Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Women with a history of gestational diabetes (GDM) are at substantially increased risk of type 2 diabetes mellitus (T2DM). Compared with the general population, these women are more likely to be overweight or obese. Moreover, weight gain after GDM is significantly associated with T2DM, independent of baseline body weight. Weight gain, particularly increased central adiposity after delivery, is strongly associated with deterioration of β-cell compensation for insulin resistance. Taken together, our findings and other studies support increased abdominal fat as the strongest factor associated with declining B-cell compensation for insulin resistance in prior GDM women at high risk for T2DM. Dapagliflozin is a novel highly selective SGLT2 inhibitor that improves glycemic control by reducing renal glucose reabsorption leading to urinary glucose excretion. Its efficacy and safety has been studied in multiple randomized controlled trials including an add-on to metformin compared with a placebo. To the extent that glucotoxicity contributes to the demise in β-cell function in subjects with impaired glucose, SGLT2 inhibitors also may prove useful in the treatment of "prediabetes." An additional secondary benefit of SGLT2 inhibition is the elimination of calories in the form of glucose. The loss of glucose with attendant caloric loss contributes to weight loss; in addition, improvements in β cell function have been seen. Weight loss seen with SGLT2 inhibitors is similar to that seen with glucagon-like peptide 1 analogs, and may be more acceptable because they are oral agents. A consistent finding in all dapagliflozin studies has been a reduction in blood pressure. The investigators hypothesize that combination dapagliflozin -metformin treatment over a 24-week period will have a greater positive impact on body weight, anthropometric measurements and glycemic and cardiometabolic parameters than dapagliflozin or metformin monotherapy in overweight/obese at-risk women with a history of GDM.
Following written consent, all study patients will undergo the following clinical, metabolic and laboratory evaluations before and during treatment. To ensure that patients remain unidentified, all study subjects will be assigned an individual study identifier which includes the study acronym, patient initials, and unique number. All blood samples will be obtained and results identified and reported using this unique study identifier. A full physical examination will be performed and vital signs (blood pressure, respiration and temperature) determined. Trained personnel using standardized protocols at the baseline and follow-up examination will obtain anthropometric measurements and blood specimens. Absolute body weight, height, waist and hip circumference, body fat distribution (waist/hip {WHR}) and waist/height ratio ({WHtR}) and blood pressure (BP) will be determined. Body weight will be measured to the nearest 0.1 kg using a calibrated digital scale with participants in light clothing and no shoes. Height will be measured to the nearest centimeter. The total body adiposity (total fatness), defined as the accumulation of body fat without regard to regional distribution, will be expressed as BMI and calculated as weight (kg)/ height (m) 2. The circumference measurements will be taken in the upright position using a 15-mm width flexible metric tape held close to the body but not tight enough to indent the skin. Waist circumference (WC) will be measured at the narrowest level midway between the lowest ribs and the iliac crest and hip circumference measured at the widest level over the buttocks while the subjects are standing and breathing normally. The WHR and WHtR will be calculated for measure of body fat distribution.
All patients will randomly be assigned to one of 3 medication treatment groups-- dapagliflozin-metformin (DAP-MET; 5 mg DAP/ MET 1000 mg BID), metformin XR (MET 1000 mg BID) or dapagliflozin (DAP 10 mg QD); all subjects will be allocated to one of these 3 groups based on computer-generated random numbers using a block randomization method. Oral glucose tolerance tests (OGTTs) with glucose (G) and insulin (I) measured at 0, 30, 60, and 120 after glucose load to assess diabetes, fasting (FBG) and mean blood glucose (MBG) concentrations, insulin resistance and pancreatic ß-cell function will be performed prior to randomization and at 20-24 weeks after full doses of study medications are reached. Mean blood glucose (MBG) concentrations will be calculated by summing glucose values obtained at 0,30,60 and 120 minutes during the OGTT and dividing by 4. At the initial lab evaluation, creatinine and calculated eGFR, TSH, and ß-hCG will be determined for study inclusion. Baseline blood samples will also be analyzed for lipid profiles and liver enzymes.
