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      A review of current treatment strategies for gestational diabetes mellitus

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          Abstract

          Approximately 90% of diabetes cases in pregnant women are considered gestational diabetes mellitus (GDM). It is well known that uncontrolled glucose results in poor pregnancy outcomes in both the mother and fetus. Worldwide there are many guidelines with recommendations for appropriate management strategies for GDM once lifestyle modifications have been instituted and failed to achieve control. The efficacy and particularly the safety of other treatment modalities for GDM has been the source of much debate in recent years. Studies that have demonstrated the safety and efficacy of both glyburide and metformin in the management of patients with GDM will be reviewed. There is a lack of evidence with other oral and injectable non-insulin agents to control blood glucose in GDM. The role of insulin will be discussed, with emphasis on insulin analogs. Ideal patient characteristics for each treatment modality will be reviewed. In addition, recommendations for postpartum screening of patients will be described as well as recommendations for use of agents to manage subsequent type 2 diabetes in patients who are breastfeeding.

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          Most cited references74

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          Metformin versus insulin for the treatment of gestational diabetes.

          Metformin is a logical treatment for women with gestational diabetes mellitus, but randomized trials to assess the efficacy and safety of its use for this condition are lacking. We randomly assigned 751 women with gestational diabetes mellitus at 20 to 33 weeks of gestation to open treatment with metformin (with supplemental insulin if required) or insulin. The primary outcome was a composite of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score less than 7, or prematurity. The trial was designed to rule out a 33% increase (from 30% to 40%) in this composite outcome in infants of women treated with metformin as compared with those treated with insulin. Secondary outcomes included neonatal anthropometric measurements, maternal glycemic control, maternal hypertensive complications, postpartum glucose tolerance, and acceptability of treatment. Of the 363 women assigned to metformin, 92.6% continued to receive metformin until delivery and 46.3% received supplemental insulin. The rate of the primary composite outcome was 32.0% in the group assigned to metformin and 32.2% in the insulin group (relative risk, 0.99 [corrected]; 95% confidence interval, 0.80 [corrected] to 1.23 [corrected]). More women in the metformin group than in the insulin group stated that they would choose to receive their assigned treatment again (76.6% vs. 27.2%, P<0.001). The rates of other secondary outcomes did not differ significantly between the groups. There were no serious adverse events associated with the use of metformin. In women with gestational diabetes mellitus, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin. The women preferred metformin to insulin treatment. (Australian New Zealand Clinical Trials Registry number, 12605000311651.). Copyright 2008 Massachusetts Medical Society.
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            Practice Bulletin No. 137: Gestational diabetes mellitus.

            (2013)
            Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Debate continues to surround both the diagnosis and treatment of GDM despite several recent large-scale studies addressing these issues. The purpose of this document is to 1) provide a brief overview of the understanding of GDM, 2) provide management guidelines that have been validated by appropriately conducted clinical research, and 3) identify gaps in current knowledge toward which future research can be directed.
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              Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis

              Objective To summarize short term outcomes in randomized controlled trials comparing glibenclamide or metformin versus insulin or versus each other in women with gestational diabetes requiring drug treatment. Design Systematic review and meta-analysis. Eligibility criteria for selecting studies Randomized controlled trials that fulfilled all the following: (1) published as full text; (2) addressed women with gestational diabetes requiring drug treatment; (3) compared glibenclamide v insulin, metformin v insulin, or metformin v glibenclamide; and (4) provided information on maternal or fetal outcomes. Data sources Medline, CENTRAL, and Embase were searched up to 20 May 2014. Outcomes measures We considered 14 primary outcomes (6 maternal, 8 fetal) and 16 secondary (5 maternal, 11 fetal) outcomes. Results We analyzed 15 articles, including 2509 subjects. Significant differences for primary outcomes in glibenclamide v insulin were obtained in birth weight (mean difference 109 g (95% confidence interval 35.9 to 181)), macrosomia (risk ratio 2.62 (1.35 to 5.08)), and neonatal hypoglycaemia (risk ratio 2.04 (1.30 to 3.20)). In metformin v insulin, significance was reached for maternal weight gain (mean difference −1.14 kg (−2.22 to −0.06)), gestational age at delivery (mean difference −0.16 weeks (−0.30 to −0.02)), and preterm birth (risk ratio 1.50 (1.04 to 2.16)), with a trend for neonatal hypoglycaemia (risk ratio 0.78 (0.60 to 1.01)). In metformin v glibenclamide, significance was reached for maternal weight gain (mean difference −2.06 kg (−3.98 to −0.14)), birth weight (mean difference −209 g (−314 to −104)), macrosomia (risk ratio 0.33 (0.13 to 0.81)), and large for gestational age newborn (risk ratio 0.44 (0.21 to 0.92)). Four secondary outcomes were better for metformin in metformin v insulin, and one was worse for metformin in metformin v glibenclamide. Treatment failure was higher with metformin than with glibenclamide. Conclusions At short term, in women with gestational diabetes requiring drug treatment, glibenclamide is clearly inferior to both insulin and metformin, while metformin (plus insulin when required) performs slightly better than insulin. According to these results, glibenclamide should not be used for the treatment of women with gestational diabetes if insulin or metformin is available. Systematic review registration NCT01998113
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                Author and article information

                Journal
                Drugs Context
                Drugs Context
                DIC
                Drugs in Context
                Just Medical Media Limited
                1745-1981
                1740-4398
                2015
                15 July 2015
                : 4
                : 212282
                Affiliations
                Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Auburn, AL, USA
                Author notes
                Correspondence: Kristi W Kelley, PharmD, BCPS, CDE, BC-ADM; Continuity of Care Clinic, Trinity Medical Center, 840 Montclair Road, Suite 122, Birmingham, Alabama 35213, USA. watsokm@ 123456auburn.edu

                Correct attribution: Copyright © 2015 Kelley KW, Carroll DG, Meyer A. http://dx.doi.org/10.7573/dic.212282. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 3.0.

                Provenance: Invited; externally peer reviewed

                Peer review comments to author: 19 May 2015

                Drugs in Context is published by Just Medical Media Ltd. Registered office: Undermount, Rydal, Ambleside, Cumbria, LA22 9LT, UK

                Just Medical Media Limited is registered in England Number 6891187. VAT GB 945 1713 22

                For all manuscript and submissions enquiries, contact Julia Savory, Head of Digital Publishing and Submissions Management julia@ 123456justmedicalmedia.com

                For all permissions, rights, and reprints, contact Stephen I’Anson, Commercial Director steve@ 123456justmedicalmedia.com

                Article
                dic-4-212282
                10.7573/dic.212282
                4509429
                26213555
                8c816fea-c1de-4041-92a2-bc459eb6b590
                Copyright © 2015 Kelley KW, Carroll DG, Meyer A.

                Distributed under the terms of the Creative Commons License Deed CC BY NC ND 3.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

                History
                : 02 May 2015
                Categories
                Review

                gestational diabetes,fetal macrosomia,glyburide,hypoglycemia,hypoglycemic agents,insulin,long-acting insulin,short-acting insulin,metformin,postnatal care

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