Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Combined Liraglutide and Metformin Therapy in Women With Previous Gestational Diabetes Mellitus (GDM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01234649
Recruitment Status : Completed
First Posted : November 4, 2010
Results First Posted : July 26, 2019
Last Update Posted : July 26, 2019
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Karen Elkind-Hirsch, Woman's

Brief 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.

Condition or disease Intervention/treatment Phase
Gestational Diabetes Mellitus Type 2 Diabetes Mellitus Metabolic Syndrome Impaired Glucose Tolerance Disorder of Glucose Regulation Drug: Metformin XR plus placebo Drug: Metformin XR plus liraglutide Phase 3

Detailed Description:
Gestational diabetes is often the culmination of years of unrecognized and unmodified diabetes risk factors that lead to overt and occult clinical manifestations during pregnancy. . Despite the high and increasing rate of type 2 diabetes in Louisiana, the medical community does not have reliable estimates of the number of woman living in southern Louisiana who develop diabetes subsequent to GDM. Systematic reviews of older studies conclude that 35-60% women with gestational diabetes will develop type 2 diabetes at rates much greater than control groups who did not have glucose intolerance during pregnancy. The higher rates were in studies of particular ethnic groups in the U.S. Recently, follow-up programs elsewhere also have identified increasing rates of type 2 diabetes by 5-10 years after GDM: 9-43% type 2 diabetes in Europe and 11-21% in Asia. The frequency of type 2 diabetes is influenced by BMI, weight gain after pregnancy, family history of diabetes, fasting and postchallenge glucose levels during and after pregnancy, postpartum insulin resistance and inadequate β-cell secretion, and the need for pharmacological treatment during pregnancy. However, the risk factors are unable to predict all cases of subsequent type 2 diabetes: the biggest risk factor is a GDM pregnancy. Presently, in the literature, there are described new, more efficient methods of diabetes prevention in groups with a high risk of this disorder, which involve both, lifestyle modification and pharmacological therapies. Lifestyle intervention was found to reduce the incidence of type 2 diabetes by 58% and metformin by 31% as compared with placebo. The use of rosiglitazone in subjects with prediabetes resulted in a 60% reduction of the diabetes incidence rate. Studies are needed for optimal postpartum and long-term health of women who have had GDM. Considerable recent evidence suggests that incretin-based therapies may be useful for the treatment of DM2 because continuous administration of glucagon-like peptide 1 (GLP-1) produces substantial improvements in glucose control and ß-cell function in subjects with type 2 diabetes. Infusion of GLP-1 improves first and second-phase insulin secretion suggesting that early GLP-1 therapy may preserve ß-cell function in subjects with IGT or mild DM2. Whereas native GLP-1 has a very short half-life, the GLP-1 analogue liraglutide has a prolonged action (t1/2=13 h) suitable for once-daily injection. Liraglutide may potentially delay disease progression in GDM considering the 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 metabolic parameters in at-risk overweight/obese women with prior GDM

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 153 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Effects of Intervention With the Glucagon-like Peptide 1 (GLP-1) Analog Liraglutide Plus Metformin Versus Metformin Monotherapy in Overweight/Obese Women With Metabolic Defects and Recent History of Gestational Diabetes Mellitus (GDM)
Actual Study Start Date : August 11, 2011
Actual Primary Completion Date : April 24, 2019
Actual Study Completion Date : June 14, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Metformin XR plus liraglutide
Metformin XR plus Liraglutide Metformin extended release (XR) 500 mg qd 2 weeks 500 mg bid 2 weeks 500 mg am, 1000 mg pm- 2 weeks 1000 mg bid- 84 weeks (end study) Liraglutide - start .6 mg SC QD step up to 1.2 mg to a max dose of 1.8 mg SC QD as tolerated
Drug: Metformin XR plus liraglutide
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)
Other Name: Victoza

Active Comparator: Metformin XR plus placebo
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 -84 weeks (end study) Placebo-start 1 injection SC QD step up to a max dose as tolerated
Drug: Metformin XR plus placebo
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
Other Name: Metformin XR is generic




Primary Outcome Measures :
  1. Insulin Secretion-Sensitivity Index (IS-SI) [ Time Frame: 84 weeks of treatment ]
    IS-SI in liraglutide-metformin (LIRA-MET) therapy compared to metformin alone (PLacebo-MET)


Secondary Outcome Measures :
  1. Fasting Blood Glucose (FBG) [ Time Frame: 84 weeks of treatment ]
    Fasting glucose levels in LIRA-MET group compared with PL-MET group

  2. Mean Glucose During OGTT (MBG) [ Time Frame: 84 weeks of treatment ]
    MBG derived from average glucose measured during OGTT in LIRA-MET group compared with PL-MET group

  3. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: 84 weeks of treatment ]
    HOMA-IR, a measure of insulin resistance derived from fasting values, in LIRA-MET group compared with PL-MET group

