Diabetes Prevention in Women After GDM Who Are at High-risk Clinical Trial
— DAPA-GDMOfficial title:
A Randomized Study Evaluating Dapagliflozin and Metformin, Alone and in Combination, in Overweight Women With a Recent History of Gestational Diabetes Mellitus: Effects on Anthropometric Measurements and Cardiometabolic Abnormalities
| Verified date | June 2019 |
| Source | Woman's |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 69 |
| Est. completion date | March 13, 2019 |
| Est. primary completion date | February 13, 2019 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Female |
| Age group | 18 Years to 45 Years |
| Eligibility |
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 - postpartum metabolic abnormalities determined by a 75 g oral glucose tolerance test (Inclusive of prior GDM women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT) postpartum) - Completed lactation - Using adequate contraception during study period unless sterilized - Written consent for participation in the study Exclusion Criteria: - Cholestasis during the past pregnancy - Any hepatic diseases in the past (viral hepatitis, toxic hepatic damage, jaundice of unknown etiology), gallstones, abnormal liver function tests or renal impairment (elevated serum creatinine levels or abnormal creatinine clearance - Presence of significant systemic disease, heart problems including congestive heart failure, history of pancreatitis, or diabetes mellitus (Type 1 or 2) - Renal impairment (e.g., serum creatinine levels =1.4 mg/dL for women, or eGFR <60) - Significantly elevated triglyceride levels (fasting triglyceride > 400 mg %) - Untreated or poorly controlled hypertension (sitting blood pressure >160/95mm Hg) - Prior history of a malignant disease requiring chemotherapy - Known hypersensitivity or contraindications to use of insulin sensitizers such as metformin or thiazolidinediones - History of hypersensitivity reaction to dapagliflozin or other SGLT2 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions) - Current use of metformin, thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors or weight loss medications (prescription or OTC) - Uncontrolled thyroid disease (documented normal TSH) or hyperprolactinemia - Liver enzymes (serum alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] ) levels exceeding more than twice normal lab values - Use of drugs known to exacerbate glucose tolerance - History of diabetes or prior use of medications to treat diabetes except GDM - Currently lactating - Eating disorders (anorexia, bulimia) or gastrointestinal disorders - Suspected pregnancy (documented negative serum pregnancy test within 72 hours before first dose of study drug), desiring pregnancy in next 6 months, breastfeeding, or known pregnancy in last 2 months - Active or prior history of substance abuse (smoke or tobacco use within past 3 years) or significant intake of alcohol or history of alcoholism - Patient not willing to use adequate contraception during study period and up to 4 weeks after last dose of study drug (unless sterilized). - Debilitating psychiatric disorder such as psychosis or neurological condition that might confound outcome variables - Inability or refusal to comply with protocol - Not currently participating or having participated in an experimental drug study in previous three months |
| Country | Name | City | State |
|---|---|---|---|
| United States | Woman's Hospital | Baton Rouge | Louisiana |
| Lead Sponsor | Collaborator |
|---|---|
| Woman's | AstraZeneca |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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) | |
| Secondary | 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) | |
| Secondary | Body Mass Index (BMI) | BMI (measure of overall adiposity) in combination therapy compared to monotherapy after 24 weeks of treatment | 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 | 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 | 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 | 24 weeks of treatment | |
| Secondary | Diastolic Blood Pressure (DBP) | Diastolic blood pressure with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment) | |
| Secondary | Systolic Blood Pressure (SBP) | Systolic blood pressure with combination therapy compared to monotherapy after 24 weeks of therapy | 24 weeks of treatment | |
| Secondary | Liver Enzymes | ALT/AST ratio with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment | |
| Secondary | Total Cholesterol Levels (CHOL) | Cholesterol levels with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment | |
| Secondary | Triglyceride (TRG) Levels | Triglyceride levels with combination therapy compared to monotherapy after 24 weeks of treatment | 24 weeks of treatment | |
| Secondary | Fasting Blood Glucose (FBG) | Fasting blood glucose levels with combination therapy compared to monotherapy after 24 weeks of treatment | 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 | 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 | 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 | 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 | 24 weeks of treatment |