Clincosm LogoSign in Get a demo

ESR-15-11293 - Saxa/Dapa, Safety and Efficacy Study

Sponsor
The University of Texas Health Science Center at San Antonio (Other)
Overall Status
Completed
CT.gov ID
NCT02613897
Collaborator
AstraZeneca (Industry)
56
Enrollment
1
Location
3
Arms
29.9
Duration (Months)
1.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a 16-week, single center, randomized, double-blind, active-controlled, parallel-group, Phase 3b efficacy and safety study of simultaneous administration of saxagliptin 5 mg plus dapagliflozin 10 mg once daily (QD) compared with dapagliflozin plus placebo for saxagliptin, and placebo for saxagliptin plus placebo for dapagliflozin in patients with Type 2 diabetes who have inadequate glycemic control on metformin or metformin/sulfonylurea.

Condition or Disease Intervention/Treatment Phase
N/A

Detailed Description

The study is intended to demonstrate complimentary action of saxagliptin/dapagliflozin added to metformin versus dapagliflozin added to metformin with regard to EGP.

Many medications are approved for the treatment of T2DM; however, the challenge of achieving and maintaining treatment goals within the current sequential therapy approach is linked to shortcomings of older classes of drugs. Metformin is in the biguanide drug class that acts to decrease hepatic glucose output and subsequently, decreases fasting hyperglycemia. Metformin, the oral first-line gold standard agent, is recommended as the initial pharmacological therapy because of its glycemic efficacy, weight neutrality, low risk of hypoglycemia, and beneficial cardiovascular (CV) profile. Current sequential add-on second and third line oral therapy includes oral drugs such as sulfonylureas (SUs) and thiazolidinediones (TZDs). These therapies and insulin are associated with increased risks for weight gain and hypoglycemia; therefore, caution is recommended when using combination therapy with other agents known to cause hypoglycemia. Hypoglycemia is a clinically important issue in optimizing treatment and there is emerging evidence that hypoglycemia is associated with negative CV outcomes. Efforts by patients to lose weight as part of a therapeutic lifestyle program are undermined by therapies that lead to weight gain. The majority of patients with T2DM are overweight or obese, and additional weight gain often results in reduced treatment efficacy.

Over the past few years, it has been widely recognized that the management approach for each T2DM patients' needs to be personalized based on his or her clinical characteristics (e.g., the likelihood of weight gain, risk for hypoglycemia, and lifestyle preferences [e.g., many patients may be reluctant to use injections]) (Inzucchi et al 2012). Based on data from the National Health and Nutrition Examination Survey in 2007 to 2010, HbA1c is not appropriately controlled in approximately one-third of patients using even less stringent targets (Ali et al 2013).

Because of the challenge to achieve glycemic control in patients with T2DM, the progressive nature of the disease, and the limitations of available oral and non-oral therapies, there is a significant medical need for oral combination treatment options and dual add-on therapy in patients with high baseline HbA1c. Expert groups have increasingly suggested making use of combination therapy early after diagnosis to improve glycemic control (Inzucchi et al 2012, Rodbard et al 2009). In a recent study, initiating triple therapy (pathophysiological-based approach) in patients with new onset T2DM versus metformin followed by sequential addition of SUs and basal insulin (treat-to-fail approach) demonstrated a more durable HbA1c reduction over 24 months and less hypoglycemia with initial triple therapy (Abdul-Ghani et al 2014). Initial combination therapy with saxagliptin and dapagliflozin added to metformin may have similar potential for durable glucose lowering in combination with low risk of hypoglycemia.