  4. Matsuda Insulin Sensitivity Index Derived From OGTT [ Time Frame: 84 weeks of treatment ]
    OGTT- derived insulin sensitivity index in LIRA-MET group compared with PL-MET group

  5. Insulinogenic Index (IGI) /HOMA-IR [ Time Frame: 84 weeks of treatment ]
    IGI/HOMA-IR, a measure of early insulin response corrected by fasting insulin resistance, in LIRA-MET group compared with PL-MET group

  6. Absolute Body Weight [ Time Frame: 84 weeks of treatment ]
    Body weight in LIRA-MET group compared with PL-MET group

  7. Change in Body Weight From Baseline to End of Study (Expressed as % Compared to Baseline) [ Time Frame: Change from baseline (time 0) to study end (84 weeks) ]
    Change in body weight from baseline to end o f study in LIRA-MET group compared with PL-MET group. The number was derived from final weight minus baseline and normalized to a percent.

  8. Body Mass Index (BMI) [ Time Frame: 84 weeks of treatment ]
    BMI, a measure of total body adiposity, in LIRA-MET group compared with PL-MET group

  9. Waist Circumference (WC) [ Time Frame: 84 weeks of treatment ]
    Waist size (measure of truncal adiposity) with LIRA-MET compared to PL-MET

  10. Waist-to-Hip Ratio (WHR) [ Time Frame: 84 weeks of treatment ]
    Waist circumference divided by hip circumference (a measure of central adiposity) in LIRA-MET group compared with PL-MET group

  11. Waist to Height Ratio (WHtR) [ Time Frame: 84 weeks of treatment ]
    Waist circumference divided by height (measure of body fat distribution) in LIRA-MET group compared with PL-MET group

  12. Total Cholesterol (CHOL) Levels [ Time Frame: 84 weeks of treatment ]
    CHOL levels in LIRA-MET group compared with PL-MET group

  13. High Density Lipoprotein Cholesterol (HDL-C) Levels [ Time Frame: 84 weeks of treatment ]
    HDL-C levels in LIRA-MET group compared with PL-MET group

  14. Low Density Lipoprotein Cholesterol (LDL-C) Levels [ Time Frame: 84 weeks of treatment ]
    LDL-Cholesterol levels in LIRA-MET group compared with PL-MET group

  15. Triglyceride (TRG) Levels [ Time Frame: 84 weeks of treatment ]
    TRG concentrations in LIRA-MET group compared with PL-MET group

  16. Triglyceride to High Density Lipoprotein Cholesterol Ratio TRG/HDL-C) [ Time Frame: 84 weeks of treatment ]
    TRG/HDL-Cholesterol levels in LIRA-MET group compared with PL-MET group

  17. Systolic Blood Pressure [ Time Frame: 84 weeks of treatment ]
    SBP in LIRA-MET group compared with PL-MET group

  18. Diastolic Blood Pressure [ Time Frame: 84 weeks of treatment ]
    DBP in LIRA-MET group compared with PL-MET group

  19. Alanine Aminotransferase (ALT) Levels [ Time Frame: 84 weeks of treatment ]
    Hepatic enzyme, ALT, associated with insulin resistance, in LIRA-MET group compared with PL-MET group

  20. Aspartate Aminotransferase (AST) [ Time Frame: 84 weeks of treatment ]
    The hepatic marker, AST, associated with insulin resistance in LIRA-MET group compared with PL-MET group

  21. Alanine Aminotransferase /Aspartate Aminotransferase (ALT/AST) Ratio [ Time Frame: 84 weeks of treatment ]
    ALT/AST ratio, used to assess liver function in LIRA-MET group compared with PL-MET group



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01234649


Locations
Layout table for location information
United States, Louisiana
Woman's Hospital
Baton Rouge, Louisiana, United States, 70815
Sponsors and Collaborators
Woman's
Novo Nordisk A/S
Investigators
Layout table for investigator information
Principal Investigator: Karen E Elkind-Hirsch, Ph.D. Woman's Hospital, Louisiana
Study Director: Renee Harris, M.D. Woman's Hospital, Louisiana
  Study Documents (Full-Text)

Documents provided by Karen Elkind-Hirsch, Woman's:
Informed Consent Form  [PDF] September 21, 2017


Layout table for additonal information
Responsible Party: Karen Elkind-Hirsch, Scientific Director of Research, Woman's
ClinicalTrials.gov Identifier: NCT01234649    
Other Study ID Numbers: RP10-012
First Posted: November 4, 2010    Key Record Dates
Results First Posted: July 26, 2019
Last Update Posted: July 26, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Karen Elkind-Hirsch, Woman's:
gestational diabetes mellitus
type 2 diabetes mellitus
metabolic dysfunction
impaired fasting glucose
impaired glucose tolerance
incretin mimetic
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes, Gestational
Diabetes Mellitus
Diabetes Mellitus, Type 2
Metabolic Syndrome
Glucose Intolerance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin Resistance
Hyperinsulinism
Pregnancy Complications
Hyperglycemia
Metformin
Liraglutide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists