Diabetes Type 2DaNGERNCT05402579
Diabetic Ketoacidosis From New SGLT2i: Can Genomics Estimate Risk
An observational study of Diabetes Type 2 and DKA, run by Mount Sinai Hospital, Canada at 2 sites in Canada.
Trial summary
Sodium glucose co-transporter 2 (SGLT2) inhibitors have revolutionized care for people living with type 2 diabetes mellitus (T2DM). They reduce a person's risk of heart failure, renal failure, myocardial infarction, stroke, cardiovascular mortality, and potentially all-cause mortality. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Diabetes Type 2, DKA, Diabetic Ketoacidosis
- What is being tested?
- Genomic analysis
- How many people
- 63 participants
- Where
- 2 sitesCanada
- Study dates
- 29 Jul 2022to 20 Jan 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Cases: Patients with type 2 diabetes mellitus who were hospitalized with SGLT2 inhibitor-associated DKA will be eligible for inclusion in our study. Controls: There are two sources for controls. [1] Patients hospitalized at one of the participating hospitals who were on an SGLT2i and do not have DKA. [2] Population controls using publicly available data from the Canadian Longitudinal Study on Aging (CLSA) database.
Who may be able to join
- To be considered eligible for participation in this study, a participant must meet each of the following criteria:
- Be 18 years or older and have a diagnosis of type 2 diabetes mellitus.
- Have been admitted to hospital with SGLT2 inhibitor-associated DKA (cases) or admitted to hospital on an SGLT2 inhibitor and not have DKA (controls).
- Be able to provide written consent (or, if patient is unable, have a substitute decision maker [SDM] available).
Who cannot join
- A participant will be ineligible for participation in this study if he or she satisfies any one or more of the following criteria:
- Diagnosis of type 1 diabetes mellitus.
- Unable to spit 10mL into a vial.
- A first degree relative has already been recruited into the study.
- Had an alcohol binge before admission
- Had prolonged fasting (>48 hours) prior to hospital admission
- Recently stopped their insulin (within the past 7 days prior to hospital admission)
- Our study will not include children or pregnant women because SGLT2 inhibitors are not approved for use in either patient population.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
St. Joseph's Health Centre (Unity Health Toronto)
Toronto, Ontario
Toronto General Hospital (University Health Network)
Toronto, Ontario
About this study
Official title: Diabetic Ketoacidosis From New SGLT2i: Can Genomics Estimate Risk (DaNGER)
Sodium glucose co-transporter 2 (SGLT2) inhibitors have revolutionized care for people living with type 2 diabetes mellitus (T2DM). They reduce a person's risk of heart failure, renal failure, myocardial infarction, stroke, cardiovascular mortality, and potentially all-cause mortality. Remarkably, some of these benefits also extend to people who do not have T2DM. While the benefits of SGLT2 inhibitors are impressive, there is one life-threatening side effect associated with their use: diabetic ketoacidosis (DKA). The ability to predict which patients are at highest risk of DKA is needed to sufficiently mitigate this risk. Moreover, considering the impressive benefits of SGLT2 inhibitors, identifying patients at the lowest risk of SGLT2 inhibitor-associated DKA is also important so that providers do not overestimate risk in those who stand to benefit most.
Advances in genomic technologies and related analyses have provided unprecedented opportunities to bring genomics-driven precision medicine initiatives to the forefront of clinical research. Leading these developments has been the progress made by genome-wide association studies (GWAS) due to decreasing genotyping costs, and consequently, the ability to routinely study large numbers of patients. These approaches allow for systematic screening of the genome in an unbiased manner and have accelerated the discovery of genetic variants and novel biological processes that contribute to the development of adverse treatment outcomes.
By using innovative approaches, which harness large cohorts of population controls, sample size limitations that are associated with rare adverse drug reactions such as SGLT2 inhibitor-associated DKA can be overcome. The DANGER study represents a highly innovative new direction wherein partnership among basic science researchers and computational biologists will lead to the application of genomic techniques to identify genetic variants that may be associated with SGLT2 inhibitor-associated DKA.