Treatment with saxagliptin and dapagliflozin, both individually and in combination with metformin, have demonstrated a favorable safety and tolerability profile. These drugs had a low propensity for hypoglycemia, therefore addressing a potential key concern when adding 2 glucose lowering agents simultaneously. These drugs have demonstrated weight neutrality (saxagliptin) or moderate weight reduction (dapagliflozin). Dapagliflozin has also been shown to cause a persistent reduction in HbA1c and weight after 2 years of therapy. Dapagliflozin was recently shown to increase EGP, which, in part, may be mediated by increased plasma glucagon (Merovci et al). In contrast, saxagliptin has been demonstrated to reduce glucagon levels, e.g., in response to a meal (Sjöstrand et al 2014) and vildagliptin, also a DPP-4 inhibitor, has been shown to inhibit EGP (Balas et al 2007).

A second-line oral dual add-on therapy with saxagliptin co-administered with dapagliflozin could be a new option, as part of a triple therapy combination that includes drugs with complementary mechanisms of action, opposing effects on plasma glucagon concentration, and possibly EGP, low risk of hypoglycemia, and the potential for moderate weight loss, providing a more effective and patient-friendly approach to the treatment of T2DM.

Study Design

Study Type:
Interventional
Actual Enrollment :
56 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A 16-wk, Uni-center, Randomized, Double-blind, Parallel, Phase 3b Trial to Evaluate Efficacy of Saxagliptin + Dapagliflozin vs.Dapagliflozin With Regard to EGP in T2DM With Insufficient Glycemic Control on Metformin+/-Sulfonylurea Therapy
Study Start Date :
Jan 1, 2016
Actual Primary Completion Date :
Jun 30, 2018
Actual Study Completion Date :
Jun 30, 2018

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: DAPA/SAXA (dapagliflozin plus saxagliptin)

Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea).

Drug: Saxagliptin
Saxagliptin (Onglyza™) is approved by the US FDA as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. The 5 mg dose will be used for this study as it is the dose that is routinely used in the clinic. In addition, this dose is used in the pivotal studies in the saxagliptin/dapagliflozin clinical program.
Other Names:
  • Onglyza

    • Drug: Dapagliflozin
    Dapagliflozin (Farxiga) is approved by the FDA as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. Dapagliflozin (Farxiga) is also approved in the EU as an adjunct to diet and exercise to improve glycemic control in patients with T2DM for whom metformin use is considered inappropriate due to intolerance, and in combination with other glucose-lowering medicinal products when these, in combination with diet and exercise do not provide adequate glycemic control. The 10 mg dose was chosen for this study because it has been extensively studied in Phase 3 trials and has demonstrated a favorable benefit-risk profile. In addition, this dose is the most commonly used dose in most countries.
    Other Names:
  • Farxiga

    		•
    Active Comparator: DAPA (Dapagliflozin plus placebo)

    Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea).

    Drug: Dapagliflozin
    Dapagliflozin (Farxiga) is approved by the FDA as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. Dapagliflozin (Farxiga) is also approved in the EU as an adjunct to diet and exercise to improve glycemic control in patients with T2DM for whom metformin use is considered inappropriate due to intolerance, and in combination with other glucose-lowering medicinal products when these, in combination with diet and exercise do not provide adequate glycemic control. The 10 mg dose was chosen for this study because it has been extensively studied in Phase 3 trials and has demonstrated a favorable benefit-risk profile. In addition, this dose is the most commonly used dose in most countries.
    Other Names:
  • Farxiga

    		•
    Placebo Comparator: PCB (Placebo plus placebo)

    Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea).

    Drug: Placebo
    Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Change in Endogenous Glucose Production (EGP) [Baseline and 16 weeks]

      All subjects received a Double-Tracer Oral Glucose Tolerance Test (OGTT) with 75g of glucose containing 14C-glucose together with intravenous primed-continuous infusion of 3(3H)-glucose for 240 minutes, at baseline (prior to) and after 16 weeks of therapy. Blood and urine samples were obtained during the OGTT to determine EGP.

