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CompletedNCT03199053Updated Jun 21, 2024Results posted

Study to Evaluate Safety and Efficacy of Dapagliflozin and Saxagliptin in Patients With Type 2 Diabetes Mellitus (T2DM) Aged 10 to Below 18 Years Old

A Phase 3 interventional study of Dapagliflozin and Saxagliptin in Diabetes Mellitus, Type 2, sponsored by AstraZeneca. Completed at 122 sites in 23 countries. Open to participants aged 10 Years to 18 Years. Per ClinicalTrials.gov, last updated 2024-06-21.

Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
256
Allocation
Randomized
Ages
10 Years to 18 Years
Sex
All
01

Study summary

The primary objective of this study is to determine if there will be a greater mean reduction from baseline in glycated hemoglobin (HbA1c) achieved after 26 weeks of oral double-blind add-on therapy of dapagliflozin or saxagliptin compared to placebo in paediatric T2DM patients with HbA1c levels of 6.5 to 10.5% on diet and exercise and metformin, insulin, or metformin plus insulin.

02

Conditions studied

  • Diabetes Mellitus, Type 2

Keywords

  • Type 2 Diabetes Mellitus
03

In context

Diabetes Mellitus, Type 2

9,589 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,332 are open to participants now.

This study's enrollment of 256 is above the median of 81 across 7,713 interventional studies indexed under Diabetes Mellitus, Type 2.

Browse Diabetes Mellitus, Type 2 studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,492 studies on the registry; 266 are open to participants now.

Of its 368 completed or terminated interventional studies of FDA-regulated products, 176 (48%) have results posted.

Browse AstraZeneca studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
10 Years to 18 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Signed Written Informed Consent
  • Target Population
  • Previously diagnosed with Type 2 Diabetes Mellitus by World Health Organization/ADA criteria
  • HbA1c between 6.5% and 10.5% obtained at screening.
  • Currently on diet and exercise and stable dose of at least 1000 mg metformin (IR or XR) for a minimum of 8 weeks, or stable dose of insulin for a minimum of 8 weeks, or a stable combination of at least 1000 mg metformin (IR or XR) and insulin for a minimum of 8 weeks prior to randomization. For those children on insulin, investigators will confirm that attempts at removing insulin from the subject's therapeutic regimen had been previously made but had not been successful.
  • Age and Reproductive Status
  • Male and female patients eligible if 10 years of age, up to but not including 18 years of age at the time of enrollment/screening. At least 30% of total subjects will be between the ages of 10 and 14 years and at least one third, but no more than two thirds, female subjects.
  • Women of childbearing potential must have a negative pregnancy test within 24 hours prior to the start of study drug.
  • Women must not be breastfeeding.
  • Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs: saxagliptin, and dapagliflozin, plus 5 half-lives of study drugs or 30 days (whichever is longer), plus 30 days (duration of ovulatory cycle) for a total of 60 days post treatment completion.

Exclusion criteria

Exclusion Criteria:

  • Target Disease Exceptions
  • Presence of Type 1 diabetes, as demonstrated by Preexisting diagnosis of Type 1 diabetes,
  • Previous diagnosis of monogenic etiology of Type 2 diabetes
  • Diabetes ketoacidosis (DKA) within 6 months of screening
  • Current use of the following medications for the treatment of diabetes, or use within the specified timeframe prior to screening for the main study:
  • Eight weeks: sulfonylureas, alpha glucosidase inhibitors, metiglinide, oral or injectable incretins or incretin mimetics, other antidiabetes medications not otherwise specified.
  • Sixteen weeks: thiazolidinediones, DPP-4 inhibitors (with no reported medication related AEs related to DPP-4 inhibitors), sodium glucose cotransporter-2 (SGLT-2) inhibitors (with no reported medication related AEs related to SGLT-2 inhibitors)
  • Initiation or discontinuation of prescription or non-prescription weight loss drugs within 8 weeks of screening. Use of prescription or non-prescription weight loss drugs must be stable during the study.
  • Medical History and Concurrent Diseases
  • Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical trials, or breastfeeding
  • History of unstable or rapidly progressive renal disease
  • History of unresolved vesico-ureteral reflux
  • History of or current, acute or chronic pancreatitis
  • History of hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis
  • Malignancy within 5 years of the screening visit (with the exception of treated basal cell or treated squamous cell carcinoma)
  • Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for > 4 weeks within 3 months prior to the Day 1 visit
  • Physical and Laboratory Test Findings
  • Abnormal renal function,
  • An abnormal thyroid-stimulating hormone (TSH) value at enrollment will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded.
  • Hematuria (confirmed by microscopy at screening) with no explanation as judged by the Investigator up to randomization.
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2× upper limit of normal (ULN), or clinically significant hepatic disease.
  • Serum total bilirubin (TB) > 2x ULN unless exclusively caused by Gilbert's syndrome
  • Positive serologic evidence of current infectious liver disease including anti hepatitis A virus (HAV) (IgM), hepatitis B surface antigen (HBsAg), or anti hepatitis C virus (HCV). Patients who have isolated positive anti-hepatitis B surface antibodies may be included.
  • Anemia of any etiology
  • Volume-depleted subjects.
  • Allergies and Adverse Drug Reaction
  • Known allergy, sensitivity or contraindication to any study drug or its excipient/vehicle
  • Other Exclusion Criteria
  • Subject is currently abusing alcohol or other drugs or has done so within the last 6 months prior to the screening visit.
  • Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and Sponsor/designee approval is required.)
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
  • Psychiatric or cognitive disorder that will, in the opinion of investigators, limit the subject's ability to comply with the study medications and monitoring.
  • Subjects who have contraindications to therapy as outlined in the saxagliptin and dapagliflozin Investigator Brochure or local package inserts.
  • Participation and receiving IP in another clinical study during the prior 3 months
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
256 participants (actual)

