Type 1 Diabetes MellitusPhase 2/3NCT03899402
Triple Therapy in T1DM
A Phase 2/3 study testing Insulin, Semaglutide and Dapagliflozin in people with Type 1 Diabetes Mellitus, run by State University of New York at Buffalo at 1 site in United States.
Trial summary
To assess whether the addition of dapagliflozin to semaglutide and insulin (triple therapy) improves glycemic control in patients with type 1 diabetes compared with semaglutide and insulin (dual therapy) and insulin only (standard) treatment. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Insulin, Semaglutide and Dapagliflozin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2019to 30 Jun 2026
- Phase
- Phase 2/3
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 Diabetes for at least 1 year on staple use of continuous subcutaneous insulin infusion (CSII) or multiple daily (four or more) injections (MDI) of insulin for last 3 months.
- C-peptide <0.23 nM
- Minimum dose of insulin in Units/kg at entry: 0.5 U/kg for MDI and 0.4 U/kg for CSII
- Regularly measuring blood sugars four or more times daily.
- HbA1c of >7.5%.
- Well versed in CHO counting*
- Age 18-70 years.
- BMI ≥25 kg/m2.
Who cannot join
- Type 1 diabetes for less than 12 months, type 2 diabetes, chronic pancreatitis, MODY
- Previous use of any agent other than insulin for treatment of diabetes in the last 3 months.
- History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalization) within 3 month prior to the screening visit
- Frequent episodes of severe hypoglycemia as defined by more than one episode requiring medical assistance, emergency care (paramedics or emergency room care), and/or glucagon therapy administered by a third-party individual within 1 month prior to the screening visit
- Symptoms of poorly controlled diabetes that would preclude participation in this trial
- Subjects on a commercial weight loss program with ongoing weight loss, or on an intensive exercise program
Show all 32Show fewer
- History of bariatric surgery or lap-band procedure within 12 months prior to screening
- History of Addison's disease or chronic adrenal insufficiency
- History of diabetes insipidus
- Hepatic disease or cirrhosis with Aspartate Aminotransferase (AST) > 3X Upper limit of normal (ULN) and/or Alanine aminotransferase (ALT) > 3X ULN
- Serum Total Bilirubin > 2X ULN unless exclusively caused by Gilbert's Syndrome
- Hemoglobin < 11.0 g/dL (110 g/L) for men; hemoglobin < 10.0 g/dL (100 g/L) for women.
- Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous 3 months or patients with congestive heart failure.
- ESRD on hemodialysis; and or e-GFR < 60 ml/min/1.73m2
- HIV or Hepatitis B/C positive status
- Any other life-threatening, noncardiac disease
- History of pancreatitis
- Women who are pregnant or women of childbearing potential who are not using adequate contraception or who are breast feeding
- Inability to give informed consent
- History of gastroparesis
- History of medullary thyroid carcinoma or MEN 2 syndrome
- History of serious hypersensitivity reaction to these agents
- Painful gallstones
- Alcoholism
- Hypertriglyceridemia (>500 mg/dl)
- Recurrent genital mycotic infection.
- Hypovolemic patients or with chronic renal insufficiency.
- Patients with any malignancy except treated in situ malignancy and basal cell carcinoma of the skin
- Unexplained hematuria
- Patients with a history of diabetic retinopathy
- Use of an investigational agent or therapeutic regimen within 30 days of study
- Participation in any other concurrent interventional clinical trial
Trial locations and contacts
1 site in 1 country.
United States1 site
Diabetes and Endocrinology Research Center of WNY
Williamsville, New York, 14221
About this study
Official title: Triple Therapy for Type 1 Diabetes With Insulin, Semaglutide, and Dapagliflozin
To assess whether the addition of dapagliflozin to semaglutide and insulin (triple therapy) improves glycemic control in patients with type 1 diabetes compared with semaglutide and insulin (dual therapy) and insulin only (standard) treatment.
