Diabetes Mellitus, Type 2
Conditions
Keywords
Type 2 Diabetes Mellitus
Brief 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.
Interventions
DRUGDapagliflozin
Tablets, Oral, 5mg , Once daily Tablets, Oral, 10mg, Once daily
DRUGSaxagliptin
Tablets, Oral, 2.5mg Once daily Tablets, Oral, 5mg, Once daily
DRUGPlacebo
Matching placebo to dapagliflozin 5mg and 10 mg/saxagliptin 2.5 mg and 5 mg, Tablets, oral, Once daily
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
sponsor
Intervention model description
Eligible subjects with HbA1c of 6.5% to 10.5% at screening will be randomized 1:1:1 to receive dapagliflozin 5 mg, saxagliptin 2.5 mg, or placebo. Blinded HbA1c assessment will be performed at Week 12. All subjects with Week 12 HbA1c \< 7% will remain on previously assigned randomized treatment. Subjects taking dapagliflozin with Week 12 HbA1c ≥ 7% will be re-randomized in a 1:1 ratio to continue on the low-dose treatment (dapagliflozin 5 mg) or up titrate to the high-dose treatment (dapagliflozin 10 mg). Subjects taking saxagliptin with Week 12 HbA1c ≥ 7% will be re-randomized in a 1:1 ratio to continue on the low-dose treatment (saxagliptin 2.5 mg) or up-titrate to the high-dose treatment (saxagliptin 5 mg). Subjects taking placebo with Week 12 HbA1c ≥ 7% will continue on placebo treatment. All placebo subjects and all subjects taking saxagliptin or dapagliflozin with HbA1c \< 7% at Week 12 will go through a dummy 2nd randomization process for maintaining the blinding.
Eligibility
Sex/Gender
ALL
Age
10 Years to 18 Years
Healthy volunteers
No
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26 | Baseline and 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. |
| Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26 | Baseline and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | Baseline and 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. |
| Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | Baseline and 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. |
| Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | Baseline and 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 Versus Placebo: Adjusted Mean Change From Baseline in FPG at Week 26 | Baseline and 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 Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | Baseline and 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. |
| Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | Baseline and 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. |
| Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | Baseline and 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. |
| Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | Baseline and 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. |
| Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | Baseline and 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. |
| Low-dose/High-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | Baseline and 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. |
| Low-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | Baseline and 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. |
| Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26 | Baseline and 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. |
| Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26 | Baseline and 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 Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | Baseline and 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. |
| Saxagliptin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | Baseline and 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. |
| Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | Baseline and 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. |
| Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | Baseline and 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. |
Countries
Argentina, Australia, Brazil, Canada, Chile, Colombia, Finland, India, Israel, Italy, Malaysia, Mexico, New Zealand, Philippines, Poland, Russia, South Korea, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
An initial 26-week short-term (ST) period was followed by a 26-week long-term (LT) safety extension period. The study drug was discontinued at Week 52, after which participants continued in the Non-treatment Follow-up Period until Week 104. Of the 256 participants enrolled, 11 were excluded from analysis due to GCP considerations at the site they originated from (see limitations and caveats for further details).
Participants by arm
| Arm | Count |
|---|---|
| Dapagliflozin Participants were randomised to receive dapagliflozin 5 mg administered orally once daily (low-dose). At Week 14, participants with Week 12 glycated haemoglobin (HbA1c) values \< 7% remained on low-dose dapagliflozin. Participants with Week 12 HbA1c values ≥ 7% were re-randomised in a 1:1 ratio to continue on low-dose treatment or to uptitrate to dapagliflozin 10 mg administered orally once daily (high-dose).
After completion of the ST treatment period, participants could enter the LT treatment period. Participants who were receiving background medication with insulin only or insulin and metformin (not eligible for the third randomisation) continued with their randomised study drug assigned after the second randomisation.
A subset of eligible participants (on background treatment with metformin only and who had HbA1c \< 7.5% at Week 26 or Week 32) were grouped into 2 separate strata for saxagliptin and dapagliflozin, and then randomised 1:1 within each of the strata to either continue or discontinue background medication with metformin at either Week 32 or Week 40. For participants randomised to withdraw background treatment with metformin, those receiving high-dose treatment continued to receive high-dose treatment, whereas those currently receiving low-dose treatment had their doses uptitrated to high-dose treatment. Participants who were randomized to continue background medication with metformin continued with their current dose of dapagliflozin. | 81 |
| Saxagliptin Participants were randomised to receive saxagliptin 2.5 mg administered orally once daily (low-dose). At Week 14, participants with Week 12 HbA1c values \< 7% remained on low-dose saxagliptin. Participants with Week 12 HbA1c values ≥ 7% were re-randomised in a 1:1 ratio to continue on low-dose treatment or to uptitrate to saxagliptin 5 mg administered orally once daily (high-dose).