Study arms

  • Experimental
    Low dose Dapagliflozin

    Oral route. Start with a low dose of dapagliflozin administered once daily and remain on the low dose regardless of your HbA1c at week 12.

    Drug: Dapagliflozin

  • Experimental
    Low dose/high dose Dapagliflozin

    Oral route. Start with a low dose of Dapagliflozin administered once daily and up titrate to the high dose Dapagliflozin administered once daily if HbA1c \>= 7% at week 12

    Drug: Dapagliflozin

  • Experimental
    Low dose Saxagliptin

    Oral route. Start with a low dose of saxagliptin administered once daily and remain on the low dose regardless of your HbA1c at week 12

    Drug: Saxagliptin

  • Experimental
    Low dose/high dose Saxagliptin

    Oral route. Start with a low dose of saxagliptin administered once daily and up titrate to the high dose if HbA1c \>= 7% at week 12

    Drug: Saxagliptin

  • Placebo comparator
    Placebo arm

    Oral route. Placebo tablets administered for 52 weeks

    Drug: Placebo

Interventions

  • DrugDapagliflozin

    Tablets, Oral, 5mg , Once daily Tablets, Oral, 10mg, Once daily

    Also known as: Forxiga

  • DrugSaxagliptin

    Tablets, Oral, 2.5mg Once daily Tablets, Oral, 5mg, Once daily

    Also known as: Onglyza

  • DrugPlacebo

    Matching placebo to dapagliflozin 5mg and 10 mg/saxagliptin 2.5 mg and 5 mg, Tablets, oral, Once daily

06

What researchers measure

Primary outcomes

  1. Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on multiple imputation washout (MI-WO) within each arm using the data from placebo participants with Week 26 data.

    Time frame: Baseline and Week 26

  2. Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

    Time frame: Baseline and Week 26

Secondary outcomes

  1. Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Dapagliflozin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

    Time frame: Baseline and Week 26

  2. Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Saxagliptin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

    Time frame: Baseline and Week 26

  3. Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Dapagliflozin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

    Time frame: Baseline and Week 26

  4. Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Saxagliptin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

    Time frame: Baseline and Week 26

  5. Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

    Time frame: Baseline and Week 26

  6. Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in FPG at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

    Time frame: Baseline and Week 26

  7. Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Dapagliflozin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

    Time frame: Baseline and Week 26

  8. Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Saxagliptin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

    Time frame: Baseline and Week 26

  9. Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Dapagliflozin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

    Time frame: Baseline and Week 26

  10. Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Saxagliptin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

    Time frame: Baseline and Week 26

  11. Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26

    A logistic regression model adjusting for sex, age group, background antidiabetes medication and Baseline HbA1c was used. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

    Time frame: Baseline and Week 26

  12. Low-dose/High-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26

    A weighted logistic regression model adjusting for sex, age group, background antidiabetes medication and Baseline HbA1c was used. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

    Time frame: Baseline and Week 26

  13. Low-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26

    A weighted logistic regression model adjusting for sex, age group, background antidiabetes medication and Baseline HbA1c was used. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

    Time frame: Baseline and Week 26

  14. Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

    Time frame: Baseline and Week 26

  15. Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26

    Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

    Time frame: Baseline and Week 26

  16. Dapagliflozin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26

    A Fisher's exact test was used and unadjusted difference in percentage of participants and Clopper-Pearson CIs presented using imputed data. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

    Time frame: Baseline and Week 26

  17. Saxagliptin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26

    A Fisher's exact test was used and unadjusted difference in percentage of participants and Clopper-Pearson CIs presented using imputed data. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

    Time frame: Baseline and Week 26

07

Results

Posted Apr 17, 2024
Limitations and caveats
Due to legal dispute, the source documents could not be accessed for 11 participants at 1 site. All data from this site were excluded as documented in the statistical analysis plan.

Participant flow

A total of 245 patients were randomised from 94 sites in 21 countries. Participants were initially randomised in a 1:1:1 ratio to receive dapagliflozin 5 mg, saxagliptin 2.5 mg, or placebo.

