Gestational Diabetes: Insulin or Oral Hypoglycemic Agents? (DG5)
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.
|Gestational Diabetes Mellitus||Drug: Insulin Drug: Metformin, glyburide and insulin||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Gestational Diabetes Mellitus: Insulin or Oral Hypoglycemic Agents?|
- Glycemic control [ Time Frame: 36 and 37th week of gestation ]Mean of the capillary glycemic control at 36 and 37th week of gestation.
- Acceptability of the treatment [ Time Frame: 8-12 weeks after delivery ]
|Study Start Date:||August 2010|
|Study Completion Date:||September 2014|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Insulin
Rapid acting insulin and long acting 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).
Experimental: Oral Hypoglycemic Agents
Metformin + glyburide + insulin if needed
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01215331
|Centre de recherche clinique du CHUS|
|Sherbrooke, Quebec, Canada, J1H 5N4|
|Principal Investigator:||Jean-Luc Ardilouze, MD, PhD||Université de Sherbrooke|