After completion of the ST treatment period, participants could enter the LT treatment period. Participants who were receiving background medication with insulin only or insulin and metformin (not eligible for the third randomisation) continued with their randomised study drug assigned after the second randomisation.
A subset of eligible participants (on background treatment with metformin only and who had HbA1c \< 7.5% at Week 26 or Week 32) were grouped into 2 separate strata for saxagliptin and dapagliflozin, and then randomised 1:1 within each of the strata to either continue or discontinue background medication with metformin at either Week 32 or Week 40. For participants randomised to withdraw background treatment with metformin, those receiving high-dose treatment continued to receive high-dose treatment, whereas those currently receiving low-dose treatment had their doses uptitrated to high-dose treatment. Participants who were randomized to continue background medication with metformin continued with their current dose of saxagliptin. | 88 |
| Placebo Participants were randomised to receive placebo administered orally once daily. At Week 14, all participants continued on placebo. To maintain blinding, all participants underwent a dummy second randomisation process that was undistinguishable from the actual second randomisation.
After completion of the ST treatment period, participants could enter the LT treatment period. Participants who were receiving background medication with insulin only or insulin and metformin (not eligible for the third randomisation) continued with their randomised study drug assigned after the second randomisation.
At either Week 32 or Week 40 eligible participants receiving placebo (on background treatment with metformin only and who had HbA1c \< 7.5% at Week 26 or Week 32) were randomised 1:1:1 to either withdraw background medication with metformin and switch to active treatment with either saxagliptin 5 mg or dapagliflozin 10 mg or to remain on background medication with metformin and continue with placebo. | 76 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| LT Period | Lost to Follow-up | 0 | 1 | 1 |
| LT Period | Miscellaneous | 0 | 0 | 2 |
| LT Period | Withdrawal by parent/guardian | 0 | 0 | 1 |
| LT Period | Withdrawal by Subject | 1 | 3 | 3 |
| Non-treatment Follow-up Period | Lost to Follow-up | 3 | 4 | 5 |
| Non-treatment Follow-up Period | Miscellaneous | 0 | 1 | 0 |
| Non-treatment Follow-up Period | Withdrawal by parent/guardian | 2 | 3 | 2 |
| Non-treatment Follow-up Period | Withdrawal by Subject | 2 | 1 | 0 |
| ST Period | Lost to Follow-up | 2 | 0 | 1 |
| ST Period | Withdrawal by parent/guardian | 1 | 1 | 1 |
| ST Period | Withdrawal by Subject | 2 | 4 | 6 |
Baseline characteristics
| Characteristic | Dapagliflozin | Saxagliptin | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 14.4 years STANDARD_DEVIATION 2 | 14.5 years STANDARD_DEVIATION 1.75 | 14.7 years STANDARD_DEVIATION 1.64 | 14.5 years STANDARD_DEVIATION 1.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 43 Participants | 34 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 45 Participants | 42 Participants | 123 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Mean Baseline HbA1c | 8.22 Percentage HbA1c STANDARD_DEVIATION 1.459 | 8.02 Percentage HbA1c STANDARD_DEVIATION 1.431 | 7.96 Percentage HbA1c STANDARD_DEVIATION 1.629 | 8.07 Percentage HbA1c STANDARD_DEVIATION 1.502 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 11 Participants | 7 Participants | 12 Participants | 30 Participants |
| Race/Ethnicity, Customized Asian | 18 Participants | 23 Participants | 24 Participants | 65 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 4 Participants | 3 Participants | 14 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 4 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 42 Participants | 50 Participants | 32 Participants | 124 Participants |
| Sex: Female, Male Female | 49 Participants | 53 Participants | 44 Participants | 146 Participants |
| Sex: Female, Male Male | 32 Participants | 35 Participants | 32 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 81 | 0 / 55 | 0 / 21 | 0 / 55 | 0 / 21 | 0 / 7 | 0 / 88 | 0 / 61 | 0 / 26 | 0 / 61 | 0 / 26 | 0 / 13 | 0 / 76 | 0 / 70 | 0 / 70 | 0 / 53 | 0 / 3 | 0 / 3 | 0 / 210 |
| other Total, other adverse events | 35 / 81 | 14 / 55 | 4 / 21 | 26 / 55 | 8 / 21 | 2 / 7 | 37 / 88 | 18 / 61 | 10 / 26 | 23 / 61 | 12 / 26 | 3 / 13 | 39 / 76 | 24 / 70 | 29 / 70 | 2 / 53 | 1 / 3 | 1 / 3 | 0 / 210 |
| serious Total, serious adverse events | 1 / 81 | 0 / 55 | 0 / 21 | 5 / 55 | 1 / 21 | 0 / 7 | 2 / 88 | 1 / 61 | 0 / 26 | 3 / 61 | 1 / 26 | 0 / 13 | 1 / 76 | 1 / 70 | 3 / 70 | 0 / 53 | 0 / 3 | 0 / 3 | 0 / 210 |
Outcome results
Primary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26 | -0.62 Percentage HbA1c | Standard Error 0.218 |