ST Period
Participant flow — ST Period
MilestoneDapagliflozinSaxagliptinPlacebo
Started818876
Week 14 no uptitration randomisation39360
Week 14 uptitration randomisation42520
Completed768368
Not completed558
Withdrew: Withdrawal by subject246
Withdrew: Withdrawal by parent/guardian111
Withdrew: Lost to follow-up201
LT Period
Participant flow — LT Period
MilestoneDapagliflozinSaxagliptinPlacebo
Started768368
Randomised withdrawal patients data set13258
Excluded from randomised withdrawal patients data set686368
Randomised to continue metformin6122
Randomised metformin withdrawal7136
Completed757961
Not completed147
Withdrew: Withdrawal by subject133
Withdrew: Withdrawal by parent/guardian001
Withdrew: Lost to follow-up011
Withdrew: Miscellaneous002
Non-treatment Follow-up Period
Participant flow — Non-treatment Follow-up Period
MilestoneDapagliflozinSaxagliptinPlacebo
Started747759
Completed676852
Not completed797
Withdrew: Withdrawal by subject210
Withdrew: Withdrawal by parent/guardian232
Withdrew: Lost to follow-up345
Withdrew: Miscellaneous010

Outcome measures

PrimaryDapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on multiple imputation washout (MI-WO) within each arm using the data from placebo participants with Week 26 data.

Time frame:
Baseline and Week 26
Reported as:
Mean · Percentage HbA1c
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26
Percentage HbA1cDapagliflozinPlacebo
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26-0.62 ± 0.2180.41 ± 0.218
Statistical analysis
  • Dapagliflozin vs Placebo · ANCOVA · p = < 0.001 · Adjusted mean difference: -1.03 · 95% CI -1.57 to -0.49
PrimarySaxagliptin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

Time frame:
Baseline and Week 26
Reported as:
Mean · Percentage HbA1c
Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26
Percentage HbA1cSaxagliptinPlacebo
Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 260.06 ± 0.1980.50 ± 0.202
Statistical analysis
  • Saxagliptin vs Placebo · ANCOVA · p = 0.078 · Adjusted mean difference: -0.44 · 95% CI -0.93 to 0.05
SecondaryDapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Dapagliflozin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

Time frame:
Baseline and Week 26
Reported as:
Mean · Percentage HbA1c
Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Percentage HbA1cDapagliflozin 5 mg/10 mg (Weighted)Placebo (Weight = 1)
Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26-0.42 ± 0.2140.43 ± 0.207
Statistical analysis
  • Dapagliflozin 5 mg/10 mg (Weighted) vs Placebo (Weight = 1) · ANCOVA · p = 0.004 · Adjusted mean difference: -0.86 · 95% CI -1.44 to -0.27
SecondarySaxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Saxagliptin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

Time frame:
Baseline and Week 26
Reported as:
Mean · Percentage HbA1c
Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Percentage HbA1cSaxagliptin 2.5 mg/5 mg (Weighted)Placebo (Weight = 1)
Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26-0.04 ± 0.1900.47 ± 0.200
Statistical analysis
  • Saxagliptin 2.5 mg/5 mg (Weighted) vs Placebo (Weight = 1) · ANCOVA · p = 0.067 · Adjusted mean difference: -0.51 · 95% CI -1.05 to 0.04
SecondaryDapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Dapagliflozin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

Time frame:
Baseline and Week 26
Reported as:
Mean · Percentage HbA1c
Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Percentage HbA1cDapagliflozin 5 mg/10 mg (Weighted)Placebo (Weight = 1)
Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26-0.79 ± 0.2020.40 ± 0.205
Statistical analysis
  • Dapagliflozin 5 mg/10 mg (Weighted) vs Placebo (Weight = 1) · ANCOVA · p = < 0.001 · Adjusted mean difference: -1.19 · 95% CI -1.76 to -0.62
SecondarySaxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Saxagliptin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

Time frame:
Baseline and Week 26
Reported as:
Mean · Percentage HbA1c
Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26
Percentage HbA1cSaxagliptin 2.5 mg/5 mg (Weighted)Placebo (Weight = 1)
Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 260.07 ± 0.1880.47 ± 0.194
Statistical analysis
  • Saxagliptin 2.5 mg/5 mg (Weighted) vs Placebo (Weight = 1) · ANCOVA · p = 0.146 · Adjusted mean difference: -0.39 · 95% CI -0.92 to 0.14
SecondaryDapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

Time frame:
Baseline and Week 26
Reported as:
Mean · mmol/L
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
mmol/LDapagliflozinPlacebo
Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26-0.57 ± 0.3740.51 ± 0.384
Statistical analysis
  • Dapagliflozin vs Placebo · ANCOVA · p = 0.024 · Adjusted mean difference: -1.08 · 95% CI -2.02 to -0.14
SecondarySaxagliptin Versus Placebo: Adjusted Mean Change From Baseline in FPG at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

Time frame:
Baseline and Week 26
Reported as:
Mean · mmol/L
Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in FPG at Week 26
mmol/LSaxagliptinPlacebo
Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in FPG at Week 260.08 ± 0.4130.19 ± 0.428
Statistical analysis
  • Saxagliptin vs Placebo · ANCOVA · p = 0.833 · Adjusted mean difference: -0.11 · 95% CI -1.15 to 0.92
SecondaryDapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Dapagliflozin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