    Secondary Outcome Measures

    1. Change in Body Weight [Baseline to 16 weeks]

      Change in body weight from baseline to 16 weeks

    2. Change in BMI [Change from baseline to 16 weeks]

      Change in BMI (body mass index) from study start to 16 weeks

    3. HBA1c [Change from baseline to 16 weeks]

      Change in blood glucose level measured over a 3 month period from study start to 16 weeks

    4. Mean Oral Glucose Tolerance Test (OGTT) [Change from baseline to 16 weeks]

      Measure of change in OGTT from study start to 16 weeks

    5. Change in Lipid Oxidation [Change from baseline to 16 weeks]

      Change in lipid oxidation percentage from baseline to 16 weeks

    6. Change in Glucose Oxidation [Change from baseline to 16 weeks]

      Change in percentage of glucose oxidation from study start to 16 weeks

    7. Change in Fasting Plasma Glucagon (FPG) [Change from baseline to 16 weeks]

      A measure of the change in fasting plasma glucagon from study start to 16 weeks

    8. Change in Free Fatty Acids (FFA) [Change from baseline to 16 weeks]

      Measure of change in Free Fatty Acids from study start to 16 weeks

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Provision of informed consent prior to any study-specific procedures.

    2. Is able to read, understand, and sign the Informed Consent Forms (ICFs) and, if applicable, an Authorization to Use and Disclose Protected Health Information form (consistent with Health Insurance Portability and Accountability Act of 1996 legislation), communicate with the Investigator, and understand and comply with protocol requirements, including the use of diary and glucose meter measurements.

    3. Age = 18-70 years.

    4. Has a diagnosis of T2DM.

    5. Has HbA1c ≥7.5% and ≤11.0% obtained at Screening.

    6. Treated with a stable dose of metformin ≥1000 mg/day or stable dose of metformin (≥ 1000 mg/day) plus sulfonylurea (glipizide, ≥ 5 mg/day; glyburide, ≥ 5 mg/day; glimepiride, ≥ 4 mg/day) for at least 8 weeks prior to Screening.

    7. Has a BMI of 20 to 45 kg/m2 (inclusive) at Screening.

    8. Is male, or is female, and meets all the following criteria:

    • Not pregnant or breastfeeding.

    • Negative pregnancy test result at Visit 1 (Screening).

    • Women of childbearing potential (WOCBP; [including perimenopausal women who have had a menstrual period within 1 year]) must practice and be willing to continue to practice appropriate birth control (defined as a method that results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as implants, injectables, hormonal contraceptives [pills, vaginal rings, or patches], some intrauterine contraceptive devices [levonorgestrel-releasing or copper-T], tubal ligation or occlusion, or a vasectomized partner) during the entire duration of the study. As applicable, all methods must be in effect prior to receiving the first dose of study medication.

    Exclusion Criteria:

    Target Disease Exceptions

    1. Clinically diagnosed with Type I diabetes .

    2. History of diabetic ketoacidosis, hyperosmolar nonketotic coma, or corticosteroid induced Type 2 diabetes.

    Medical History and Concurrent Diseases

    1. History of bariatric surgery or lap-band surgery, or either procedure is planned during the time period of the study.

    2. History of any unstable endocrine, psychiatric, rapidly progressing, or unstable renal disease, or rheumatic disorder, as judged by the Investigator.

    3. Patients who, in the judgment of the Investigator, may be at risk for dehydration or volume depletion that may affect the patient's safety and/or the interpretation of efficacy or safety data.

    4. Has evidence of current abuse of drugs or alcohol or a history of abuse within the past 52 weeks that, in the Investigator's opinion, would cause the individual to be noncompliant.

    Cardiovascular Conditions

    1. Cardiovascular disease within 3 months of Screening (i.e., MI, cardiac surgery, revascularization, unstable angina, stroke, transient ischemic attack, or arrhythmia).

    2. Presence or history of severe congestive heart failure (New York Heart Association Class III and IV [CCNYHA 1994]), unstable or acute congestive heart failure, and/or known left ventricular ejection fraction of ≤40%.

