Trial Outcomes & Findings for A Study to Evaluate the Effect of Dapagliflozin With and Without Saxagliptin on Albuminuria, and to Investigate the Effect of Dapagliflozin and Saxagliptin on HbA1c in Patients With Type 2 Diabetes and CKD (NCT NCT02547935)

NCT ID: NCT02547935

Last Updated: 2019-08-21

Results Overview

HbA1c was analysed at baseline and every 4 weeks during the 24-week treatment period. Only measurements prior to rescue or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a mixed model repeated measures (MMRM) model.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 459 participants
• Primary outcome timeframe: Baseline and Week 24
• Results posted on: 2019-08-21

Participant Flow

Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus with micro- or macro-albuminuria and treated with ACEi or ARB were enrolled into an international, multi-centre study from 21 Sep 2015. The last patient's last visit was 18 May 2018.

Enrolled patients were screened during a 4-week single-blind placebo lead-in period. Patients who met all of the inclusion and none of the exclusion criteria in this period were eligible to be randomised into the 24-week double-blind placebo-controlled treatment period.

Participant milestones

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 milligram (mg) and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Dapagliflozin 10 mg Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.	Placebo Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Overall Study STARTED	155	145	148
Overall Study Received Treatment	152	145	148
Overall Study Full Analysis Set	152	144	148
Overall Study Safety Analysis Set	152	145	148
Overall Study COMPLETED	150	137	143
Overall Study NOT COMPLETED	5	8	5

Reasons for withdrawal

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg Dapagliflozin 10 milligram (mg) and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Dapagliflozin 10 mg Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.	Placebo Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Overall Study Other	0	1	0
Overall Study Withdrawal by Subject	2	3	4
Overall Study Screen Failure	2	0	0
Overall Study Physician Decision	0	1	0
Overall Study Lost to Follow-up	0	2	1
Overall Study Death	1	1	0

Baseline Characteristics

A Study to Evaluate the Effect of Dapagliflozin With and Without Saxagliptin on Albuminuria, and to Investigate the Effect of Dapagliflozin and Saxagliptin on HbA1c in Patients With Type 2 Diabetes and CKD

Baseline characteristics by cohort

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg n=155 Participants Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Dapagliflozin 10 mg n=145 Participants Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.	Placebo n=148 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.	Total n=448 Participants Total of all reporting groups
Age, Continuous	64.0 years STANDARD_DEVIATION 9.21 • n=5 Participants	64.7 years STANDARD_DEVIATION 8.61 • n=7 Participants	64.7 years STANDARD_DEVIATION 8.53 • n=5 Participants	64.4 years STANDARD_DEVIATION 8.78 • n=4 Participants
Age, Customized <65 years	78 Participants n=5 Participants	64 Participants n=7 Participants	68 Participants n=5 Participants	210 Participants n=4 Participants
Age, Customized >=65 years	77 Participants n=5 Participants	81 Participants n=7 Participants	80 Participants n=5 Participants	238 Participants n=4 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	43 Participants n=7 Participants	43 Participants n=5 Participants	131 Participants n=4 Participants
Sex: Female, Male Male	110 Participants n=5 Participants	102 Participants n=7 Participants	105 Participants n=5 Participants	317 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	42 Participants n=5 Participants	32 Participants n=7 Participants	38 Participants n=5 Participants	112 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	113 Participants n=5 Participants	113 Participants n=7 Participants	110 Participants n=5 Participants	336 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	77 Participants n=5 Participants	55 Participants n=7 Participants	64 Participants n=5 Participants	196 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	8 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants	26 Participants n=4 Participants
Race/Ethnicity, Customized Asian	57 Participants n=5 Participants	67 Participants n=7 Participants	53 Participants n=5 Participants	177 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Other	12 Participants n=5 Participants	13 Participants n=7 Participants	18 Participants n=5 Participants	43 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Patients from the Full Analysis Set (all randomised patients who took at least 1 dose of double-blind study drug and had a non missing baseline value and at least one post-baseline efficacy variable value) with non-missing baseline and Week 24 values for HbA1c.

HbA1c was analysed at baseline and every 4 weeks during the 24-week treatment period. Only measurements prior to rescue or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a mixed model repeated measures (MMRM) model.