All patients will receive the same counseling concerning the benefits of lifestyle modification through diet and exercise. The patients will be also encouraged to increase daily exercise (such as walking, using stairs), although this will not be formally assessed. The participants will receive further encouragement to adhere to the regime during follow-up phone calls. Side effects of the treatment and reason for any withdrawals from the study will be recorded.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DAPA/MET Extended Release (XR) | Experimental | Dapagliflozin plus metformin XR- 5 mg/1000 mg with meal for 4 weeks DAPA/MET XR- 5mg/1000 mg BID final dose for 20 weeks |
|
| Dapaglifloxin | Active Comparator | Dapagliflozin- 10 mg once daily before first meal for 24 weeks |
|
| Metformin XR | Active Comparator | Metformin XR with 500 mg once a day for 2 weeks, followed by 500 mg twice a day for 2 weeks, followed by 500 mg in the morning (AM), 1000 mg in the evening ( PM) for 2 weeks, with 1000 mg twice a day as the final dose for 20 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DAPA/MET XR | Drug | final dose- 5 mg dapagliflozin/1000 mg glucophage XR BID for 20-24 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Body Weight | Change in absolute body weight with combination therapy compared to monotherapy from baseline to week 24 | Change from baseline (time 0) to study end (24 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Percent Body Weight | Change in percent body weight with combination therapy compared to monotherapy from baseline to week 24 | Change from baseline (time 0) to study end (24 weeks) |
| Body Mass Index (BMI) |
Not provided
Inclusion Criteria:
• Overweight/obese (BMI >25) females 18 years to 45 years of age, who experienced gestational diabetes (GDM) during recent (within 12 months) pregnancy
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Karen E Elkind-Hirsch, PhD | Woman's Hospital, Louisiana | Principal Investigator |
| Renee Harris, MD | Woman's Hospital, Louisiana | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Woman's Hospital | Baton Rouge | Louisiana | 70815 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33345876 | Derived | Elkind-Hirsch KE, Seidemann E, Harris R. A randomized trial of dapagliflozin and metformin, alone and combined, in overweight women after gestational diabetes mellitus. Am J Obstet Gynecol MFM. 2020 Aug;2(3):100139. doi: 10.1016/j.ajogmf.2020.100139. Epub 2020 May 16. |
Not provided
Not provided
Will publish findings. Individual patient information will be revealed only to patient
Not provided
Not provided
Not provided
Not provided
3 patients not randomized since reluctant to take medication
Patients recruited from Woman's Hospital post delivery
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | DAPA/MET XR | Dapagliflozin plus metformin XR- 5 mg/1000 mg with meal for 4 weeks DAPA/MET XR- 5mg/1000 mg BID final dose for 20 weeks DAPA/MET XR: final dose- 5 mg dapagliflozin/1000 mg glucophage XR BID for 20-24 weeks |
| FG001 | Dapaglifloxin | Dapagliflozin- 10 mg once daily before first meal for 24 weeks DAPA: 10 mg dapagliflozin QD for 20-24 weeks |
| FG002 | Metformin XR | Metformin XR with 500 mg once a day for 2 weeks, followed by 500 mg twice a day for 2 weeks, followed by 500 mg in the AM, 1000 mg in the PM for 2 weeks, with 1000 mg twice a day as the final dose for 20 weeks MET XR: 1000 mg Metformin XR BID for 20-24 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
within 1 year postpartum of GDM pregnancy
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | DAPA/MET XR | Dapagliflozin plus metformin XR- 5 mg/1000 mg with meal for 4 weeks DAPA/MET XR- 5mg/1000 mg BID final dose for 20 weeks DAPA/MET XR: final dose- 5 mg dapagliflozin/1000 mg glucophage XR BID for 20-24 weeks |
| BG001 | Dapaglifloxin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Body Weight | Change in absolute body weight with combination therapy compared to monotherapy from baseline to week 24 | Posted | Mean | Standard Deviation | kilograms | Change from baseline (time 0) to study end (24 weeks) |