| Placebo | Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26 | 0.41 Percentage HbA1c | Standard Error 0.218 |
p-value: <0.00195% CI: [-1.57, -0.49]ANCOVA
Primary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26 | 0.06 Percentage HbA1c | Standard Error 0.198 |
| Placebo | Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in HbA1c at Week 26 | 0.50 Percentage HbA1c | Standard Error 0.202 |
p-value: 0.07895% CI: [-0.93, 0.05]ANCOVA
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with available data only. Data is pooled for Dapagliflozin 5 mg/10 mg and weighted as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | -0.34 mmol/L | Standard Error 0.365 |
| Placebo | Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | 0.70 mmol/L | Standard Error 0.369 |
p-value: 0.04795% CI: [-2.07, -0.01]ANCOVA
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with available data only. Data is pooled for Dapagliflozin 5 mg/10 mg and weighted as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | -0.42 Percentage HbA1c | Standard Error 0.214 |
| Placebo | Dapagliflozin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | 0.43 Percentage HbA1c | Standard Error 0.207 |
p-value: 0.00495% CI: [-1.44, -0.27]ANCOVA
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with available data only. Data is pooled for Dapagliflozin 5 mg/10 mg and weighted as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | -0.56 mmol/L | Standard Error 0.347 |
| Placebo | Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | 0.56 mmol/L | Standard Error 0.363 |
p-value: 0.02695% CI: [-2.11, -0.13]ANCOVA
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with available data only. Data is pooled for Dapagliflozin 5 mg/10 mg and weighted as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | -0.79 Percentage HbA1c | Standard Error 0.202 |
| Placebo | Dapagliflozin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | 0.40 Percentage HbA1c | Standard Error 0.205 |
p-value: <0.00195% CI: [-1.76, -0.62]ANCOVA
Secondary
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
Population: Uptitration Randomised Participants Data Set: consisted of the subset of randomised participants who were up-titration randomised because their HbA1c is greater than or equal to 7% at Week 12 (regardless of rescue medication initiation). Includes participants with available data only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dapagliflozin | Dapagliflozin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 5.3 Percentage of participants |
| Placebo | Dapagliflozin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 25.0 Percentage of participants |
p-value: 0.18295% CI: [-44.5, 5.7]Fisher Exact
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with available data only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | -0.57 mmol/L | Standard Error 0.374 |
| Placebo | Dapagliflozin Versus Placebo: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | 0.51 mmol/L | Standard Error 0.384 |
p-value: 0.02495% CI: [-2.02, -0.14]ANCOVA
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with Baseline HbA1c \>= 7% and available data only. Data is pooled for Dapagliflozin 5 mg/10 mg and Saxagliptin 2.5 mg/5 mg and weighted as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dapagliflozin | Low-dose/High-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 27.3 Percentage of participants |
| Placebo | Low-dose/High-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 24.4 Percentage of participants |
| Placebo | Low-dose/High-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 10.0 Percentage of participants |
p-value: 0.04295% CI: [1, 11.4]Weighted Logistic Regression
p-value: 0.17595% CI: [0.7, 7.4]Weighted Logistic Regression
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with Baseline HbA1c \>= 7% and available data only. Data is pooled for Dapagliflozin 5 mg/10 mg and Saxagliptin 2.5 mg/5 mg and weighted as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dapagliflozin | Low-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 35.6 Percentage of participants |
| Placebo | Low-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 28.9 Percentage of participants |
| Placebo | Low-dose Versus Placebo (Weighted): Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 10.0 Percentage of participants |
p-value: 0.00995% CI: [1.4, 13.2]Weighted Logistic Regression
p-value: 0.04295% CI: [1.1, 13.5]Weighted Logistic Regression
Secondary
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
Population: Uptitration Randomised Participants Data Set: consisted of the subset of randomised participants who were up-titration randomised because their HbA1c is greater than or equal to 7% at Week 12 (regardless of rescue medication initiation). Includes participants with available data only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26 | -1.62 mmol/L | Standard Error 0.689 |
