Phase 3
N=153
Combined Liraglutide and Metformin Therapy in Women With Previous Gestational Diabetes Mellitus (GDM)
Gestational Diabetes Mellitus · Type 2 Diabetes Mellitus · Metabolic Syndrome · Impaired Glucose Tolerance · Disorder of Glucose Regulation
Bottom Line
View on ClinicalTrials.gov: NCT01234649 ↗Enrolled (actual)
153
Serious AEs
0.0%
Results posted
Jul 2019
Primary outcome: Primary: Insulin Secretion-Sensitivity Index (IS-SI) — 418.4; 333 index — p=<0.04
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Metformin XR plus placebo (Drug); Metformin XR plus liraglutide (Drug)
- Age
- Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Woman's
- Primary completion
- Apr 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Insulin Secretion-Sensitivity Index (IS-SI) |
418.4; 333 | <0.04 sig |
| SECONDARY Fasting Blood Glucose (FBG) |
90; 91.7 | <.005 sig |
| SECONDARY Mean Glucose During OGTT (MBG) |
121.6; 118.8 | <0.011 sig |
| SECONDARY Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) |
2.2; 2.45 | >0.05 |
| SECONDARY Matsuda Insulin Sensitivity Index Derived From OGTT |
5.9; 5.4 | <0.03 sig |
| SECONDARY Insulinogenic Index (IGI) /HOMA-IR |
0.8; 0.62 | >0.05 |
| SECONDARY Absolute Body Weight |
94.2; 91.3 | <0.048 sig |
| SECONDARY Change in Body Weight From Baseline to End of Study (Expressed as % Compared to Baseline) |
-7.2; -3.1 | <0.04 sig |
| SECONDARY Body Mass Index (BMI) |
33.8; 32.8 | <0.047 sig |
| SECONDARY Waist Circumference (WC) |
94.3; 95.3 | <0.023 sig |
| SECONDARY Waist-to-Hip Ratio (WHR) |
.81; .81 | >0.05 |
| SECONDARY Waist to Height Ratio (WHtR) |
.56; .57 | 0.042 sig |
| SECONDARY Total Cholesterol (CHOL) Levels |
183.7; 183.8 | >0.05 |
| SECONDARY High Density Lipoprotein Cholesterol (HDL-C) Levels |
51; 48.7 | >0.05 |
| SECONDARY Low Density Lipoprotein Cholesterol (LDL-C) Levels |
110; 107 | >0.05 |
| SECONDARY Triglyceride (TRG) Levels |
120; 125 | <0.046 sig |
| SECONDARY Triglyceride to High Density Lipoprotein Cholesterol Ratio TRG/HDL-C) |
2.56; 2.95 | <0.049 sig |
| SECONDARY Systolic Blood Pressure |
122; 123 | >0.05 |
| SECONDARY Diastolic Blood Pressure |
77.6; 77 | >0.05 |
| SECONDARY Alanine Aminotransferase (ALT) Levels |
32.3; 31 | >0.05 |
| SECONDARY Aspartate Aminotransferase (AST) |
27; 28 | >0.05 |
| SECONDARY Alanine Aminotransferase /Aspartate Aminotransferase (ALT/AST) Ratio |
1.2; 1.18 | >0.05 |
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
Data sourced from ClinicalTrials.gov (NCT01234649). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.