Time frame:
Baseline and Week 26
Reported as:
Mean · mmol/L
Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
mmol/LDapagliflozin 5 mg/10 mg (Weighted)Placebo (Weight = 1)
Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26-0.34 ± 0.3650.70 ± 0.369
Statistical analysis
  • Dapagliflozin 5 mg/10 mg (Weighted) vs Placebo (Weight = 1) · ANCOVA · p = 0.047 · Adjusted mean difference: -1.04 · 95% CI -2.07 to -0.01
SecondarySaxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Saxagliptin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

Time frame:
Baseline and Week 26
Reported as:
Mean · mmol/L
Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
mmol/LSaxagliptin 2.5 mg/5 mg (Weighted)Placebo (Weight = 1)
Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 260.18 ± 0.3310.73 ± 0.359
Statistical analysis
  • Saxagliptin 2.5 mg/5 mg (Weighted) vs Placebo (Weight = 1) · ANCOVA · p = 0.268 · Adjusted mean difference: -0.54 · 95% CI -1.50 to 0.42
SecondaryDapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Dapagliflozin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

Time frame:
Baseline and Week 26
Reported as:
Mean · mmol/L
Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
mmol/LDapagliflozin 5 mg/10 mg (Weighted)Placebo (Weight = 1)
Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26-0.56 ± 0.3470.56 ± 0.363
Statistical analysis
  • Dapagliflozin 5 mg/10 mg (Weighted) vs Placebo (Weight = 1) · ANCOVA · p = 0.026 · Adjusted mean difference: -1.12 · 95% CI -2.11 to -0.13
SecondarySaxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Saxagliptin participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

Time frame:
Baseline and Week 26
Reported as:
Mean · mmol/L
Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26
mmol/LSaxagliptin 2.5 mg/5 mg (Weighted)Placebo (Weight = 1)
Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 260.63 ± 0.4240.34 ± 0.446
Statistical analysis
  • Saxagliptin 2.5 mg/5 mg (Weighted) vs Placebo (Weight = 1) · ANCOVA · p = 0.644 · Adjusted mean difference: 0.29 · 95% CI -0.92 to 1.50
SecondaryPercentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26

A logistic regression model adjusting for sex, age group, background antidiabetes medication and Baseline HbA1c was used. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

Time frame:
Baseline and Week 26
Reported as:
Number · Percentage of participants
Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
Percentage of participantsDapagliflozinSaxagliptinPlacebo
Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 2626.621.310.0
Statistical analysis
  • Dapagliflozin vs Placebo · Regression, Logistic · p = 0.019 · Adjusted odds ratio: 3.8 · 95% CI 1.2 to 11.7
  • Saxagliptin vs Placebo · Regression, Logistic · p = 0.114 · Adjusted odds ratio: 2.6 · 95% CI 0.8 to 8.6
SecondaryLow-dose/High-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26

A weighted logistic regression model adjusting for sex, age group, background antidiabetes medication and Baseline HbA1c was used. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 0; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 2; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

Time frame:
Baseline and Week 26
Reported as:
Number · Percentage of participants
Low-dose/High-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
Percentage of participantsDapagliflozin 5 mg/10 mg (Weighted)Saxagliptin 2.5 mg/5 mg (Weighted)Placebo (Weight = 1)
Low-dose/High-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 2627.324.410.0
Statistical analysis
  • Dapagliflozin 5 mg/10 mg (Weighted) vs Placebo (Weight = 1) · Weighted Logistic Regression · p = 0.042 · Adjusted odds ratio: 3.5 · 95% CI 1.0 to 11.4
  • Saxagliptin 2.5 mg/5 mg (Weighted) vs Placebo (Weight = 1) · Weighted Logistic Regression · p = 0.175 · Adjusted odds ratio: 2.3 · 95% CI 0.7 to 7.4
SecondaryLow-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26

A weighted logistic regression model adjusting for sex, age group, background antidiabetes medication and Baseline HbA1c was used. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data. Participants were weighted as follows: participants who had HbA1c \< 7% at Week 12 and remained on low-dose were assigned a weight of 1; participants who had HbA1c \>= 7% at Week 12 and continued on the low-dose were assigned a weight of 2; participants who had HbA1c \>= 7% at Week 12 and received the high-dose were assigned a weight of 0; all participants who do not undergo second randomisation were assigned a weight of 1. Placebo participants were assigned a weight of 1.

Time frame:
Baseline and Week 26
Reported as:
Number · Percentage of participants
Low-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
Percentage of participantsDapagliflozin 5 mg/10 mg (Weighted)Saxagliptin 2.5 mg/5 mg (Weighted)Placebo (Weight = 1)
Low-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 2635.628.910.0
Statistical analysis
  • Dapagliflozin 5 mg/10 mg (Weighted) vs Placebo (Weight = 1) · Weighted Logistic Regression · p = 0.009 · Adjusted odds ratio: 4.4 · 95% CI 1.4 to 13.2
  • Saxagliptin 2.5 mg/5 mg (Weighted) vs Placebo (Weight = 1) · Weighted Logistic Regression · p = 0.042 · Adjusted odds ratio: 3.8 · 95% CI 1.1 to 13.5
SecondaryLow-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline HbA1c as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