Outcome measures

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg n=151 Participants Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=145 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.	Placebo Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Adjusted Mean Change From Baseline in Glycosylated Haemoglobin (HbA1c): Comparison of Dapagliflozin 10 mg Plus Saxagliptin 2.5 mg and Placebo at Week 24	-0.85 Percentage of Glycoslyated HbA1c Standard Error 0.09	-0.27 Percentage of Glycoslyated HbA1c Standard Error 0.09	—

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Patients from the Full Analysis Set with non-missing baseline and Week 24 values for UACR.

UACR was analysed at baseline and every 4 weeks during the 24-week treatment period. All measurements regardless of rescue medication or treatment discontinuation were analysed. UACR values were first transformed to logarithms and the results were based on exponentiation of model estimates and expressed as adjusted mean percent change from baseline at Week 24.

Outcome measures

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg n=151 Participants Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=140 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=144 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Adjusted Mean Percent Change From Baseline in Urine Albumin-to-Creatinine Ratio (UACR) at Week 24	-39.1 Percent change Standard Error 5.1	-22.4 Percent change Standard Error 6.6	-1.8 Percent change Standard Error 8.3

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Patients from the Full Analysis Set with non-missing baseline and Week 24 values for total body weight.

Total body weight was measured in kilograms (kg) at baseline and at Week 1 then every 4 weeks during the 24-week treatment period. All measurements regardless of rescue medication or treatment discontinuation were analysed. Total body weight values were first transformed to logarithms and the results were based on exponentiation of model estimates and expressed as adjusted mean percent change from baseline at Week 24.

Outcome measures

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg n=152 Participants Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=144 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=148 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24	-0.65 Percent change Standard Error 0.55	-1.48 Percent change Standard Error 0.56	-0.61 Percent change Standard Error 0.56

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Patients from the Full Analysis Set with non-missing baseline and Week 24 values for FPG.

FPG was analysed at baseline and Week 1 then every 4 weeks during the 24-week treatment period. Only measurements prior to rescue or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a MMRM model.

Outcome measures

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg n=152 Participants Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=144 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=147 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	-17.2 mg/decilitre (dL) Standard Error 5.2	-13.1 mg/decilitre (dL) Standard Error 5.4	-11.2 mg/decilitre (dL) Standard Error 5.5

SECONDARY outcome

Timeframe: From baseline up to Week 24

Population: Patients from the Full Analysis Set with non-missing baseline and at least one post-baseline UACR value.

The percentage of patients meeting the criteria of at least a 30% reduction in UACR, was analysed using a logistic regression model. If no measurement was available at Week 24 the last available post-baseline measurement was carried forward (Last Observation Carried Forward [LOCF]).

Outcome measures

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg n=152 Participants Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=144 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=148 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Percentage of Patients Achieving at Least 30% Reduction in UACR at Week 24	57.0 Percentage of patients	45.0 Percentage of patients	31.3 Percentage of patients

SECONDARY outcome

Timeframe: From baseline to Week 24

Population: Patients from the Full Analysis Set with non-missing baseline and at least one post-baseline HbA1c value.

The percentage of patients meeting the criteria of a less than 7% reduction in HbA1c, was analysed using a logistic regression model. If no measurement was available at Week 24 the last available post-baseline measurement was carried forward (LOCF). Only measurements prior to rescue or treatment discontinuation were analysed.

Outcome measures

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg n=152 Participants Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=144 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=148 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Percentage of Patients Achieving a Reduction in HbA1c of Less Than 7.0% at Week 24	35.1 Percentage of patients	15.0 Percentage of patients	10.3 Percentage of patients

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Patients from the Full Analysis Set with non-missing baseline and Week 24 values for SBP.

Seated SBP was analysed at baseline, Week 1 and every 4 weeks during the 24-week treatment period. All measurements regardless of rescue medication or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a MMRM model.

Outcome measures

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg n=152 Participants Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=144 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=147 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24	-8.8 Millimetre of mercury (mmHg) Standard Error 1.6	-6.9 Millimetre of mercury (mmHg) Standard Error 1.7	-4.1 Millimetre of mercury (mmHg) Standard Error 1.7

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Patients from the Full Analysis Set with non-missing baseline and Week 24 values for HbA1c.

HbA1c was analysed at baseline and every 4 weeks during the 24-week treatment period. Only measurements prior to rescue or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a MMRM model.