    Note: Eligible patients with congestive heart failure, especially those who are on diuretic therapy, should have careful monitoring of their volume status throughout the study.

    Kidney Conditions

    1. Estimated (eGFR) <60±5 mL/min/1.73 m2 or a measured serum creatinine of >1.4 mg/dL for female patients and >1.5 mg/dL for male patients. If the serum creatinine is ≤ 1.4 (female) or ≤ 1.5 (male) and the eGFR is ≥ 60±5 ml/min/1.73m2, the subject is eligible to participate in the study.

    2. Congenital renal glucosuria. Hepatic Conditions

    3. Significant hepatic disease, including, but not limited to, severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) of >3x upper limit of normal (ULN).

    4. Serum total bilirubin (TB) >2 mg/dL.

    5. History of, or currently have, acute or chronic pancreatitis or have triglyceride concentrations ≥500 mg/dL at Visit 1 (Screening).

    6. Suspicion that the patient is infected with an infectious substance according to World Health Organization risk categories A and B (see Appendix C).

    7. Known severe hepatic disease, including chronic active hepatitis.

    8. Positive serologic evidence of current infectious liver disease, including patients positive for hepatitis B viral antibody IgM, hepatitis B surface antigen, and hepatitis C virus antibody.

    Hematological/Oncological Conditions

    1. Malignancy within 5 years of Visit 1 (Screening), with the exception of treated in situ basal cell or squamous cell carcinoma of the skin.

    2. Hematocrit of <34% for both males and females. Prohibited Medications

    3. Administration of any antihyperglycemic therapy, other than metformin or metformin/sulfonylurea, for more than 14 days (consecutive or not) during the 12 weeks prior to Visit 1 (Screening) and during the study unless per protocol for rescue.

    4. Current treatment with potent cytochrome P450 3A4/5 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin).

    5. Administration of any other investigational drug or participation in any interventional clinical studies 30 days prior to Visit 1 (Screening).

    6. Treatment with systemic corticosteroids for the last 3 months prior to Visit 1 (Screening).

    7. Prescription or over-the-counter weight loss medications within 3 months prior to Visit 1 (Screening).

    Other

    1. Patients with abnormal thyroid stimulating hormone (TSH) or free thyroxine (T4) values at Visit 1 (Screening) will be excluded.

    2. Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the Investigator.

    3. Has clinically significant abnormal laboratory test values (clinical chemistry, hematology, and urinalysis) as judged by the Investigator at Visit 1 (Screening).

    4. Has known contraindications, allergies, or hypersensitivities to any study medication or excipient as outlined in the IBs or local package inserts for saxagliptin and dapagliflozin.

    5. Has a contraindication to metformin use, including known metabolic or lactic acidosis, or any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis.

    6. Is currently pregnant (confirmed with positive pregnancy test) or breast feeding.

    7. Is on a commercial weight loss program with ongoing weight loss more than 5% over the last 3 months prior to Visit 1 (Screening), or is on an intensive exercise program.

    8. Involvement in the planning and/or conduct of the study (applies to both the study sponsor staff and/or staff at the study site).

    9. Patient with any condition that, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient or patient suspected or with confirmed poor protocol or medication compliance.

    10. Previous randomization in the present study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229

    Sponsors and Collaborators

    • The University of Texas Health Science Center at San Antonio
    • AstraZeneca

    Investigators

    • Principal Investigator: Eugenio Cersosimo, MD, The University of Texas Health Science Center at San Antonio
    • Study Director: Ralph A DeFronzo, MD, The University of Texas Health Science Center at San Antonio