Read the detailed description
This will be a 52 week study for type 1 diabetics looking into the effect of semaglutide and dapagliflozin on HbA1c and glycemic control.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Insulin, Semaglutide, Dapagliflozin, Placebo to Dapagliflozin
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InsulinDrug
Standard of care insulin for pump or injection and serves as a control
SemaglutideDrug
Also called Ozempic
Injectable weekly GLP-1RA given as open label experimental drug
DapagliflozinDrug
Also called Farxigo
Oral daily SGLT2 Inhibitor given as experimental drug
Placebo to DapagliflozinDrug
Placebo to Dapagliflozin given as a control to the experimental drug
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | Standard of care insulin will be used as an active comparator arm for 1/3 of patients (38 patients) for the entire duration of the study. Receives: Drug: Insulin |
| Dual Therapy | Experimental | Once a week injection of Semaglutide (a GLP-1 receptor agonist) in addition to standard of care insulin for the first six months in 2/3 of patients (76 patients). Semaglutide is a clear, colorless solution that contains 2 mg of semaglutide in a 1.5 mL (1.34 mg/mL) pre-filled, disposable, single-patient-use pen injector. Semaglutide will be started at the 0.25 mg dose for the first two weeks, then increased to 0.5 mg at week 2, and then yet again increased to 1.0 mg at week 4. Receives: Drug: Insulin; Drug: Semaglutide |
| Triple therapy | Experimental | Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of Dapagliflozin (an SGLT-2 inhibitor) added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)). Dapagliflozin will be started at 5 mg for one week, and then increased to 10 mg for the remainder of the study Receives: Drug: Insulin; Drug: Semaglutide; Drug: Dapagliflozin |
| Triple therapy control | Placebo comparator | Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of the Placebo form of Dapagliflozin added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)). Receives: Drug: Insulin; Drug: Semaglutide; Drug: Placebo to Dapagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in HbA1c following dapagliflozin
Change in HbA1c at 6 months following dapagliflozin or placebo therapy in addition to combined semaglutide and insulin treatment.
Measured: 6 months
Secondary outcomes (22)
Change in HbA1c with triple therapy
Change in HbA1c from baseline at 12 months in triple therapy group compared to insulin only group.
Measured: 12 months
Change in HbA1c with semaglutide
Change in HbA1c from baseline at 6 months in dual therapy group (insulin and semaglutide) compared to insulin only group.
Measured: 6 months
Assessment of hyperglycemia level 1
Change in percent Time hyperglycemia Level 1(180-250mg/dl) as assessed by CGM
Measured: 12 months
Assessment of hyperglycemia level 2
Change in percent Time in hyperglycemia Level 2 ( >250mg/dl) as assessed by CGM
Measured: 12 months
Assessment of hypoglycemia
Change in percent Time in hypoglycemia Level 1 (54-70mg/dl) as assessed by CGM
Measured: 12 months
Assessment of percent time glucose in range
Change in percent Time in Range (70- 180 mg/dl) as assessed by CGM
Measured: 12 months
Fructosamine indices
Assessment of fructosamine
Measured: 12 months
Weekly fasting glucose indices
Assessment of change of weekly fasting glucose
Measured: 12 months
Insulin requirement indices
Assessment of the change in insulin requirement
Measured: 12 months
body weight assessment following dapagliflozin
Change in body weight at 6 months between dapagliflozin and placebo groups.
Measured: 6 months
body weight assessment following semaglutide
Change in body weight at 6 months following starting semaglutide compared to standard of care (SOC) group.
Measured: 6 months
body weight assessment following triple therapy
Change in body weight as assessed at 12 months on dapagliflozin and semaglutide compared to SOC therapy.
Measured: 12 months
Systolic Blood pressure assessment after triple therapy
Anti-hypertensive effects including change in systolic BP on dapagliflozin and semaglutide compared to SOC therapy.
Measured: 12 months
Diastolic Blood pressure assessment
Anti-hypertensive effects including change in diastolic BP on dapagliflozin and semaglutide compared to SOC therapy.
Measured: 12 months
Blood pressure medication use
Anti-hypertensive effects including change in numbers of BP medications required in patients dapagliflozin and semaglutide compared to SOC therapy.
Measured: 12 months
Level 2 hypoglycemia assessment
Differences in rates of hypoglycemic events Level 2 (<54mg/dl) between triple therapy and in standard therapy arm.
Measured: 12 months
Severe (level 3) hypoglycemia assessment
Differences in rates of hypoglycemic events Level 3 (<54mg/dl) characterized by altered mental and/or physical status requiring assistance) between triple therapy and in standard therapy arm.
Measured: 12 months
Level 1 hyperglycemia assessment
Differences in rates of Level 1 hyperglycemia (glucose levels >180mg/dl and <250mg dl) between triple therapy and in standard therapy arm.
