Diabetic Ketoacidosis From New SGLT2i: Can Genomics Estimate Risk

NCT ID: NCT05402579

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 63 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-07-29
• Study Completion Date: 2025-01-20

Brief 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. 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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: OTHER

Study Groups

Cases

Patients with type 2 diabetes mellitus who were hospitalized with SGLT2 inhibitor-associated DKA (60 cases).

Genomic analysis

Intervention Type: GENETIC

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)

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).

Genomic analysis

Intervention Type: GENETIC

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)

Interventions

Genomic analysis

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)

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

To be considered eligible for participation in this study, a participant must meet each of the following criteria:

1. Be 18 years or older and have a diagnosis of type 2 diabetes mellitus.

2. Have been admitted to hospital with SGLT2 inhibitor-associated DKA (cases) or admitted to hospital on an SGLT2 inhibitor and not have DKA (controls).

3. Be able to provide written consent (or, if patient is unable, have a substitute decision maker [SDM] available).

Exclusion Criteria

A participant will be ineligible for participation in this study if he or she satisfies any one or more of the following criteria:

1. Diagnosis of type 1 diabetes mellitus.

2. Unable to spit 10mL into a vial.

3. A first degree relative has already been recruited into the study.

4. Had an alcohol binge before admission

5. Had prolonged fasting (>48 hours) prior to hospital admission

6. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Unity Health Toronto

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: collaborator

Sault Area Hospital

OTHER

Sponsor Role: collaborator

Mount Sinai Hospital, Canada

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

St. Joseph's Health Centre (Unity Health Toronto)

Toronto, Ontario, Canada

Toronto General Hospital (University Health Network)

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

CTO 3737

Identifier Type: -

Identifier Source: org_study_id