Outcome measures

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg n=140 Participants Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Placebo n=145 Participants Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.	Placebo Placebo tablets to match both active products (dapagliflozin and saxagliptin) were taken orally, once daily (in the morning) for 24 weeks.
Adjusted Mean Change From Baseline in HbA1c: Comparison of Dapagliflozin 10 mg and Placebo at Week 24	-0.43 Percentage of Glycoslyated HbA1c Standard Error 0.09	-0.27 Percentage of Glycoslyated HbA1c Standard Error 0.09	—

Adverse Events

Dapagliflozin 10 mg + Saxagliptin 2.5 mg

Serious events: 12 serious events

Other events: 12 other events

Deaths: 1 deaths

Dapagliflozin 10 mg

Serious events: 12 serious events

Other events: 18 other events

Deaths: 1 deaths

Placebo

Serious events: 16 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg n=152 participants at risk Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Dapagliflozin 10 mg n=145 participants at risk Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.	Placebo n=148 participants at risk Placebo tablets to match both active products (dapagliflozin and saxagliptin)were taken orally, once daily (in the morning) for 24 weeks.
Blood and lymphatic system disorders Anaemia	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Blood and lymphatic system disorders Iron deficiency anaemia	0.66% 1/152 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Blood and lymphatic system disorders Splenomegaly	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Cardiac disorders Angina pectoris	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	1.4% 2/148 • Number of events 2 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Cardiac disorders Atrial fibrillation	0.66% 1/152 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Cardiac disorders Cardiac failure	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Cardiac disorders Cardiogenic shock	0.66% 1/152 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Cardiac disorders Myocardial infarction	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	1.4% 2/148 • Number of events 2 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Cardiac disorders Ventricular extrasystoles	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Ear and labyrinth disorders Vertigo	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Gastrointestinal disorders Diarrhoea	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.66% 1/152 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
General disorders Chest pain	0.66% 1/152 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
General disorders Pyrexia	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Hepatobiliary disorders Bile duct stone	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Infections and infestations Diabetic foot infection	0.66% 1/152 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Infections and infestations Emphysematous pyelonephritis	0.66% 1/152 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Infections and infestations Genital infection	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Infections and infestations Groin abscess	0.66% 1/152 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Infections and infestations Pneumonia influenzal	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Infections and infestations Upper respiratory tract infection	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Infections and infestations Urinary tract infection	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	1.4% 2/148 • Number of events 2 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Metabolism and nutrition disorders Hypoglycaemia	1.3% 2/152 • Number of events 2 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Nervous system disorders Cerebrovascular accident	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	1.4% 2/148 • Number of events 3 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Nervous system disorders Dizziness	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Nervous system disorders Headache	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Nervous system disorders Presyncope	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Nervous system disorders Syncope	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	1.4% 2/145 • Number of events 2 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Nervous system disorders Transient ischaemic attack	0.66% 1/152 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Renal and urinary disorders Acute kidney injury	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	1.4% 2/148 • Number of events 2 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Renal and urinary disorders Glomerulonephritis rapidly progressive	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Renal and urinary disorders Urinary retention	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.66% 1/152 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.69% 1/145 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Skin and subcutaneous tissue disorders Diabetic foot	0.66% 1/152 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/148 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Vascular disorders Peripheral ischaemia	0.00% 0/152 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.00% 0/145 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	0.68% 1/148 • Number of events 1 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.

Other adverse events

Measure	Dapagliflozin 10 mg + Saxagliptin 2.5 mg n=152 participants at risk Dapagliflozin 10 mg and saxagliptin 2.5 mg tablets were taken orally, once daily (in the morning) for 24 weeks.	Dapagliflozin 10 mg n=145 participants at risk Dapagliflozin 10 mg tablets were taken orally, once daily (in the morning) for 24 weeks. Patients also took placebo tablets to match saxagliptin.	Placebo n=148 participants at risk Placebo tablets to match both active products (dapagliflozin and saxagliptin)were taken orally, once daily (in the morning) for 24 weeks.
Infections and infestations Influenza	1.3% 2/152 • Number of events 2 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	5.5% 8/145 • Number of events 8 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	1.4% 2/148 • Number of events 2 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.
Infections and infestations Nasopharyngitis	6.6% 10/152 • Number of events 12 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	6.9% 10/145 • Number of events 11 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.	4.1% 6/148 • Number of events 6 • Adverse events (AEs) are reported from Day 1 of the 24-week double-blind treatment period. Non-serious AEs were included up to the last day of double-blind treatment + 4 days. Serious AEs were included up to the last day of double-blind treatment + 30 days, giving a total maximum time frame of 28 weeks. The Safety Analysis Set consisted of all patients who received at least 1 dose of study drug during the 24-week double-blind treatment period.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: +1 302 885 1180

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place