Measured: 12 months
Level 2 hyperglycemia assessment
Differences in rates of Level 2 hyperglycemia (glucose levels <250mg dl) between triple therapy and in standard therapy arm.
Measured: 12 months
serum ketones assessment
Differences in rates of diabetic ketoacidosis defined as elevated serum ketones (greater than the upper limit of the normal range) in investigative arms.
Measured: 12 months
Urinary ketones assessment
Differences in rates of diabetic ketoacidosis defined as elevated urine ketones (greater than the upper limit of the normal range) in investigative arms.
Measured: 12 months
Diabetic ketoacidosis assessment
Differences in rates of diabetic ketoacidosis defined as Blood pH <7.3 in investigative arms.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2019
- Study start1 May 2019
- Primary completion31 Jan 2026
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by State University of New York at BuffaloThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This will be a two-center, randomized, open-label then double-blind, parallel group, placebo and standard of care controlled prospective study in type 1 diabetes.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- State University of New York at Buffalo
- Sponsor type
- University, hospital or other
- Collaborators
- University of Glasgow, Juvenile Diabetes Research Foundation
- Responsible party
- Principal investigator, paresh Dandona, State University of New York at Buffalo
- Investigators
- Husam Ghanim, PhD, Study director, State University of NY at Buffalo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03899402
- Sponsor's protocol ID
- STUDY00002775
- Other IDs
- 1987
- Status last verified
- May 2026
- First submitted
- 26 Mar 2019
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Timmons JG, Ghanim H, Boyle JG, Greenlaw N, Chaudhuri A, Batra MA, Lindsay RS, Jolly L, Bonner C, McConnachie A, Petrie JR, Dandona P. Insulin, Semaglutide and Dapagliflozin in Adults With Type 1 Diabetes: Design and Methods of Triple Therapy for Type 1 Diabetes (TTT1)-An International Phase 3 Clinical Trial. Diabetes Obes Metab. 2026 Jul 19. doi: 10.1111/dom.71076. Online ahead of print.
PubMed 42473259
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Triple Therapy for Type 1 Diabetes With Insulin, Semaglutide, and Dapagliflozin
- ClinicalTrials.gov ID
- NCT03899402
- Acronym / sponsor ID
- STUDY00002775
- Conditions
- Type 1 Diabetes Mellitus
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 78 participants (actual)
- Lead sponsor
- State University of New York at BuffaloUniversity, hospital or other
- Collaborators
- University of Glasgow, Juvenile Diabetes Research Foundation
- Study start
- 1 May 2019 (actual)
- Primary completion
- 31 Jan 2026 (actual)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 2 Apr 2019 (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.
To assess whether the addition of dapagliflozin to semaglutide and insulin (triple therapy) improves glycemic control in patients with type 1 diabetes compared with semaglutide and insulin (dual therapy) and insulin only (standard) treatment.
Detailed description
This will be a 52 week study for type 1 diabetics looking into the effect of semaglutide and dapagliflozin on HbA1c and glycemic control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- This will be a two-center, randomized, open-label then double-blind, parallel group, placebo and standard of care controlled prospective study in type 1 diabetes.
| Arm | Type | Receives |
|---|---|---|
| Control | Active comparator | Drug: InsulinStandard of care insulin will be used as an active comparator arm for 1/3 of patients (38 patients) for the entire duration of the study. |
| Dual Therapy | Experimental | Drug: Insulin, Drug: SemaglutideOnce a week injection of Semaglutide (a GLP-1 receptor agonist) in addition to standard of care insulin for the first six months in 2/3 of patients (76 patients). Semaglutide is a clear, colorless solution that contains 2 mg of semaglutide in a 1.5 mL (1.34 mg/mL) pre-filled, disposable, single-patient-use pen injector. Semaglutide will be started at the 0.25 mg dose for the first two weeks, then increased to 0.5 mg at week 2, and then yet again increased to 1.0 mg at week 4. |
| Triple therapy | Experimental | Drug: Insulin, Drug: Semaglutide, Drug: DapagliflozinOnce a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of Dapagliflozin (an SGLT-2 inhibitor) added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)). Dapagliflozin will be started at 5 mg for one week, and then increased to 10 mg for the remainder of the study |
| Triple therapy control | Placebo comparator | Drug: Insulin, Drug: Semaglutide, Drug: Placebo to DapagliflozinOnce a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of the Placebo form of Dapagliflozin added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Type 1 Diabetes for at least 1 year on staple use of continuous subcutaneous insulin infusion (CSII) or multiple daily (four or more) injections (MDI) of insulin for last 3 months.
