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

NCT01234649 | Completed Phase 3 Results DMC

• 1 other identifier: RP10-012
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 1

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.

Conditions

Gestational Diabetes Mellitus; Type 2 Diabetes Mellitus; Metabolic Syndrome; Impaired Glucose Tolerance; Disorder of Glucose Regulation

Keywords

gestational diabetes mellitus; type 2 diabetes mellitus; metabolic dysfunction; impaired fasting glucose; impaired glucose tolerance; incretin mimetic

Outcome Measures

Primary Outcomes (1)

• Insulin Secretion-Sensitivity Index (IS-SI)

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

  84 weeks of treatment

Secondary Outcomes (21)

• Fasting Blood Glucose (FBG)

  84 weeks of treatment

• Mean Glucose During OGTT (MBG)

  84 weeks of treatment

• Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)

  84 weeks of treatment

• Matsuda Insulin Sensitivity Index Derived From OGTT

  84 weeks of treatment

• Insulinogenic Index (IGI) /HOMA-IR

  84 weeks of treatment

Study Arms (2)

Metformin XR plus liraglutide

EXPERIMENTAL

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 plus placebo

ACTIVE COMPARATOR

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

Interventions

Metformin XR plus placebo DRUG

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

Also known as: Metformin XR is generic

Metformin XR plus placebo

Metformin XR plus liraglutide DRUG

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)

Also known as: Victoza

Metformin XR plus liraglutide

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Woman's: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Woman's Hospital

Baton Rouge, Louisiana, 70815, United States

Location

Related Publications (1)

• Elkind-Hirsch KE, Shaler D, Harris R. 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. J Diabetes Complications. 2020 Apr;34(4):107548. doi: 10.1016/j.jdiacomp.2020.107548. Epub 2020 Feb 1.

  PMID: 32046931 DERIVED

MeSH Terms

Conditions

Diabetes, Gestational; Diabetes Mellitus, Type 2; Metabolic Syndrome; Glucose Intolerance

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Insulin Resistance; Hyperinsulinism; Hyperglycemia

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

A large percentage of patients did not complete the trial with the greatest loss from first study visit to second visit. A greater loss was seen initially in the metformin only group.

Results Point of Contact

• Title: Dr Karen Elkind-Hirsch
• Organization: Woman's Hospital

karen.elkind-hirsch@womans.org

225 231-5275

Study Officials

• Karen E Elkind-Hirsch, Ph.D.

  Woman's Hospital, Louisiana

  PRINCIPAL INVESTIGATOR

• Renee Harris, M.D.

  Woman's Hospital, Louisiana

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientific Director of Research

Study Record Dates

• First Submitted: November 3, 2010
• First Posted: November 4, 2010
• Study Start: August 11, 2011
• Primary Completion: April 24, 2019
• Study Completion: June 14, 2019
• Last Updated: July 26, 2019
• Results First Posted: July 26, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)