Which oral hypoglycaemic for gestational diabetes?
BMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h177 (Published 21 January 2015) Cite this as: BMJ 2015;350:h177
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The editorial comment on the effectiveness of metformin over glibenclamide seems to be based on the current study by Balsells M et al (1) and other studies on the subject. The clear role, based on the meta-analysis report should be taken with caution. Several other studies, otherwise have found that metformin is inferior to glibenclamide (2,3). Moore et al observed that , the failure rate of metformin was 2.1 times higher than the failure rate of glyburide when used in the management of gestational diabetes (95% confidence interval 1.2-3.9) (3).
Holt RI et al are of the opinion that insulin has been the mainstay in the management of gestational diabetes when lifestyle measures are unable to control glycaemic levels (4). They have also reported that Glibenclamide effectively lowers blood glucose among women with gestational diabetes, and possibly has a lower treatment failure rate than metformin. The American College of Obstetrics and Gynecology and the UK National Institute of Health and Care Excellence (NICE) have recommended that either of the drugs metformin or glibenclamide can be used to treat gestational diabetes. However, the conflicting nature of the available reports stress the need for a uniform study design, similarity in dosage, timing of intake of medication with meals without meals, insulin resistance status etc.
References
1. Balsells M, García-Patterson A, Sola I, Roque M, Gich I, Corcoy R. Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis. BMJ2015;350:h102.
2. Wilson C. Diabetes: Gestational diabetes: glibenclamide or metformin? Nature Reviews Endocrinology 6, 183 (April 2010) | doi:10.1038/nrendo.2010.12.
3. Moore LE, Clokey D, Rappaport VJ, Curet LB.Metformin compared with glyburide in gestational diabetes: a randomized controlled trial. Obstet Gynecol. 2010 Jan;115(1):55-9. doi: 10.1097/AOG.0b013e3181c52132.
Authors
Reeta Devi,
Assistant Professor, School of Health Sciences
IGNOU, New Delhi
Mongjam Meghachandra Singh
Professor
Department of Community Medicine
Maulana Azad Medical College, New Delhi
Bimla Kapoor
Ex-Director and Professor,School of Health Sciences
IGNOU, New Delhi
Competing interests: No competing interests
Re: Which oral hypoglycaemic for gestational diabetes?
To the editor:
I thank Professor Devi and colleagues for their comments.
A meta-analysis seeks to minimize differences in methodology among different studies comparing the same outcome so that valid inferences based on larger numbers of subjects can be made.
Among the difficulties posed in such analyses are differences in definitions of independent and outcome variables and criteria for intervention. In the paper by Balsells, et al1 only two studies were available for direct comparisons of glibenclamide and metformin for women with gestational diabetes2,3. As was indicated by the authors, these differed in key variables. Gestational diabetes was defined in each by different criteria. The maternal glucose concentrations selected to indicate pharmacologic treatment were different. Furthermore, data for some important outcomes (eg severe maternal hypoglycemia, large for gestational age) were available in only one of the two studies. Despite these differences, the authors found significantly less maternal weight gain and measures of birth weight and fetal overgrowth among those treated with metformin. Significantly more patients receiving metformin required the addition of insulin than did those using glibenclamide in the study in which the maximum metformin dose was 2000 mg per day3. However, no statistically significant differences in the requirement for additional insulin were found in the study in which the threshold for the addition of insulin to metformin was 2500 mg2.
It is possible that the difference in dose thresholds used to indicate the addition of insulin explains the difference in failure rates between these two studies. It must be noted that the largest randomized controlled trial comparing metformin alone with insulin alone reported that 46% of women in the former group required insulin supplementation. The maximum dose of metformin in this study was also 2500 mg4. I agree that inferences made from only two studies should be regarded with cautious skepticism. A well-powered randomized controlled trial comparing glibenclamide with metformin might provide needed clarification of the appropriate use of either drug in the treatment of gestational diabetes.
1. Balsells M, Garcia-Patterson A, Sola I, Roque M, Gich I, Corcoy R. Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis. BMJ 2015;350:h102.
2. Silva JC, Fachin DR, Coral ML, Bertini AM. Perinatal impact of the use of metformin and glyburide for the treatment of gestational diabetes mellitus. J Perinat Med 2012;40:225-8.
3. Moore LE, Clokey D, Rappaport VJ, Curet LB. Metformin compared with glyburide in gestational diabetes: a randomized controlled trial. Obstet Gynecol 2010;115:55-9.
4. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med 2008;358:2003-15.
Very truly yours,
David A Sacks MD
Competing interests: No competing interests