- C-peptide <0.23 nM
- Minimum dose of insulin in Units/kg at entry: 0.5 U/kg for MDI and 0.4 U/kg for CSII
- Regularly measuring blood sugars four or more times daily.
- HbA1c of >7.5%.
Key exclusion criteria (32 listed)
- Type 1 diabetes for less than 12 months, type 2 diabetes, chronic pancreatitis, MODY
- Previous use of any agent other than insulin for treatment of diabetes in the last 3 months.
- History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalization) within 3 month prior to the screening visit
- Frequent episodes of severe hypoglycemia as defined by more than one episode requiring medical assistance, emergency care (paramedics or emergency room care), and/or glucagon therapy administered by a third-party individual within 1 month prior to the screening visit
- Symptoms of poorly controlled diabetes that would preclude participation in this trial
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 |
|---|---|---|
| InsulinStandard of care insulin for pump or injection and serves as a control | Drug | Control, Dual Therapy, Triple therapy, Triple therapy control |
| SemaglutideAlso: OzempicInjectable weekly GLP-1RA given as open label experimental drug | Drug | Dual Therapy, Triple therapy, Triple therapy control |
| DapagliflozinAlso: FarxigoOral daily SGLT2 Inhibitor given as experimental drug | Drug | Triple therapy |
| Placebo to DapagliflozinPlacebo to Dapagliflozin given as a control to the experimental drug | Drug | Triple therapy control |
Primary outcome
Change in HbA1c following dapagliflozin
Time frame: 6 months
Change in HbA1c at 6 months following dapagliflozin or placebo therapy in addition to combined semaglutide and insulin treatment.
22 secondary outcomes
Change in HbA1c with triple therapy
Time frame: 12 months
Change in HbA1c with semaglutide
Time frame: 6 months
Assessment of hyperglycemia level 1
Time frame: 12 months
Assessment of hyperglycemia level 2
Time frame: 12 months
Assessment of hypoglycemia
Time frame: 12 months
Assessment of percent time glucose in range
Time frame: 12 months
Fructosamine indices
Time frame: 12 months
Weekly fasting glucose indices
Time frame: 12 months
Insulin requirement indices
Time frame: 12 months
body weight assessment following dapagliflozin
Time frame: 6 months
body weight assessment following semaglutide
Time frame: 6 months
body weight assessment following triple therapy
Time frame: 12 months
Systolic Blood pressure assessment after triple therapy
Time frame: 12 months
Diastolic Blood pressure assessment
Time frame: 12 months
Blood pressure medication use
Time frame: 12 months
Level 2 hypoglycemia assessment
Time frame: 12 months
Severe (level 3) hypoglycemia assessment
Time frame: 12 months
Level 1 hyperglycemia assessment
Time frame: 12 months
Level 2 hyperglycemia assessment
Time frame: 12 months
serum ketones assessment
Time frame: 12 months
Urinary ketones assessment
Time frame: 12 months
Diabetic ketoacidosis assessment
Time frame: 12 months
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 May 2026.
- Derived from this study: PubMed 42473259Timmons JG, Ghanim H, Boyle JG, Greenlaw N, Chaudhuri A, Batra MA, Lindsay RS, Jolly L, Bonner C, McConnachie A, Petrie JR, Dandona P. Insulin, Semaglutide and Dapagliflozin in Adults With Type 1 Diabetes: Design and Methods of Triple Therapy for Type 1 Diabetes (TTT1)-An International Phase 3 Clinical Trial. Diabetes Obes Metab. 2026 Jul 19. doi: 10.1111/dom.71076. Online ahead of print.
- 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.
Husam Ghanim, PhD study director
State University of NY at Buffalo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Insulin, Semaglutide and Dapagliflozin in people with Type 1 Diabetes Mellitus, run by State University of New York at Buffalo at 1 site in United States.
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 32 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: under way, not looking for participants, as of the sponsor's last update on 29 May 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 United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
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?
Change in HbA1c following dapagliflozin (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03899402, which also lists 1 linked publication.
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 May 2026.