T2DPhase 2DIPPER PilotNCT07902726
Adding Acetazolamide on Top of SGLT2 Inhibition in Persons With Type 2 Diabetes
A Phase 2 study testing Acetazolamide 62.5 mg, Acetazolamide 125 mg and Acetazolamide 250 mg in people with T2D, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
The study aims to determine the acute efficacy and safety of three sequential doses of acetazolamide (62.5 mg, 125 mg, 250 mg) each for 2 weeks in 20 patients with T2D receiving background SGLT2i therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- T2D
- What is being tested?
- Acetazolamide 62.5 mg, Acetazolamide 125 mg and Acetazolamide 250 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 1 Dec 2026to 1 Dec 2028
- Phase
- Phase 2
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed and dated written informed consent.
- Adult (≥18 years) at the time of consent
- Established T2D diagnosis as per Diabetes Canada
- HbA1c ≤10.0%
- eGFR ≥45 ml/min/1.73m2
- BP ≤160/90 and ≥90/60 mmHg
- BMI 18.5-45.0 kg/m2
- On stable dose of maximally tolerated RAASi for ≥30 days
Who cannot join
- Established diagnosis of type 1 diabetes as per Diabetes Canada
- With known or suspected hypersensitivity or allergy to acetazolamide, dapagliflozin or related products
- Iodine intolerance
- Untreated urinary or genital tract infection
- Serum potassium <3.5 mmol/L
- Serum bicarbonate <22 mEq/L
Show all 14Show fewer
- Use of carbonic anhydrase inhibitor in the 30 days prior to screening
- Liver disease (hepatic cirrhosis, alcohol/drug abuse ≥3 months, or serum AST, ALT, or total bilirubin >3X the upper limit of normal)
- Severe glaucoma
- Acute coronary syndrome, stroke or transient ischemic attack within 30 days prior to screening
- Active pregnancy, breastfeeding or planning to become pregnant during study period
- Participation in another drug trial within 30 days of screening
- Patient not able to understand and comply with study requirements, based on Investigator's judgment.
- Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcome
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Luxcia Kugathasan contact
Canada1 site
Toronto General Hospital
Toronto, Ontario, M5G 2N2
Cheng Xu, 416-340-4800 ext. 8508, cheng.xu@uhn.ca
David Z.I Cherney, MD CM, PhD, FRCPC
About this study
Official title: Adding Acetazolamide on Top of SGLT2 Inhibition in Persons With Type 2 Diabetes ('DIPPER') Pilot Study
The study aims to determine the acute efficacy and safety of three sequential doses of acetazolamide (62.5 mg, 125 mg, 250 mg) each for 2 weeks in 20 patients with T2D receiving background SGLT2i therapy.
Read the detailed description
Chronic kidney disease (CKD) is a common complication of type 2 diabetes (T2D) and is associated with an increased risk of kidney failure, cardiovascular disease, and premature death. Although current standard-of-care therapies, including renin-angiotensin-aldosterone system inhibitors (RAASi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and non-steroidal mineralocorticoid receptor antagonists (nsMRA), slow CKD progression, patients continue to experience substantial residual risk of kidney function decline despite treatment. Hyperfiltration remains a central driver of CKD progression and represents an important therapeutic target. Acetazolamide is a carbonic anhydrase inhibitor that has been used clinically for decades and has been shown to reduce glomerular hyperfiltration by increasing distal sodium delivery. Previous studies have demonstrated that acetazolamide produces an acute, reversible reduction in glomerular filtration rate (GFR), although its effects in patients with T2D receiving background SGLT2i therapy have not been evaluated. The Adding AcetazolamIde on top of SGLT2 inhibition in Persons wtih Type 2 Diabetes (DIPPER) pilot study is a phase II, open-label, single-arm, dose-escalation trial evaluating acetazolamide added to background SGLT2i therapy for 16 weeks. The study will evaluate the effect of acetazolamide on glomerular hyperfiltration, as measured by the acute, reversible change in measured GFR following each treatment period. The investigators will also study other important markers such as GFR recovery during washout periods, albuminuria, blood pressure, body weight, body composition, and safety and tolerability. The results of this study will help determine whether adding acetazolamide to SGLT2i therapy safely enhances SGLT2 inhibition's effects on renal hemodynamics, supporting its further evaluation as a potential treatment strategy for patients with T2D.
