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

NCT07225465 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 235/251U01DK143330-01
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 4

Brief 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

Keywords

Ketosis; Dapagliflozin; Type 1 Diabetes; Dual Glucose and Ketone Monitor; SGLT2 inhibitor

Outcome Measures

Primary Outcomes (2)

• Percent time spent with interstitial ketones ≥3.0mmol/L (Main Study)

  Percent of time spent with interstitial ketone levels ≥3.0mmol/L on dual glucose / ketone monitoring device during 12-weeks of taking Dapagliflozin

  Commencement to end of study (12 weeks)

• Percent of time spent with interstitial ketones ≥3.0mmol/L during exercise (Exercise Study)

  Percent of time spent with interstitial ketones ≥3.0mmol/L on dual glucose / ketone monitoring device from start of exercise to 12 hours post-commencement of exercise

  Weeks 4 to12

Secondary Outcomes (19)

• Percent of time with ketone levels in different ranges

  Commencement to end of study (12 weeks)

• Mean interstitial ketone levels

  Commencement to end of study (12 weeks)

• Incidence of diabetic ketoacidosis (DKA)

  Commencement to end of study (12 weeks)

• Change in HbA1c

  Week 0 and Week 12 from study commencement

• CGM metrics

  Commencement to end of study (12 weeks)

Other Outcomes (4)

• Percent time of sensor wear

  Commencement to end of study (12 weeks)

• Incidence of sensor- related skin infections

  Commencement to end of study (12 weeks)

• Mean duration of sensor survival before replacement

  Commencement to end of study (12 weeks)

Study Arms (2)

Dual glucose and ketone (DGK) sensor threshold 1.0mmol/L

ACTIVE COMPARATOR

The DGK will be set with threshold alarms activated at 1.0mmol/L for participant response to ketosis

Drug: FORXIGA

Dual glucose and ketone (DGK) sensor threshold 1.5mmol/L

ACTIVE COMPARATOR

The DGK will be set with threshold alarms activated at 1.5mmol/L for participant response to ketosis

Drug: FORXIGA

Interventions

FORXIGA DRUG

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

Dual glucose and ketone (DGK) sensor threshold 1.0mmol/L; Dual glucose and ketone (DGK) sensor threshold 1.5mmol/L

Eligibility Criteria

• Age: 24 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 24 and 85 years of age inclusive (66% 24Y to 65Y; and 33% \>65Y to 85Y)
• Diagnosed with T1D (made on clinical criteria) for at least 1 year
• Insulin regimen either on MDI or insulin pump with at least 40% in one mode
• Minimum total daily insulin dose 0.4 Units per kg / day (can be on insulin pump or MDI);
• HbA1c \<10% (86mmol/ mol)
• Minimum daily carbohydrate intake of 100g
• Willing to adhere to the study protocol
• Ability to perform high-intensity exercise (specific to the exercise sub-study)

You may not qualify if:

• Pregnancy or planned pregnancy
• eGFR \<30ml/min/1.73m2
• History of DKA in the last 12 months
• Use of low carbohydrate diet (\<100g/day)
• Diabetic gastroparesis
• Tape allergy
• Heavy alcohol use (15 standard drinks per week or binge drinking)
• Use of SGLT inhibitor in the last month
• Medications increasing the risk of DKA e.g. steroids, anorectic agents (eg phentermine, naltrexone HCl/bupropion HCl, and GLP 1 agonists).
• Major medical or psychiatric illness that in the opinion of the investigator would interfere with protocol adherence or impact participant safety.

Sponsors & Collaborators

• St Vincent's Hospital Melbourne: lead
• Baker Heart and Diabetes Institute: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• University of Melbourne: collaborator
• Melbourne Health: collaborator
• Austin Health: collaborator

Study Sites (4)

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Baker Heart and Diabetes Institute

Melbourne, Victoria, 3004, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Ketosis

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Acidosis; Acid-Base Imbalance

Central Study Contacts

Prof. David O'Neal

CONTACT

+61 3 9231 2757; DTRG-t1research@unimelb.edu.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinating Principal Investigator

Study Record Dates

• First Submitted: November 2, 2025
• First Posted: November 6, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: November 6, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)