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    The University of Texas Health Science Center at San Antonio
    ClinicalTrials.gov Identifier:
    NCT02613897
    Other Study ID Numbers:
    • HSC20150742H
    First Posted:
    Nov 25, 2015
    Last Update Posted:
    Aug 14, 2019
    Last Verified:
    Jun 1, 2019
    Additional relevant MeSH terms:
    Diabetes Mellitus, Type 2
    Dapagliflozin
    Saxagliptin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Arm/Group Description Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea). Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea).
    Period Title: Overall Study
    STARTED 22 22 12
    COMPLETED 22 22 12
    NOT COMPLETED 0 0 0

    Baseline Characteristics

    Arm/Group Title Dapa/Saxa Dapa/Placebo Placebo/Placebo Total
    Arm/Group Description Subjects with type 2 diabetes were enrolled into this study and received the intervention of Dapagliflozin plus Saxa Subjects with type 2 diabetes were enrolled into this study and received the intervention of Dapagliflozin plus placebo Subjects with type 2 diabetes were enrolled into this study and received the intervention of placebo plus placebo Total of all reporting groups
    Overall Participants 22 22 12 56
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    52
    (2)
    52
    (2)
    52
    (2)
    52
    (2)
    Sex: Female, Male (Count of Participants)
    Female
    13
    59.1%
    14
    63.6%
    2
    16.7%
    29
    51.8%
    Male
    9
    40.9%
    8
    36.4%
    10
    83.3%
    27
    48.2%
    Race/Ethnicity, Customized (participants) [Number]
    Hispanic
    18
    81.8%
    18
    81.8%
    9
    75%
    45
    80.4%
    White
    2
    9.1%
    2
    9.1%
    1
    8.3%
    5
    8.9%
    Black
    2
    9.1%
    0
    0%
    2
    16.7%
    4
    7.1%
    Asian
    0
    0%
    2
    9.1%
    0
    0%
    2
    3.6%
    Region of Enrollment (participants) [Number]
    United States
    22
    100%
    22
    100%
    12
    100%
    56
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change in Endogenous Glucose Production (EGP)
    Description All subjects received a Double-Tracer Oral Glucose Tolerance Test (OGTT) with 75g of glucose containing 14C-glucose together with intravenous primed-continuous infusion of 3(3H)-glucose for 240 minutes, at baseline (prior to) and after 16 weeks of therapy. Blood and urine samples were obtained during the OGTT to determine EGP.
    Time Frame Baseline and 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Arm/Group Description Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea). Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo: Placebo
    Measure Participants 22 22 12
    Baseline Measurement
    2.45
    (0.05)
    2.56
    (0.04)
    1.95
    (0.05)
    16 weeks
    2.4
    (0.02)
    2.8
    (0.01)
    2.15
    (0.02)
    2. Secondary Outcome
    Title Change in Body Weight
    Description Change in body weight from baseline to 16 weeks
    Time Frame Baseline to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Arm/Group Description Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea). Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo: Placebo
    Measure Participants 22 22 12
    Mean (Standard Deviation) [Kg]
    -2.28
    (0.67)
    -1.76
    (0.88)
    0.26
    (0.7)
    3. Secondary Outcome
    Title Change in BMI
    Description Change in BMI (body mass index) from study start to 16 weeks
    Time Frame Change from baseline to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Arm/Group Description Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea). Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea).
    Measure Participants 22 22 12
    Mean (Standard Deviation) [Kg/m^2]
    -0.8
    (0.24)
    -0.66
    (0.33)
    0.16
    (0.24)
    4. Secondary Outcome
    Title HBA1c
    Description Change in blood glucose level measured over a 3 month period from study start to 16 weeks
    Time Frame Change from baseline to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Arm/Group Description Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea). Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea).
    Measure Participants 22 22 12
    Mean (Standard Deviation) [percentage change in blood glucose level]
    -1.67
    (0.35)
    -1.46
    (0.22)
    0.44
    (0.36)
    5. Secondary Outcome
    Title Mean Oral Glucose Tolerance Test (OGTT)
    Description Measure of change in OGTT from study start to 16 weeks
    Time Frame Change from baseline to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Arm/Group Description Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea). Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea).
    Measure Participants 22 22 12
    Mean (Standard Deviation) [mg/dl]
    -49.62
    (9.03)
    -44.24
    (7.76)
    20.26
    (9.25)
    6. Secondary Outcome
    Title Change in Lipid Oxidation
    Description Change in lipid oxidation percentage from baseline to 16 weeks
    Time Frame Change from baseline to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Arm/Group Description Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea). Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea).
    Measure Participants 22 22 12
    Mean (Standard Deviation) [percentage of oxidation]
    -11.87
    (2.52)
    22.02
    (2.81)
    -6.69
    (4.95)
    7. Secondary Outcome
    Title Change in Glucose Oxidation
    Description Change in percentage of glucose oxidation from study start to 16 weeks
    Time Frame Change from baseline to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Arm/Group Description Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea). Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea).
    Measure Participants 22 22 12
    Mean (Standard Deviation) [percentage of oxidation]
    -22.07
    (2.22)
    -46.54
    (2.79)
    4.65
    (4.89)
    8. Secondary Outcome
    Title Change in Fasting Plasma Glucagon (FPG)
    Description A measure of the change in fasting plasma glucagon from study start to 16 weeks
    Time Frame Change from baseline to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Arm/Group Description Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea). Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea).
    Measure Participants 22 22 12
    Mean (Standard Deviation) [mg/dl]
    -28.52
    (5.74)
    26.89
    (5.2)
    6.88
    (5.09)
    9. Secondary Outcome
    Title Change in Free Fatty Acids (FFA)
    Description Measure of change in Free Fatty Acids from study start to 16 weeks
    Time Frame Change from baseline to 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Arm/Group Description Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea). Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea).
    Measure Participants 22 22 12
    Mean (Standard Deviation) [mEq/L]
    -0.06
    (0.01)
    -0.01
    (0.02)
    0.00
    (0.7)