Time frame:
Baseline and Week 26
Reported as:
Mean · Percentage HbA1c
Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26
Percentage HbA1cDapagliflozin 10 mgDapagliflozin 5 mgSaxagliptin 5 mgSaxagliptin 2.5 mg
Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26-0.74 ± 0.368-0.71 ± 0.384-0.16 ± 0.3610.07 ± 0.372
Statistical analysis
  • Dapagliflozin 10 mg vs Dapagliflozin 5 mg · ANCOVA · p = 0.955 · Adjusted mean difference: -0.03 · 95% CI -1.00 to 0.94
  • Saxagliptin 5 mg vs Saxagliptin 2.5 mg · ANCOVA · p = 0.640 · Adjusted mean difference: -0.23 · 95% CI -1.20 to 0.74
SecondaryLow-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26

Data was analysed with an ANCOVA model with treatment, sex, age group and background antidiabetes medication as factors and Baseline FPG as covariate. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

Time frame:
Baseline and Week 26
Reported as:
Mean · mmol/L
Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26
mmol/LDapagliflozin 10 mgDapagliflozin 5 mgSaxagliptin 5 mgSaxagliptin 2.5 mg
Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26-1.62 ± 0.689-0.98 ± 0.683-2.38 ± 0.734-0.56 ± 0.763
Statistical analysis
  • Dapagliflozin 10 mg vs Dapagliflozin 5 mg · ANCOVA · p = 0.476 · Adjusted mean difference: -0.64 · 95% CI -2.39 to 1.12
  • Saxagliptin 5 mg vs Saxagliptin 2.5 mg · ANCOVA · p = 0.075 · Adjusted mean difference: -1.81 · 95% CI -3.81 to 0.18
SecondaryDapagliflozin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26

A Fisher's exact test was used and unadjusted difference in percentage of participants and Clopper-Pearson CIs presented using imputed data. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

Time frame:
Baseline and Week 26
Reported as:
Number · Percentage of participants
Dapagliflozin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
Percentage of participantsDapagliflozin 10 mgDapagliflozin 5 mg
Dapagliflozin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 265.325.0
Statistical analysis
  • Dapagliflozin 10 mg vs Dapagliflozin 5 mg · Fisher Exact · p = 0.182 · Unadjusted difference in percentage: -19.7 · 95% CI -44.5 to 5.7
SecondarySaxagliptin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26

A Fisher's exact test was used and unadjusted difference in percentage of participants and Clopper-Pearson CIs presented using imputed data. Missing Week 26 data was handled based on MI-WO within each arm using the data from placebo participants with Week 26 data.

Time frame:
Baseline and Week 26
Reported as:
Number · Percentage of participants
Saxagliptin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26
Percentage of participantsSaxagliptin 5 mgSaxagliptin 2.5 mg
Saxagliptin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 268.715.0
Statistical analysis
  • Saxagliptin 5 mg vs Saxagliptin 2.5 mg · Fisher Exact · p = 0.650 · Unadjusted difference in percentage: -6.3 · 95% CI -29.8 to 16.5

