Combined Liraglutide and Metformin Therapy in Women With Previous Gestational Diabetes Mellitus (GDM)
Condition: Gestational Diabetes Mellitus; Type 2 Diabetes Mellitus; Metabolic Syndrome; Impaired Glucose Tolerance; Disorder of Glucose Regulation
MeSH terms: Diabetes, Gestational; Diabetes Mellitus; Diabetes Mellitus, Type 2; Metabolic Syndrome; Glucose Intolerance
Intervention: Metformin XR plus placebo; Metformin XR plus liraglutide
Intervention description: Metformin plus Placebo Metformin 500 mg qd 2 weeks 500 mg bid 2 weeks 500 mg am, 1000 mg pm- 2 weeks 1000 mg bid -98 weeks (end study) Placebo-start 1 injection SC QD step up to a max dose as tolerated; Metformin XR-500 qd for 2 weeks, 500 mg bid 2 weeks; 500 mg am, 1000 mg pm- 2 weeks - 1000 bid final dose Liraglutide- start 0.6 mg SC QD step up to 1.2 mg to a max dose of 1.8 mg SC QD as tolerated during the 4-wk non-forced dose-escalation period ( maximum allowed dose of 1.8 mg SC QD)
Intervention MeSH terms: Metformin; Liraglutide
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 153.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: gestational diabetes mellitus; type 2 diabetes mellitus; metabolic dysfunction; impaired fasting glucose; impaired glucose tolerance; incretin mimetic

Summary:

      A diagnosis of gestational diabetes mellitus (GDM)has significant implications for the future
      health of the mother. GDM is often the culmination of years of unrecognized and unmodified
      diabetes risk factors that lead to overt and occult clinical manifestations during pregnancy.
      Systematic reviews of older studies conclude that 35-60% women with gestational diabetes will
      develop type 2 diabetes (DM2) at rates much greater than control groups who did not have
      glucose intolerance during pregnancy. Liraglutide may potentially delay disease progression
      in GDM considering the beta -(ß-)cell function improvement in DM2 and ß-cell mass shown to
      increase in animal models. This study will examine if the addition of liraglutide to
      metformin therapy is more effective than metformin alone in improving insulin sensitivity and
      normalizing insulin secretion in at-risk overweight/obese women with prior GDM.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult female 18 years to 45 years of age who experienced GDM within 52 weeks of index
             pregnancy

          -  Actual BMI >25 kg/ m2

          -  Written consent for participation in the study

          -  Patient completed lactation

          -  Dysglycemia (impaired fasting glucose [IFG}, impaired glucose tolerance [IGT} or
             IFG/IGT) and/or ß-cell dysfunction postpartum requiring pharmacological intervention
             (except type 1 or 2 diabetes)

        Exclusion Criteria:

        Personal or family history of medullary thyroid carcinoma or in patients with Multiple
        Endocrine Neoplasia syndrome type 2

          -  History of pancreatitis

          -  Significant cardiovascular, cerebrovascular, renal, or hepatobiliary diseases in the
             past (viral hepatitis, toxic hepatic damage, jaundice of unknown etiology)

          -  Serum liver enzymes (AST and/or ALT levels) exceeding more than twice normal
             laboratory values

          -  Uncontrolled hypertension (systolic blood pressure>150 mm Hg and/or diastolic blood
             pressure >90 mm Hg)

          -  Fasting serum triglycerides ≥800 mg/dl at screening. Lipid-lowering medications must
             have been maintained at the same dose for 3 months prior to enrollment

          -  Hematological profiles considered to be clinically significant

          -  Cholestasis during the past pregnancy

          -  Presence of contradictions for GLP-1 receptor agonist or metformin administration such
             as allergy or hypersensitivity

          -  Current use of metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors or
             GLP-1 receptor agonist medications.

          -  Use of drugs known to exacerbate glucose tolerance.

          -  Use of prescription or over-the-counter weight-loss drugs

          -  Diabetes postpartum or history of diabetes or prior use of medications to treat
             diabetes except gestational diabetes

          -  Creatinine clearance less than 60 ml/min

          -  History or currently undergoing chemotherapy or radiotherapy for cancer

          -  Pregnancy planned during the coming two years

          -  Currently breastfeeding

          -  Exclusion criteria include any condition, which in the opinion of the investigator
             would place the subject at increased risk or otherwise make the subject unsuitable for
             participation in the study