Gestational Diabetes: Insulin or Oral Hypoglycemic Agents?

NCT ID: NCT01215331

Last Updated: 2018-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2016-05-31

Brief Summary

Gestational diabetes mellitus takes place in 2 steps. First, it is the consequence of insulin resistance due to the modifications of the pregnancy hormonal environment, and second, of the deficiency of the beta cells of the pancreas to respond by a sufficient insulin secretion. This physiopathology is closely connected to the one of type 2 diabetes. Insulin, indeed, can remedy these 2 etiologies, but it is logical to think about using oral hypoglycemic agents which have been created to treat them: they are a natural choice because they improve insulin sensitivity (metformin, a biguanide) or insulin secretion (glyburide, a sulfonylurea). It also seems natural to use them in combination, glyburide being added to metformin if needed.

OUR GENERAL RESEARCH HYPOTHESIS IS THAT: in pregnant women with gestational diabetes mellitus, using both oral hypoglycemic agents (glyburide added to metformin if needed) allows a glycemic control comparable to the one obtained with insulin, but with a better acceptability from women and a better health status, diabetes treatment satisfaction and well-being and a reduced postnatal depression.

Conditions

Gestational Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Insulin

Rapid acting insulin and long acting insulin

Group Type: ACTIVE_COMPARATOR

Insulin

Intervention Type: DRUG

Insulins most commonly used during pregnancy by our group are rapid acting insulins and long acting human insulins (long acting analogs are not authorized in pregnancy). An ultra-fast acting insulin will be started before a meal (1, 2 or 3 meals) at 4-6 IU (according to the weight) if the glycemic value 2 hours after this meal is ≥ 6.7 mmol/L in 50% of cases. It will be increased by 2 units every 2 days until obtaining the aimed objectives. Long acting insulin will be started at 4-6 units at bedtime if the glycemic value before breakfast is ≥ 5.3 mmol/L in 50% of cases, and it will be increased by 2 units every 2 days until reaching the objective. A combination of both insulins could be necessary (maximum of 4 injections per day).

Oral Hypoglycemic Agents

Metformin + glyburide + insulin if needed

Group Type: EXPERIMENTAL

Metformin, glyburide and insulin

Intervention Type: DRUG

Metformin (tablets of 500 mg) will be started at 250 mg/day x 1 day, and increased thereafter by 250 mg per day every 3 days until obtaining an adequate glycemic control. If metformin does not prove its effect at a dose of 750 mg, or if the side effects (mainly gastric) command to slow down or not to increase the posology, glyburide will be added.

Glyburide (tablets of 5 mg) will be started at a dose of 2.5 mg and will be increased by 2.5 mg every 3 days until obtaining an adequate glycemic control. The maximal dose in the study will bw 10 mg. It corresponds to the half of the maximal dose recommended in Canada.

Treatment failure is defined as glycemia above the Canadian Diabetes Association therapeutic objectives in spite of maximal doses or whether the doses can not be increased because of side effects. Insulin will be added to oral hypoglycemic agents.

Interventions

Insulin

Insulins most commonly used during pregnancy by our group are rapid acting insulins and long acting human insulins (long acting analogs are not authorized in pregnancy). An ultra-fast acting insulin will be started before a meal (1, 2 or 3 meals) at 4-6 IU (according to the weight) if the glycemic value 2 hours after this meal is ≥ 6.7 mmol/L in 50% of cases. It will be increased by 2 units every 2 days until obtaining the aimed objectives. Long acting insulin will be started at 4-6 units at bedtime if the glycemic value before breakfast is ≥ 5.3 mmol/L in 50% of cases, and it will be increased by 2 units every 2 days until reaching the objective. A combination of both insulins could be necessary (maximum of 4 injections per day).

Intervention Type: DRUG

Metformin, glyburide and insulin

Metformin (tablets of 500 mg) will be started at 250 mg/day x 1 day, and increased thereafter by 250 mg per day every 3 days until obtaining an adequate glycemic control. If metformin does not prove its effect at a dose of 750 mg, or if the side effects (mainly gastric) command to slow down or not to increase the posology, glyburide will be added.

Glyburide (tablets of 5 mg) will be started at a dose of 2.5 mg and will be increased by 2.5 mg every 3 days until obtaining an adequate glycemic control. The maximal dose in the study will bw 10 mg. It corresponds to the half of the maximal dose recommended in Canada.

Treatment failure is defined as glycemia above the Canadian Diabetes Association therapeutic objectives in spite of maximal doses or whether the doses can not be increased because of side effects. Insulin will be added to oral hypoglycemic agents.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• women,
• age ≥ 18 yrs,
• with gestational diabetes at 24-28 weeks (Canadian Diabetes Association (CDA) criteria),
• who need a pharmacological treatment following the failure of the diet and exercise,
• to understand and read French or English.

Exclusion Criteria

• known type 1 or type 2 diabetes,
• treatment interfering with glucose metabolism,
• allergies to one of the components of the treatment,
• hepatic or hematologic diseases.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fonds de la Recherche en Santé du Québec

OTHER_GOV

Sponsor Role: collaborator

Université de Sherbrooke

OTHER

Sponsor Role: lead

Responsible Party

Jean-Luc Ardilouze

Endocrinologist, researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jean-Luc Ardilouze, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Université de Sherbrooke

Locations

Centre de recherche clinique du CHUS

Sherbrooke, Quebec, Canada

Countries

Canada

Other Identifiers

08-057

Identifier Type: -

Identifier Source: org_study_id