- Conditions
- T2D
- Being tested
- Acetazolamide 62.5 mg, Acetazolamide 125 mg, Acetazolamide 250 mg, Dapagliflozin 10mg
- Keywords
- acetazolamide, SGLT2 inhibition, GFR dip, dose-finding
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetazolamide 62.5 mgDrug
Oral acetazolamide 62.5 mg twice daily for 2 weeks
Acetazolamide 125 mgDrug
Oral acetazolamide 125 mg twice daily for 2 weeks
Acetazolamide 250 mgDrug
Oral acetazolamide 250 mg twice daily for 2 weeks
Dapagliflozin 10mgDrug
Oral dapagliflozin 10 mg once daily for 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| Acetazolamide | Experimental | Patients will be up-titrated starting at acetazolamide 62.5 mg twice daily for 2 weeks, followed by a 2-week washout period. This sequence will be repeated with acetazolamide doses of 125 mg twice daily for 2 weeks and 250 mg twice daily for 2 weeks, with each treatment period followed by a 2-week washout period. Receives: Drug: Acetazolamide 62.5 mg; Drug: Acetazolamide 125 mg; Drug: Acetazolamide 250 mg; Drug: Dapagliflozin 10mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Iohexol Measured GFR
The primary outcome of this study is the absolute change in measured GFR during each 2-week course of acetazolamide, while on background dapagliflozin therapy. GFR will be measured using plasma clearance of the iohexol contrast agent. The initial "dip" in GFR was selected as the primary outcome as it provides an early and measurable indicator of the treatment effect on kidney physiology. A transient reduction in GFR is a known physiological response to both acetazolamide and SGLT2i, reflecting their effects on hyperfiltration. Assessing this early change allows evaluation of the immediate physiological response to combination therapy but also acts as an indicator of the potential longer-term renal benefits.
Measured: From baseline to the end of treatment at 16 weeks
Secondary outcomes (10)
Measured GFR Recovery
Measured GFR through iohexol clearance will be used to determine GFR recovery to baseline following each washout period.
Measured: From baseline to the end of treatment at 16 weeks
eGFR
Measured using spot urine and FMV urine collection for serum creatinine, standardized per 1.73m2 body surface area. And estimated using CKD-EPI 2021 equation.
Measured: From baseline to the end of treatment at 16 weeks
Urine Albumin-to-Creatinine (UACR)
UACR will be quantified by measuring albumin and creatinine excretion using the average of three FMV samples.
Measured: From baseline to the end of treatment at 16 weeks
Systolic Blood Pressure
Systolic blood pressure will be measured as per Hypertension Canada and assessed using an automated vital signs monitor (Connex Vital Signs Monitor, Welch Allyn).
Measured: From baseline to the end of treatment at 16 weeks.
Diastolic Blood Pressure
Diastolic blood pressure will be measured as per Hypertension Canada and assessed using an automated vital signs monitor (Connex Vital Signs Monitor, Welch Allyn).
Measured: From baseline to the end of treatment at 16 weeks
Change in Body Weight
Measured: From baseline to the end of treatment at 16 weeks
Mean Arterial Pressure
Mean blood pressure will be measured as per Hypertension Canada and assessed using an automated vital signs monitor (Connex Vital Signs Monitor, Welch Allyn).
Measured: From baseline to the end of treatment at 16 weeks
Percent Fat Mass
Bioimpedance analysis will be performed to determine percent body fat.
Measured: From baseline to the end of treatment at 16 weeks
Percent Extracellular Fluid
Bioimpedance analysis will be performed to determine the percent extracellular fluid.
Measured: From baseline to the end of treatment at 16 weeks
Percent Total Body Water
Bioimpedance analysis will be performed to determine percent total body water.
Measured: From baseline to the end of treatment at 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2026
- Study start1 Dec 2026 (estimated)
- Primary completion1 Dec 2028 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for T2DStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Z.I. Cherney, University Health Network, Toronto
- Investigators
- David Z.I Cherney, MD CM, PhD, FRCPC, Principal investigator, University Health Network, Toronto General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07902726
- Sponsor's protocol ID
- 26-5367
- Acronym
- DIPPER Pilot
- Status last verified
- Oct 2026
- First submitted
- 20 Oct 2026
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adding Acetazolamide on Top of SGLT2 Inhibition in Persons With Type 2 Diabetes ('DIPPER') Pilot Study
- ClinicalTrials.gov ID
- NCT07902726
- Acronym / sponsor ID
- DIPPER Pilot / 26-5367
- Conditions
- T2D
- Keywords
- acetazolamide, SGLT2 inhibition, GFR dip, dose-finding
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 1 Dec 2026 (estimated)
- Primary completion
- 1 Dec 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 29 Oct 2026 (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.
The study aims to determine the acute efficacy and safety of three sequential doses of acetazolamide (62.5 mg, 125 mg, 250 mg) each for 2 weeks in 20 patients with T2D receiving background SGLT2i therapy.
