Evaluating Safe Ketone Thresholds To Minimise Ketosis in People With Type 1 Diabetes Using Dapagliflozin

Summary

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a type of medicine that help the kidneys get rid of extra sugar in the blood through urine. In people with type 2 diabetes (T2D), these medications help lower blood sugar levels, help people lose weight and improve heart and kidney health.

SGLT2 inhibitors are mainly used in T2D, however some studies show they might also help people with type 1 diabetes (T1D). The same health benefits observed in people with T2D the investigators anticipate may help those with T1D. Currently, there is a safety concern that people with T1D using these medicines can raise the risk of diabetic ketoacidosis (DKA). DKA occurs when the body doesn't have enough insulin (a hormone made in the pancreas that helps your body use sugar (glucose) for energy), it starts to break down fats as a source of energy. This breakdown of fats produces ketones. Very high levels of ketones in the blood can make the blood acidic (toxic) and lead to DKA. If not treated in time, this can make the person living with T1D very ill and can be life-threatening. Because of this risk, health agencies like the FDA in the U.S., and the TGA in Australia have not approved use of SGLT2 inhibitors for people with T1D.

Still, some experts believe SGLT2 inhibitors may safely be used alongside insulin in T1D if DKA risk is carefully managed. This might be possible with early detection and treatment of rising ketone levels. One approach is using continuous ketone monitors, which track ketone levels in real time and can alert users early. People would also need proper education on what to do if ketone levels start rising.

To date, there's no official agreement on the exact ketone level that should trigger action. Some suggest action when ketone levels reach 1.0 or 1.5 mmol/L. A lower limit like 1.0 mmol/L may be safer, but it could also lead to too many alarms and extra stress, or unnecessary eating to bring ketones down.

Therefore, the aim of this study is to assess if initiating responses to elevated ketone levels at a threshold of 1.0 mmol/L, compared to a threshold of 1.5 mmol/L, will reduce the risk of DKA in people with T1D using Dapagliflozin.

The investigators will recruit 115 adults with T1D and provide Dapagliflozin (SGLT2 inhibitor) and continuous glucose and ketone monitoring (DGK) devices. Participants will be randomly assigned to two groups. Group 1 will wear a DGK with alarms set at ketone level of 1.0 mmol/L and receive education about taking action when ketone levels are ≥1.0 mmol/L. Group 2 will wear a DGK with alarms set at ketone level of 1.5 mmol/L and receive education about taking action when ketone levels are ≥1.5 mmol/L. Participants will be assessed for time spent with critically high ketone levels, incidence of DKA, glucose and person reported outcomes.

Findings from this study will provide real life data and clinical evidence to help guide safe use of SGLT2 inhibitors in people with T1D by informing protocols for monitoring and managing associated DKA risks.

Conditions

• Type 1 Diabetes Mellitus

Interventions

DRUG

FORXIGA

All participants will take FORXIGA (Dapagliflozin) orally at a dose of 10mg/day for 12 weeks

Sponsors & Collaborators

• Baker Heart and Diabetes Institute

  collaborator OTHER

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• University of Melbourne

  collaborator OTHER

• Melbourne Health

  collaborator OTHER

• Austin Health

  collaborator OTHER_GOV

• St Vincent's Hospital Melbourne

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

24 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-02-28

Primary Completion

2028-02-29

Completion

2028-02-29

Countries

• Australia

Study Locations