|
6 months while participating in trial
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DAPA/MET XR | Dapagliflozin plus metformin XR- 5 mg/1000 mg with meal for 4 weeks DAPA/MET XR- 5mg/1000 mg BID final dose for 20 weeks DAPA/MET XR: final dose- 5 mg dapagliflozin/1000 mg glucophage XR BID for 20-24 weeks |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Yeast infection | Renal and urinary disorders | Non-systematic Assessment |
Important limitations were the small number completed patients per drug group and only 24 weeks of therapy. Surrogate measures were for central adiposity; use of dual-energy x-ray absorptiometry to measure body composition would increase accuracy
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Karen Elkind-Hirsch, Director of Research | Woman's Hospital | 225 231-5278 | karen.elkind-hirsch@womans.org |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Aug 31, 2018 | Mar 12, 2019 | ICF_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 10, 2018 | Mar 14, 2019 | Prot_SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D011236 | Prediabetic State |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C529054 | dapagliflozin |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| DAPA | Drug | 10 mg dapagliflozin QD for 20-24 weeks |
|
|
| MET XR | Drug | 1000 mg Metformin XR BID for 20-24 weeks |
|
|
BMI (measure of overall adiposity) in combination therapy compared to monotherapy after 24 weeks of treatment
| 24 weeks of treatment |
| Waist Circumference (WC) | Waist size (measure of truncal adiposity)with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment |
| Waist- to -Hip Ratio (WHR; Measure of Central Adiposity) | Waist-to-hip ratio with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment |
| Waist-to-height Ratio (WHtR) | Waist divided by height a( measure of central adiposity) with combination therapy compared to monotherapy after 24 weeks of therapy | 24 weeks of treatment |
| Diastolic Blood Pressure (DBP) | Diastolic blood pressure with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment) |
| Systolic Blood Pressure (SBP) | Systolic blood pressure with combination therapy compared to monotherapy after 24 weeks of therapy | 24 weeks of treatment |
| Liver Enzymes | ALT/AST ratio with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment |
| Total Cholesterol Levels (CHOL) | Cholesterol levels with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment |
| Triglyceride (TRG) Levels | Triglyceride levels with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment |
| Fasting Blood Glucose (FBG) | Fasting blood glucose levels with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment |
| Mean Blood Glucose (MBG) During an OGTT | Mean blood glucose after glucose load with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment |
| Fasting Insulin Sensitivity (HOMA-IR) | HOMA index of insulin resistance calculated from fasting insulin and glucose with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment |
| Matsuda Sensitivity Index (SI OGTT) | Surrogate measure of insulin sensitivity derived from OGTT with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment |
| First Phase Insulin Secretion (IGI/HOMA-IR) | Corrected early insulin response to glucose challenge [(insulinogenic index (IGI)/ divided by fasting insulin resistance index (HOMA-IR)] with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment |
| Noncompliant with visits |
|
| moved out of state |
|
| intolerant of side effects |
|
Dapagliflozin- 10 mg once daily before first meal for 24 weeks DAPA: 10 mg dapagliflozin QD for 20-24 weeks |
| BG002 | Metformin XR | Metformin XR with 500 mg once a day for 2 weeks, followed by 500 mg twice a day for 2 weeks, followed by 500 mg in the AM, 1000 mg in the PM for 2 weeks, with 1000 mg twice a day as the final dose for 20 weeks MET XR: 1000 mg Metformin XR BID for 20-24 weeks |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| BMI greater than/equal to 25 | Count of Participants | Participants |
|
| OG002 |