Adverse events

Collected over All-cause mortality: Up to Week 104 Serious and other AEs: Up to 52 Weeks + 30 days (Week 56). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Weeks 1 to 14: Dapagliflozin 5 mg0/81 (0%)1/81 (1.2%)35/81 (43.2%)
Weeks 14 to 26: Dapagliflozin 5 mg0/55 (0%)0/55 (0%)14/55 (25.5%)
Weeks 14 to 26: Dapagliflozin 10 mg0/21 (0%)0/21 (0%)4/21 (19%)
Weeks 26 to 56: Dapagliflozin 5 mg0/55 (0%)5/55 (9.1%)26/55 (47.3%)
Weeks 26 to 56: Dapagliflozin 10 mg0/21 (0%)1/21 (4.8%)8/21 (38.1%)
Weeks 32 or 40 to 56: Dapagliflozin 10 mg + Metformin Withdrawal0/7 (0%)0/7 (0%)2/7 (28.6%)
Weeks 1 to 14: Saxagliptin 2.5 mg0/88 (0%)2/88 (2.3%)37/88 (42%)
Weeks 14 to 26: Saxagliptin 2.5 mg0/61 (0%)1/61 (1.6%)18/61 (29.5%)
Weeks 14 to 26: Saxagliptin 5 mg0/26 (0%)0/26 (0%)10/26 (38.5%)
Weeks 26 to 56: Saxagliptin 2.5 mg0/61 (0%)3/61 (4.9%)23/61 (37.7%)
Weeks 26 to 56: Saxagliptin 5 mg0/26 (0%)1/26 (3.8%)12/26 (46.2%)
Weeks 32 or 40 to 56: Saxagliptin 5 mg + Metformin Withdrawal0/13 (0%)0/13 (0%)3/13 (23.1%)
Weeks 1 to 14: Placebo0/76 (0%)1/76 (1.3%)39/76 (51.3%)
Weeks 14 to 26: Placebo0/70 (0%)1/70 (1.4%)24/70 (34.3%)
Weeks 26 to 32 or 40: Placebo0/70 (0%)3/70 (4.3%)29/70 (41.4%)
Weeks 32 or 40 to 56: Placebo0/53 (0%)0/53 (0%)2/53 (3.8%)
Weeks 32 or 40 to 56: Placebo to Dapagliflozin 10 mg + Metformin Withdrawal0/3 (0%)0/3 (0%)1/3 (33.3%)
Weeks 32 or 40 to 56: Placebo to Saxagliptin 5 mg + Metformin Withdrawal0/3 (0%)0/3 (0%)1/3 (33.3%)
Week 56 to 104: Non-treatment Follow-up Period0/210 (0%)0/210 (0%)0/210 (0%)
Most frequent serious events
Showing 10 of 18
Most frequent serious events
EventWeeks 1 to 14: Dapagliflozin 5 mgWeeks 14 to 26: Dapagliflozin 5 mgWeeks 14 to 26: Dapagliflozin 10 mgWeeks 26 to 56: Dapagliflozin 5 mgWeeks 26 to 56: Dapagliflozin 10 mgWeeks 32 or 40 to 56: Dapagliflozin 10 mg + Metformin WithdrawalWeeks 1 to 14: Saxagliptin 2.5 mgWeeks 14 to 26: Saxagliptin 2.5 mgWeeks 14 to 26: Saxagliptin 5 mgWeeks 26 to 56: Saxagliptin 2.5 mgWeeks 26 to 56: Saxagliptin 5 mgWeeks 32 or 40 to 56: Saxagliptin 5 mg + Metformin WithdrawalWeeks 1 to 14: PlaceboWeeks 14 to 26: PlaceboWeeks 26 to 32 or 40: PlaceboWeeks 32 or 40 to 56: PlaceboWeeks 32 or 40 to 56: Placebo to Dapagliflozin 10 mg + Metformin WithdrawalWeeks 32 or 40 to 56: Placebo to Saxagliptin 5 mg + Metformin WithdrawalWeek 56 to 104: Non-treatment Follow-up Period
HaematuriaRenal and urinary disorders0/810/550/210/551/210/70/880/610/260/610/260/130/760/700/700/530/30/30/210
GastritisGastrointestinal disorders0/810/550/210/550/210/70/880/610/260/611/260/130/760/700/700/530/30/30/210
HyperglycaemiaMetabolism and nutrition disorders0/810/550/210/550/210/70/880/610/262/610/260/131/760/701/700/530/30/30/210
Splenic ruptureInjury, poisoning and procedural complications0/810/550/211/550/210/70/880/610/260/610/260/130/760/700/700/530/30/30/210
Glycosylated haemoglobin increasedInvestigations0/810/550/211/550/210/70/880/610/260/610/260/130/760/700/700/530/30/30/210
Euglycaemic diabetic ketoacidosisMetabolism and nutrition disorders0/810/550/211/550/210/70/880/610/260/610/260/130/760/700/700/530/30/30/210
LymphadenitisBlood and lymphatic system disorders0/810/550/211/550/210/70/880/610/260/610/260/130/760/700/700/530/30/30/210
GastroenteritisInfections and infestations0/810/550/211/550/210/70/880/610/260/610/260/130/760/700/700/530/30/30/210
Urinary tract infectionInfections and infestations0/810/550/211/550/210/70/880/610/260/610/260/130/760/700/700/530/30/30/210
Accidental overdoseInjury, poisoning and procedural complications0/810/550/211/550/210/70/880/610/260/610/260/130/760/700/700/530/30/30/210
Most frequent other events
Showing 10 of 206
Most frequent other events
EventWeeks 1 to 14: Dapagliflozin 5 mgWeeks 14 to 26: Dapagliflozin 5 mgWeeks 14 to 26: Dapagliflozin 10 mgWeeks 26 to 56: Dapagliflozin 5 mgWeeks 26 to 56: Dapagliflozin 10 mgWeeks 32 or 40 to 56: Dapagliflozin 10 mg + Metformin WithdrawalWeeks 1 to 14: Saxagliptin 2.5 mgWeeks 14 to 26: Saxagliptin 2.5 mgWeeks 14 to 26: Saxagliptin 5 mgWeeks 26 to 56: Saxagliptin 2.5 mgWeeks 26 to 56: Saxagliptin 5 mgWeeks 32 or 40 to 56: Saxagliptin 5 mg + Metformin WithdrawalWeeks 1 to 14: PlaceboWeeks 14 to 26: PlaceboWeeks 26 to 32 or 40: PlaceboWeeks 32 or 40 to 56: PlaceboWeeks 32 or 40 to 56: Placebo to Dapagliflozin 10 mg + Metformin WithdrawalWeeks 32 or 40 to 56: Placebo to Saxagliptin 5 mg + Metformin WithdrawalWeek 56 to 104: Non-treatment Follow-up Period
Vitamin d deficiencyMetabolism and nutrition disorders2/811/550/212/550/210/74/881/610/260/611/260/135/761/702/700/530/31/30/210
Ligament sprainInjury, poisoning and procedural complications0/810/550/210/550/210/71/880/611/260/610/260/130/761/700/700/531/30/30/210
NasopharyngitisInfections and infestations1/812/550/211/551/210/72/881/610/260/610/262/132/760/703/701/530/30/30/210
PharyngotonsillitisInfections and infestations1/810/550/211/551/211/70/880/610/260/610/260/131/760/701/700/530/30/30/210
TonsillitisInfections and infestations0/810/550/210/550/211/71/880/610/260/610/260/130/760/700/700/530/30/30/210
HeadacheNervous system disorders6/815/550/212/552/210/72/881/610/261/610/260/131/762/701/700/530/30/30/210
DysmenorrhoeaReproductive system and breast disorders0/811/550/210/552/210/71/881/610/260/610/260/132/760/701/700/530/30/30/210
AsthmaRespiratory, thoracic and mediastinal disorders0/810/550/210/550/210/70/880/610/260/610/261/130/760/701/700/530/30/30/210
EpistaxisRespiratory, thoracic and mediastinal disorders1/810/550/210/550/210/70/880/610/260/610/261/131/760/700/700/530/30/30/210
ToothacheGastrointestinal disorders0/810/550/211/551/210/70/880/612/261/611/260/130/760/700/700/530/30/30/210