    Adverse Events

    Time Frame Adverse events were captured from baseline to 16 weeks
    Adverse Event Reporting Description
    Arm/Group Title DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Arm/Group Description Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea). Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea). Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea).
    All Cause Mortality
    DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/22 (0%) 0/22 (0%) 0/12 (0%)
    Serious Adverse Events
    DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/22 (0%) 0/22 (0%) 0/12 (0%)
    Other (Not Including Serious) Adverse Events
    DAPA/SAXA (Dapagliflozin Plus Saxagliptin) DAPA (Dapagliflozin Plus Placebo) PCB (Placebo Plus Placebo)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/22 (50%) 9/22 (40.9%) 3/12 (25%)
    Gastrointestinal disorders
    Nausea 2/22 (9.1%) 2 1/22 (4.5%) 1 0/12 (0%) 0
    Dry Mouth 2/22 (9.1%) 2 2/22 (9.1%) 2 1/12 (8.3%) 1
    Nervous system disorders
    Light headache 1/22 (4.5%) 1 0/22 (0%) 0 0/12 (0%) 0
    Renal and urinary disorders
    Increased urinary frequency 3/22 (13.6%) 3 3/22 (13.6%) 3 1/12 (8.3%) 1
    Urinary Tract Infection 1/22 (4.5%) 1 1/22 (4.5%) 1 0/12 (0%) 0
    Reproductive system and breast disorders
    Vaginal Itching 2/22 (9.1%) 2 2/22 (9.1%) 2 1/12 (8.3%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Yuejuan Qin
    Organization University of Texas Health San Antonio
    Phone 210-617-5300
    Email qiny@uthscsa.edu
    Responsible Party:
    The University of Texas Health Science Center at San Antonio
    ClinicalTrials.gov Identifier:
    NCT02613897
    Other Study ID Numbers:
    • HSC20150742H
    First Posted:
    Nov 25, 2015
    Last Update Posted:
    Aug 14, 2019
    Last Verified:
    Jun 1, 2019