| Metformin XR |
Metformin XR with 500 mg once a day for 2 weeks, followed by 500 mg twice a day for 2 weeks, followed by 500 mg in the AM, 1000 mg in the PM for 2 weeks, with 1000 mg twice a day as the final dose for 20 weeks MET XR: 1000 mg Metformin XR BID for 20-24 weeks |
|
|
|
| Secondary | Change in Percent Body Weight | Change in percent body weight with combination therapy compared to monotherapy from baseline to week 24 | Posted | Mean | Standard Deviation | percent weight loss from baseline | Change from baseline (time 0) to study end (24 weeks) |
|
|
|
|
| Secondary | Body Mass Index (BMI) | BMI (measure of overall adiposity) in combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | kg/m2 | 24 weeks of treatment |
|
|
|
|
| Secondary | Waist Circumference (WC) | Waist size (measure of truncal adiposity)with combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | centimeters | 24 weeks of treatment |
|
|
|
|
| Secondary | Waist- to -Hip Ratio (WHR; Measure of Central Adiposity) | Waist-to-hip ratio with combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | Ratio | 24 weeks of treatment |
|
|
|
|
| Secondary | Waist-to-height Ratio (WHtR) | Waist divided by height a( measure of central adiposity) with combination therapy compared to monotherapy after 24 weeks of therapy | Posted | Mean | Standard Deviation | ratio | 24 weeks of treatment |
|
|
|
|
| Secondary | Diastolic Blood Pressure (DBP) | Diastolic blood pressure with combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | mmHG | 24 weeks of treatment) |
|
|
|
|
| Secondary | Systolic Blood Pressure (SBP) | Systolic blood pressure with combination therapy compared to monotherapy after 24 weeks of therapy | Posted | Mean | Standard Deviation | mmHg | 24 weeks of treatment |
|
|
|
|
| Secondary | Liver Enzymes | ALT/AST ratio with combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | Ratio | 24 weeks of treatment |
|
|
|
|
| Secondary | Total Cholesterol Levels (CHOL) | Cholesterol levels with combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | mg/dL | 24 weeks of treatment |
|
|
|
|
| Secondary | Triglyceride (TRG) Levels | Triglyceride levels with combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | mg/dL | 24 weeks of treatment |
|
|
|
|
| Secondary | Fasting Blood Glucose (FBG) | Fasting blood glucose levels with combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | mg/dL | 24 weeks of treatment |
|
|
|
|
| Secondary | Mean Blood Glucose (MBG) During an OGTT | Mean blood glucose after glucose load with combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | mg/dL | 24 weeks of treatment |
|
|
|
|
| Secondary | Fasting Insulin Sensitivity (HOMA-IR) | HOMA index of insulin resistance calculated from fasting insulin and glucose with combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | Index | 24 weeks of treatment |
|
|
|
|
| Secondary | Matsuda Sensitivity Index (SI OGTT) | Surrogate measure of insulin sensitivity derived from OGTT with combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | Index | 24 weeks of treatment |
|
|
|
|
| Secondary | First Phase Insulin Secretion (IGI/HOMA-IR) | Corrected early insulin response to glucose challenge [(insulinogenic index (IGI)/ divided by fasting insulin resistance index (HOMA-IR)] with combination therapy compared to monotherapy after 24 weeks of treatment | Posted | Mean | Standard Deviation | Index | 24 weeks of treatment |
|
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 6 |
| 20 |
| EG001 | Dapaglifloxin | Dapagliflozin- 10 mg once daily before first meal for 24 weeks DAPA: 10 mg dapagliflozin QD for 20-24 weeks | 0 | 21 | 0 | 21 | 6 | 21 |
| EG002 | Metformin XR | Metformin XR with 500 mg once a day for 2 weeks, followed by 500 mg twice a day for 2 weeks, followed by 500 mg in the AM, 1000 mg in the PM for 2 weeks, with 1000 mg twice a day as the final dose for 20 weeks MET XR: 1000 mg Metformin XR BID for 20-24 weeks | 0 | 25 | 0 | 25 | 5 | 25 |
| Nausea/diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
Not provided
Not provided
| D004700 | Endocrine System Diseases |