Baseline characteristics

Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period.

Age, Continuous
Age, Continuous(years)DapagliflozinSaxagliptinPlaceboTotal
Mean14.4 ± 2.0014.5 ± 1.7514.7 ± 1.6414.5 ± 1.80
Sex: Female, Male
Sex: Female, Male(Participants)DapagliflozinSaxagliptinPlaceboTotal
Female495344146
Male32353299
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)DapagliflozinSaxagliptinPlaceboTotal
Hispanic or Latino454334122
Not Hispanic or Latino364542123
Unknown or Not Reported0000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)DapagliflozinSaxagliptinPlaceboTotal
White425032124
Black or African American74314
Asian18232465
Native Hawaiian or Other Pacific Islander0033
American Indian or Alaska Native1171230
Other3429
Mean Baseline HbA1c
Mean Baseline HbA1c(Percentage HbA1c)DapagliflozinSaxagliptinPlaceboTotal
Mean8.22 ± 1.4598.02 ± 1.4317.96 ± 1.6298.07 ± 1.502
08

Study locations

122 sites
  • Research Site
    Sacramento, California 95821, United States
  • Research Site
    New Haven, Connecticut 06519, United States
  • Research Site
    Hialeah, Florida 33012, United States
  • Research Site
    Hialeah, Florida 33016, United States
  • Research Site
    Hollywood, Florida 33021, United States
  • Research Site
    Miami, Florida 33144, United States
  • Research Site
    Miami, Florida 33155, United States
  • Research Site
    Miami, Florida 33165, United States
  • Research Site
    Miami Springs, Florida 33166, United States
  • Research Site
    Atlanta, Georgia 30322, United States
  • Research Site
    Atlanta, Georgia 30341, United States
  • Research Site
    Idaho Falls, Idaho 83404, United States
  • Research Site
    Neptune City, New Jersey 07753, United States
  • Research Site
    Memphis, Tennessee 38116, United States
  • Research Site
    Memphis, Tennessee 38119, United States
  • Research Site
    Edinburg, Texas 78539, United States
  • Research Site
    Harlingen, Texas 78550, United States
  • Research Site
    McAllen, Texas 78503, United States
  • Research Site
    San Antonio, Texas 78229, United States
  • Research Site
    Charlottesville, Virginia 22903, United States
  • Research Site
    Buenos Aires, 6500, Argentina
  • Research Site
    Buenos Aires, C1180AAX, Argentina
  • Research Site
    CABA, C1119ACN, Argentina
  • Research Site
    Ciudad de Buenos Aires, C1405BCH, Argentina
  • Research Site
    San Miguel de Tucumán, 4000, Argentina
  • Research Site
    San Miguel de Tucumán, T4000IHE, Argentina
  • Research Site
    Blacktown, 2148, Australia
  • Research Site
    Brasília, 71625-009, Brazil
  • Research Site
    Curitiba, 80810-040, Brazil
  • Research Site
    Fortaleza, 60170-320, Brazil
  • Research Site
    Fortaleza, 60430-270, Brazil
  • Research Site
    Passo Fundo, 99010-080, Brazil
  • Research Site
    Porto Alegre, 90430-001, Brazil
  • Research Site
    Porto Alegre, 91350-250, Brazil
  • Research Site
    Ribeirão Preto, 14051-104, Brazil
  • Research Site
    Santa Maria, 97015-530, Brazil
  • Research Site
    São Paulo, 01223-001, Brazil
  • Research Site
    São Paulo, 05652-900, Brazil
  • Research Site
    Montreal, Quebec H1T 2M4, Canada
  • Research Site
    Santiago, 7500710, Chile
  • Research Site
    Armenia, 630004, Colombia
  • Research Site
    Barranquilla, 80020, Colombia
  • Research Site
    Tampere, 33520, Finland
  • Research Site
    Ahmedabad, 380008, India
  • Research Site
    Aurangabad, 431003, India
  • Research Site
    Bangalore, 560002, India
  • Research Site
    Bikaner, 334003, India
  • Research Site
    Chandigarh, 160012, India
  • Research Site
    Coimbatore, 641009, India
  • Research Site
    Hyderabad, 500012, India
  • Research Site
    Kolkata, 700054, India
  • Research Site
    Kozhikode, 67300, India
  • Research Site
    Nashik, 422002, India
  • Research Site
    Pune, 411030, India
  • Research Site
    Visakhapatnam, 531011, India
  • Research Site
    Haifa, 3109601, Israel
  • Research Site
    Ancona, 60123, Italy
  • Research Site
    Naples, 80138, Italy
  • Research Site
    Roma, 00165, Italy
  • Research Site
    George Town, 10450, Malaysia
  • Research Site
    Ipoh, 30990, Malaysia
