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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

NCTNCT01234649 (opens ClinicalTrials.gov in a new tab)Other idRP10-012
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
153 participants (actual)
Sponsor
Woman's · Other
Design
Randomized · Triple masking
Countries
1 country

United States

Start
11 Aug 2011
Primary completion
24 Apr 2019
Completion
14 Jun 2019
First posted
4 Nov 2010 (estimated)
Last update posted
26 Jul 2019
Conditions
Gestational Diabetes Mellitus · Type 2 Diabetes Mellitus · Metabolic Syndrome · Impaired Glucose Tolerance · Disorder of Glucose Regulation

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20122014201620182020
  1. Ph 3

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

    NCT01234649

    11 Aug 2011 to 14 Jun 2019

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • Metformin XR plus placeboDrug
  • Metformin XR plus liraglutideDrug

Arms2

  • 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

  • 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

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Insulin Secretion-Sensitivity Index (IS-SI)

    Time frame · 84 weeks of treatment

    Registry description

    IS-SI in liraglutide-metformin (LIRA-MET) therapy compared to metformin alone (PLacebo-MET)

Secondary outcomes(20)

  1. Fasting Blood Glucose (FBG)

    Time frame · 84 weeks of treatment

    Registry description

    Fasting glucose levels in LIRA-MET group compared with PL-MET group

  2. Mean Glucose During OGTT (MBG)

    Time frame · 84 weeks of treatment

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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)

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    LDL-Cholesterol levels in LIRA-MET group compared with PL-MET group

  15. Triglyceride (TRG) Levels

    Time frame · 84 weeks of treatment

    Registry description

    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

    Registry description

    TRG/HDL-Cholesterol levels in LIRA-MET group compared with PL-MET group

  17. Systolic Blood Pressure

    Time frame · 84 weeks of treatment

    Registry description

    SBP in LIRA-MET group compared with PL-MET group

  18. Diastolic Blood Pressure

    Time frame · 84 weeks of treatment

    Registry description

    DBP in LIRA-MET group compared with PL-MET group

  19. Alanine Aminotransferase (ALT) Levels

    Time frame · 84 weeks of treatment

    Registry description

    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

    Registry description

    The hepatic marker, AST, associated with insulin resistance in LIRA-MET group compared with PL-MET group

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· 84 weeks of treatment

Insulin Secretion-Sensitivity Index (IS-SI)

GroupValue (index)Spread
Metformin XR Plus Liraglutide418.4387
Metformin XR Plus Placebo333206
Secondary and other outcome results(7)
Secondary outcomeMean· 84 weeks of treatment

Fasting Blood Glucose (FBG)

GroupValue (mg/dL)Spread
Metformin XR Plus Liraglutide906.4
Metformin XR Plus Placebo91.78.4
Secondary outcomeMean· 84 weeks of treatment

Mean Glucose During OGTT (MBG)

GroupValue (mg/dL)Spread
Metformin XR Plus Liraglutide121.620.8
Metformin XR Plus Placebo118.818.9
Secondary outcomeMean· 84 weeks of treatment

Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)

GroupValue (index)Spread
Metformin XR Plus Liraglutide2.21.4
Metformin XR Plus Placebo2.451.5
Secondary outcomeMean· 84 weeks of treatment

Matsuda Insulin Sensitivity Index Derived From OGTT

GroupValue (index)Spread
Metformin XR Plus Liraglutide5.92.9
Metformin XR Plus Placebo5.43.2
Secondary outcomeMean· 84 weeks of treatment

Insulinogenic Index (IGI) /HOMA-IR

GroupValue (index)Spread
Metformin XR Plus Liraglutide0.81.14
Metformin XR Plus Placebo0.620.38
Secondary outcomeMean· 84 weeks of treatment

Absolute Body Weight

GroupValue (kilograms)Spread
Metformin XR Plus Liraglutide94.218.6
Metformin XR Plus Placebo91.320
Secondary outcomeMean· Change from baseline (time 0) to study end (84 weeks)

Change in Body Weight From Baseline to End of Study (Expressed as % Compared to Baseline)

GroupValue (percent change in weight from baseline)Spread
Metformin XR Plus Liraglutide-7.21.3
Metformin XR Plus Placebo-3.11.4

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Metformin XR Plus LiraglutideMetformin 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 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)0 / 780 / 7830 / 78
Metformin XR Plus PlaceboMetformin 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 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 tolerated0 / 750 / 7514 / 75

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2020

6 results

Postpartum treatment with liraglutide in combination with metformin versus metformin monotherapy to improve metabolic status and reduce body weight in overweight/obese women with recent gestational diabetes: A double-blind, randomized, placebo-controlled study.

Elkind-Hirsch et al. 2020Journal of diabetes and its complicationscited by 30

PMID 32046931DOI 10.1016/j.jdiacomp.2020.107548PUB-32046931

Full text at the publisher6 results
Publisher pageSee results (6)

Eligibility

Who could join, as posted.

Sex
Female
Age
from 18 Years up to 45 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
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

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