mellitus, Type 2, run by University of Maryland, Baltimore.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Urinary glucose excretion (during the time interval 24-48 hours after first administration of canagliflozin) (time frame: 24-48 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02891954, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.

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