Intervention: Dapagliflozin
Trial phase: Phase 3
ATC code: A10BD15 | A10BD21 | A10BD25 | A10BK01
SMILES: CCOc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)ccc2Cl)cc1
Sex: Female
Age groups: Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 25
Group description: 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
Eligibility criteria:
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