  • Research Site
    Johor Bahru, 80100, Malaysia
  • Research Site
    Klang, 41200, Malaysia
  • Research Site
    Kota Kinabalu, 88996, Malaysia
  • Research Site
    Kuala Lumpur, 50586, Malaysia
  • Research Site
    Kuching, 93586, Malaysia
  • Research Site
    Malacca, 75400, Malaysia
  • Research Site
    Putrajaya, 62250, Malaysia
  • Research Site
    Seremban, 70300, Malaysia
  • Research Site
    Seri Manjung, 32040, Malaysia
  • Research Site
    Taiping, 34000, Malaysia
  • Research Site
    Boca del Rio, 94290, Mexico
  • Research Site
    Celaya, 38000, Mexico
  • Research Site
    Ciudad Madero, 89440, Mexico
  • Research Site
    Cuernavaca, 62209, Mexico
  • Research Site
    Cuernavaca, 62290, Mexico
  • Research Site
    Culiacán, 80230, Mexico
  • Research Site
    Durango, 34000, Mexico
  • Research Site
    Guadalajara, 44150, Mexico
  • Research Site
    Juriquilla, 76230, Mexico
  • Research Site
    Mérida, 97000, Mexico
  • Research Site
    México, 06700, Mexico
  • Research Site
    México, D.F., 11410, Mexico
  • Research Site
    Monterrey, 64460, Mexico
  • Research Site
    Monterrey, 64620, Mexico
  • Research Site
    San Juan del Río, 76800, Mexico
  • Research Site
    Veracruz, 91900, Mexico
  • Research Site
    Zapopan, 45116, Mexico
  • Research Site
    Grafton, 1023, New Zealand
  • Research Site
    Tauranga, 3110, New Zealand
  • Research Site
    Wellington, 6021, New Zealand
  • Research Site
    Quezon City, 1100, Philippines
  • Research Site
    Quezon City, 1112, Philippines
  • Research Site
    San Fernando City, 2000, Philippines
  • Research Site
    Warsaw, 01-868, Poland
  • Research Site
    Izhevsk, 426009, Russia
  • Research Site
    Moscow, 125993, Russia
  • Research Site
    Ufa, 450000, Russia
  • Research Site
    Daejeon, 35233, South Korea
  • Research Site
    Incheon, 22332, South Korea

Showing the first 100 of 122 sites across 23 countries.

09

References and documents

Publications

  • Shehadeh N, Barrett T, Galassetti P, Karlsson C, Monyak J, Iqbal N, Tamborlane WV. Dapagliflozin or Saxagliptin in Pediatric Type 2 Diabetes. NEJM Evid. 2023 Dec;2(12):EVIDoa2300210. doi: 10.1056/EVIDoa2300210. Epub 2023 Oct 4. PubMed 38320500 ↗

Study documents

  • Study protocol · Feb 7, 2022
  • Statistical analysis plan · Dec 7, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting information: Study protocol, Statistical analysis plan

Time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Access criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Data sharing details ↗ · astrazenecagroup-dt.pharmacm.com

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Oct 2017 to primary completion in Feb 2023, 63 months.

Results were first posted in Apr 2024, 1 year 2 months after primary completion.

Of 430 industry-sponsored phase 3 interventional studies under Diabetes Mellitus, Type 2, half reached primary completion within 19 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 26. This study's 63 months is above that.

Counting every sponsor, half of 510 studies reached it within 20 months; a quarter within 14 and three quarters within 30.

How these figures are worked out, and which studies are left out of them.

Registered
Jun 22, 2017
First posted
Jun 26, 2017
StartActual
Oct 11, 2017
Primary completionActual
Feb 1, 2023
CompletionActual
Jan 3, 2024
Results first posted
Apr 17, 2024
Last update
Jun 21, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jun 21, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03199053
Lead sponsor
AstraZeneca
Responsible party
Sponsor
First posted
Jun 26, 2017
Start date
Oct 11, 2017
Primary completion
Feb 1, 2023
Completion
Jan 3, 2024
Results posted
Apr 17, 2024
Last update
Jun 21, 2024

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in May 2024. You cannot join it, but the record below documents what was studied.

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Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Dapagliflozin · Saxagliptin

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Diabetes Mellitus, Type 2 →

Other studies from this sponsor

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