- Conditions
- Diabetes Type 2, DKA, Diabetic Ketoacidosis
- Being tested
- Genomic analysis
- Keywords
- DKA, SGLT2i, Diabetes Type 2
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetic Ketoacidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genomic analysisGenetic
Genetic samples will be collected using a DNA saliva collection kit (Oragene: OG-510) and will be sent for genome-wide genotyping to The Centre for Applied Genomics in The Hospital for Sick Children (SickKids)
| Study group | Role | What they receive |
|---|---|---|
| Cases | Patients with type 2 diabetes mellitus who were hospitalized with SGLT2 inhibitor-associated DKA (60 cases). Receives: Genetic: Genomic analysis | |
| Controls | There are two sources for controls. [1] Patients hospitalized at one of the participating hospitals who were on an SGLT2i and do not have DKA. [2] Population controls using publicly available data from the Canadian Longitudinal Study on Aging (CLSA) database (1000 controls via CLSA). Receives: Genetic: Genomic analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of genomic variants associated with an increased risk of SGLT2 inhibitor-associated DKA
Genetic ancestry will be calculated using principal component analyses and outliers will be removed. GWAS will be performed with SAIGE, including genetic ancestry and the relevant clinical/demographic variables as covariates, to identify genetic variants associated with SGLT2 inhibitor-associated DKA.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2022
- Study start29 Jul 2022
- Primary completion20 Jan 2025
- Study completion20 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- Collaborators
- Unity Health Toronto, University Health Network, Toronto, Sault Area Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05402579
- Sponsor's protocol ID
- CTO 3737
- Acronym
- DaNGER
- Status last verified
- Nov 2024
- First submitted
- 30 May 2022
- Last updated
- 4 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diabetic Ketoacidosis From New SGLT2i: Can Genomics Estimate Risk (DaNGER)
- ClinicalTrials.gov ID
- NCT05402579
- Acronym / sponsor ID
- DaNGER / CTO 3737
- Conditions
- Diabetes Type 2, DKA, Diabetic Ketoacidosis
- Keywords
- DKA, SGLT2i, Diabetes Type 2
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Mount Sinai Hospital, CanadaUniversity, hospital or other
- Collaborators
- Unity Health Toronto, University Health Network, Toronto, Sault Area Hospital
- Study start
- 29 Jul 2022 (actual)
- Primary completion
- 20 Jan 2025 (actual)
- Study completion
- 20 Jan 2025 (actual)
- First posted
- 2 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sodium glucose co-transporter 2 (SGLT2) inhibitors have revolutionized care for people living with type 2 diabetes mellitus (T2DM). They reduce a person's risk of heart failure, renal failure, myocardial infarction, stroke, cardiovascular mortality, and potentially all-cause mortality. Remarkably, some of these benefits also extend to people who do not have T2DM. While the benefits of SGLT2 inhibitors are impressive, there is one life-threatening side effect associated with their use: diabetic ketoacidosis (DKA). The ability to predict which patients are at highest risk of DKA is needed to sufficiently mitigate this risk. Moreover, considering the impressive benefits of SGLT2 inhibitors, identifying patients at the lowest risk of SGLT2 inhibitor-associated DKA is also important so that providers do not overestimate risk in those who stand to benefit most.
Advances in genomic technologies and related analyses have provided unprecedented opportunities to bring genomics-driven precision medicine initiatives to the forefront of clinical research. Leading these developments has been the progress made by genome-wide association studies (GWAS) due to decreasing genotyping costs, and consequently, the ability to routinely study large numbers of patients. These approaches allow for systematic screening of the genome in an unbiased manner and have accelerated the discovery of genetic variants and novel biological processes that contribute to the development of adverse treatment outcomes.
By using innovative approaches, which harness large cohorts of population controls, sample size limitations that are associated with rare adverse drug reactions such as SGLT2 inhibitor-associated DKA can be overcome. The DANGER study represents a highly innovative new direction wherein partnership among basic science researchers and computational biologists will lead to the application of genomic techniques to identify genetic variants that may be associated with SGLT2 inhibitor-associated DKA.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cases | – | Genetic: Genomic analysisPatients with type 2 diabetes mellitus who were hospitalized with SGLT2 inhibitor-associated DKA (60 cases). |
| Controls | – | Genetic: Genomic analysisThere are two sources for controls. [1] Patients hospitalized at one of the participating hospitals who were on an SGLT2i and do not have DKA. [2] Population controls using publicly available data from the Canadian Longitudinal Study on Aging (CLSA) database (1000 controls via CLSA). |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Cases: Patients with type 2 diabetes mellitus who were hospitalized with SGLT2 inhibitor-associated DKA will be eligible for inclusion in our study. Controls: There are two sources for controls. [1] Patients hospitalized at one of the participating hospitals who were on an SGLT2i and do not have DKA. [2] Population controls using publicly available data from the Canadian Longitudinal Study on Aging (CLSA) database.
Key inclusion criteria (4 listed)
- To be considered eligible for participation in this study, a participant must meet each of the following criteria:
- Be 18 years or older and have a diagnosis of type 2 diabetes mellitus.
- Have been admitted to hospital with SGLT2 inhibitor-associated DKA (cases) or admitted to hospital on an SGLT2 inhibitor and not have DKA (controls).
- Be able to provide written consent (or, if patient is unable, have a substitute decision maker [SDM] available).
Key exclusion criteria (8 listed)
- A participant will be ineligible for participation in this study if he or she satisfies any one or more of the following criteria:
- Diagnosis of type 1 diabetes mellitus.
- Unable to spit 10mL into a vial.
- A first degree relative has already been recruited into the study.
- Had an alcohol binge before admission
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genomic analysisGenetic samples will be collected using a DNA saliva collection kit (Oragene: OG-510) and will be sent for genome-wide genotyping to The Centre for Applied Genomics in The Hospital for Sick Children (SickKids) | Genetic | Cases, Controls |
Primary outcome
Identification of genomic variants associated with an increased risk of SGLT2 inhibitor-associated DKA
Time frame: One year
Genetic ancestry will be calculated using principal component analyses and outliers will be removed. GWAS will be performed with SAIGE, including genetic ancestry and the relevant clinical/demographic variables as covariates, to identify genetic variants associated with SGLT2 inhibitor-associated DKA.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Type 2 and DKA, run by Mount Sinai Hospital, Canada at 2 sites in Canada.
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 4 inclusion and 8 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: finished, as of the sponsor's last update on 4 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Identification of genomic variants associated with an increased risk of SGLT2 inhibitor-associated DKA (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Dec 2025.