| Placebo | Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26 | -0.98 mmol/L | Standard Error 0.683 |
| Placebo | Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26 | -2.38 mmol/L | Standard Error 0.734 |
| Saxagliptin 2.5 mg | Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in FPG at Week 26 | -0.56 mmol/L | Standard Error 0.763 |
p-value: 0.47695% CI: [-2.39, 1.12]ANCOVA
p-value: 0.07595% CI: [-3.81, 0.18]ANCOVA
Secondary
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
Population: Uptitration Randomised Participants Data Set: consisted of the subset of randomised participants who were up-titration randomised because their HbA1c is greater than or equal to 7% at Week 12 (regardless of rescue medication initiation). Includes participants with available data only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26 | -0.74 Percentage HbA1c | Standard Error 0.368 |
| Placebo | Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26 | -0.71 Percentage HbA1c | Standard Error 0.384 |
| Placebo | Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26 | -0.16 Percentage HbA1c | Standard Error 0.361 |
| Saxagliptin 2.5 mg | Low-dose Versus Uptitration to the High Dose: Adjusted Mean Change From Baseline in HbA1c at Week 26 | 0.07 Percentage HbA1c | Standard Error 0.372 |
p-value: 0.95595% CI: [-1, 0.94]ANCOVA
p-value: 0.6495% CI: [-1.2, 0.74]ANCOVA
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with Baseline HbA1c \>= 7% and available data only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dapagliflozin | Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 26.6 Percentage of participants |
| Placebo | Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 21.3 Percentage of participants |
| Placebo | Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 10.0 Percentage of participants |
p-value: 0.01995% CI: [1.2, 11.7]Regression, Logistic
p-value: 0.11495% CI: [0.8, 8.6]Regression, Logistic
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with available data only. Data is pooled for Saxagliptin 2.5 mg/5 mg and weighted as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | 0.18 mmol/L | Standard Error 0.331 |
| Placebo | Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | 0.73 mmol/L | Standard Error 0.359 |
p-value: 0.26895% CI: [-1.5, 0.42]ANCOVA
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with available data only. Data is pooled for Saxagliptin 2.5 mg/5 mg and weighted as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | -0.04 Percentage HbA1c | Standard Error 0.19 |
| Placebo | Saxagliptin Low-dose/High-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | 0.47 Percentage HbA1c | Standard Error 0.2 |
p-value: 0.06795% CI: [-1.05, 0.04]ANCOVA
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with available data only. Data is pooled for Saxagliptin 2.5 mg/5 mg and weighted as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | 0.63 mmol/L | Standard Error 0.424 |
| Placebo | Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in FPG at Week 26 | 0.34 mmol/L | Standard Error 0.446 |
p-value: 0.64495% CI: [-0.92, 1.5]ANCOVA
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with available data only. Data is pooled for Saxagliptin 2.5 mg/5 mg and weighted as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | 0.07 Percentage HbA1c | Standard Error 0.188 |
| Placebo | Saxagliptin Low-dose Versus Placebo (Weighted): Adjusted Mean Change From Baseline in HbA1c at Week 26 | 0.47 Percentage HbA1c | Standard Error 0.194 |
p-value: 0.14695% CI: [-0.92, 0.14]ANCOVA
Secondary
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
Population: Uptitration Randomised Participants Data Set: consisted of the subset of randomised participants who were up-titration randomised because their HbA1c is greater than or equal to 7% at Week 12 (regardless of rescue medication initiation). Includes participants with available data only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dapagliflozin | Saxagliptin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 8.7 Percentage of participants |
| Placebo | Saxagliptin Low-dose Versus Uptitration to the High Dose: Percentage of Participants With Baseline HbA1c ≥ 7% Who Achieved HbA1c < 7% at Week 26 | 15.0 Percentage of participants |
p-value: 0.6595% CI: [-29.8, 16.5]Fisher Exact
Secondary
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
Population: Randomised Participants Data Set: consisted of all randomised participants who receive at least one dose of study medication during the treatment period. Includes participants with available data only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in FPG at Week 26 | 0.08 mmol/L | Standard Error 0.413 |
| Placebo | Saxagliptin Versus Placebo: Adjusted Mean Change From Baseline in FPG at Week 26 | 0.19 mmol/L | Standard Error 0.428 |
p-value: 0.83395% CI: [-1.15, 0.92]ANCOVA