Detailed description
Chronic kidney disease (CKD) is a common complication of type 2 diabetes (T2D) and is associated with an increased risk of kidney failure, cardiovascular disease, and premature death. Although current standard-of-care therapies, including renin-angiotensin-aldosterone system inhibitors (RAASi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and non-steroidal mineralocorticoid receptor antagonists (nsMRA), slow CKD progression, patients continue to experience substantial residual risk of kidney function decline despite treatment. Hyperfiltration remains a central driver of CKD progression and represents an important therapeutic target. Acetazolamide is a carbonic anhydrase inhibitor that has been used clinically for decades and has been shown to reduce glomerular hyperfiltration by increasing distal sodium delivery. Previous studies have demonstrated that acetazolamide produces an acute, reversible reduction in glomerular filtration rate (GFR), although its effects in patients with T2D receiving background SGLT2i therapy have not been evaluated. The Adding AcetazolamIde on top of SGLT2 inhibition in Persons wtih Type 2 Diabetes (DIPPER) pilot study is a phase II, open-label, single-arm, dose-escalation trial evaluating acetazolamide added to background SGLT2i therapy for 16 weeks. The study will evaluate the effect of acetazolamide on glomerular hyperfiltration, as measured by the acute, reversible change in measured GFR following each treatment period. The investigators will also study other important markers such as GFR recovery during washout periods, albuminuria, blood pressure, body weight, body composition, and safety and tolerability. The results of this study will help determine whether adding acetazolamide to SGLT2i therapy safely enhances SGLT2 inhibition's effects on renal hemodynamics, supporting its further evaluation as a potential treatment strategy for patients with T2D.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acetazolamide | Experimental | Drug: Acetazolamide 62.5 mg, Drug: Acetazolamide 125 mg, Drug: Acetazolamide 250 mg, Drug: Dapagliflozin 10mgPatients will be up-titrated starting at acetazolamide 62.5 mg twice daily for 2 weeks, followed by a 2-week washout period. This sequence will be repeated with acetazolamide doses of 125 mg twice daily for 2 weeks and 250 mg twice daily for 2 weeks, with each treatment period followed by a 2-week washout period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Signed and dated written informed consent.
- Adult (≥18 years) at the time of consent
- Established T2D diagnosis as per Diabetes Canada
- HbA1c ≤10.0%
- eGFR ≥45 ml/min/1.73m2
Key exclusion criteria (14 listed)
- Established diagnosis of type 1 diabetes as per Diabetes Canada
- With known or suspected hypersensitivity or allergy to acetazolamide, dapagliflozin or related products
- Iodine intolerance
- Untreated urinary or genital tract infection
- Serum potassium <3.5 mmol/L
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 |
|---|---|---|
| Acetazolamide 62.5 mgOral acetazolamide 62.5 mg twice daily for 2 weeks | Drug | Acetazolamide |
| Acetazolamide 125 mgOral acetazolamide 125 mg twice daily for 2 weeks | Drug | Acetazolamide |
| Acetazolamide 250 mgOral acetazolamide 250 mg twice daily for 2 weeks | Drug | Acetazolamide |
| Dapagliflozin 10mgOral dapagliflozin 10 mg once daily for 16 weeks | Drug | Acetazolamide |
Primary outcome
Iohexol Measured GFR
Time frame: From baseline to the end of treatment at 16 weeks
The primary outcome of this study is the absolute change in measured GFR during each 2-week course of acetazolamide, while on background dapagliflozin therapy. GFR will be measured using plasma clearance of the iohexol contrast agent. The initial "dip" in GFR was selected as the primary outcome as it provides an early and measurable indicator of the treatment effect on kidney physiology. A transient reduction in GFR is a known physiological response to both acetazolamide and SGLT2i, reflecting their effects on hyperfiltration. Assessing this early change allows evaluation of the immediate physiological response to combination therapy but also acts as an indicator of the potential longer-term renal benefits.
10 secondary outcomes
Measured GFR Recovery
Time frame: From baseline to the end of treatment at 16 weeks
eGFR
Time frame: From baseline to the end of treatment at 16 weeks
Urine Albumin-to-Creatinine (UACR)
Time frame: From baseline to the end of treatment at 16 weeks
Systolic Blood Pressure
Time frame: From baseline to the end of treatment at 16 weeks.
Diastolic Blood Pressure
Time frame: From baseline to the end of treatment at 16 weeks
Change in Body Weight
Time frame: From baseline to the end of treatment at 16 weeks
Mean Arterial Pressure
Time frame: From baseline to the end of treatment at 16 weeks
Percent Fat Mass
Time frame: From baseline to the end of treatment at 16 weeks
Percent Extracellular Fluid
Time frame: From baseline to the end of treatment at 16 weeks
Percent Total Body Water
Time frame: From baseline to the end of treatment at 16 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- 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.
Luxcia Kugathasan contact
David Z.I Cherney, MD CM, PhD, FRCPC principal investigator
University Health Network, Toronto General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acetazolamide 62.5 mg, Acetazolamide 125 mg and Acetazolamide 250 mg in people with T2D, run by University Health Network, Toronto at 1 site 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 8 inclusion and 14 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: opening soon, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Cheng Xu (416-340-4800 ext. 8508, cheng.xu@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Iohexol Measured GFR (time frame: From baseline to the end of treatment at 16 weeks). 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 29 Oct 2026.