Metformin Radiosensitizing Effect on Hypoxic Oral Squamous Cell Carcinoma Cells by GAPDH and TAGLN2.

OBJECTIVE: Tumor hypoxia is associated with a poorer prognosis in cancer patients and can diminish the efficacy of radiation therapy (RT). This study investigates the potential of metformin to enhance radiosensitivity in hypoxic cancer cells. METHODS: Preliminary experiments were conducted to validate the impact of hypoxia on radiation response. Reactive oxygen species (ROS) levels, cell migration, and cell death were assessed in hypoxic, radiated cells treated with metformin. Proteomic and ontological analyses were employed to identify molecular targets associated with the radiosensitizing effect of metformin. Proteomic and ontological findings were validated through patient samples and in vitro studies. RESULTS: Metformin amplified cell death, induced DNA fragmentation, decreased cell migration, and elevated ROS levels in hypoxic, radiated cells. Proteomic analyses revealed that GAPDH and TAGLN2 were identified as pivotal targets linked to the radiosensitizing effect of metformin. Oral cancer patients exhibited elevated levels of TAGLN2 and reduced levels of GAPDH. Metformin downregulated TAGLN2 and upregulated GAPDH in hypoxic, radiated cells. Additionally, metformin reduced levels of mutated p53. CONCLUSIONS: This study suggests that metformin can enhance radiosensitivity in hypoxic cells, operating through modulation of GAPDH and TAGLN2. Furthermore, metformin effectively reduces mutated p53 levels in radiated cells under hypoxic conditions.

Coadministration of sitagliptin or metformin has no major impact on the adverse metabolic outcomes induced by dexamethasone treatment in rats.

AIMS: Glucocorticoids (GC) in excess cause glucose intolerance and dyslipidemia due to their diabetogenic actions. Conceptually, antidiabetic drugs should attenuate these side effects. Thus, we evaluated whether the coadministration of metformin or sitagliptin (or both) with dexamethasone could attenuate GC-induced adverse effects on metabolism. MATERIALS AND METHODS: Adult male rats were treated for 5 consecutive days with dexamethasone (1 mg/kg, body mass (bm), intraperitoneally). Additional groups were coadministered with metformin (300 mg/kg, bm, by oral gavage (og)) or sitagliptin (20 mg/kg, bm, og) or with both compounds in combination. The day after the last treatments, rats were submitted to glucose tolerance tests, pyruvate tolerance test, and euthanized for biometric, biochemical, morphologic, and molecular analyses. KEY FINDINGS: Dexamethasone treatment resulted in reduced body mass and food intake, increased blood glucose and plasma insulin, dyslipidemia, glucose intolerance, pyruvate intolerance, and increased hepatic content of glycogen and fat. Sitagliptin coadministration improved glucose tolerance compared with the control group, an effect paralleled with higher levels of active GLP-1 during an oral GTT. Overall, sitagliptin or metformin coadministration did not prevent any of the dexamethasone-induced metabolic disturbances. SIGNIFICANCE: Coadministration of sitagliptin or metformin result in no major improvement of glucose and lipid metabolism altered by dexamethasone treatment in male adult rats.

Evaluación de la prescripción de hipoglucemiantes orales en población adulta con Diabetes Mellitus Tipo 2 / Evaluation of the prescription of oral hypoglycemic agents in the adult population with type 2 diabetes mellitus

En el nivel primario de atención se detectan errores en la prescripción del tratamiento farmacológico de la diabetes tipo 2. El objetivo de este estudio fue evaluar la calidad de la prescripción de hipoglucemiantes orales en pacientes atendidos en consultorios del médico de la familia del Policlínico Universitario Hermanos Cruz, municipio Pinar del Río, Cuba. Se realizó un estudio de utilización de medicamentos de tipo descriptivo y transversal clasificado dentro de estos como de indicación-prescripción con elementos de esquema terapéutico y de factores que condicionan los hábitos de prescripción. El universo estuvo conformado por 1575 pacientes con diagnóstico de diabetes mellitus tipo 2 tratados con hipoglucemiantes orales que pertenecían a los 20 consultorios médicos de la familia.La muestra de estudio se obtuvo por el método de muestreo no probabilístico (por conveniencia) (n=846). La información se obtuvo de la historia clínica y tarjeta control de los pacientes para adquirir estos medicamentos. Predominó la edad de 40-49 años, el sexo femenino y entre 5-10 años de evolución de la enfermedad. No se usó la primera línea de tratamiento en el 43,6 % de los casos, ningún caso tenía estudios de laboratorio para el uso de la Metformina. La prescripción y dosis fue adecuada no así su uso racional. Las interacciones más frecuentes fueron las farmacocinéticas.El uso racional de hipoglucemiantes orales fue deficiente lo que hace necesario ampliar la divulgación de un protocolo de tratamiento para mejorar el uso de estos fármacos en el nivel primario de atención.

Errors in the prescription of drug treatment for type 2 diabetes are detected at the primary level of care. the purpose of this study was to evaluate the quality of the prescription of oral hypoglycemic agents in patients attended in the family doctor's offices of the Hermanos Cruz University Polyclinic, Pinar del Río distrit, Cuba. A descriptive and cross-sectional study of the use of medications was carried out, classified within these as indication-prescription with elements of the therapeutic scheme and factors that condition prescription habits. The universe was made up of 1575 patients diagnosed with type 2 diabetes mellitus treated with oral hypoglycemic agents who belonged to the 20 family medical offices. The study sample was carried out by the non-probabilistic sampling method (for convenience) (n = 846). The information was obtained from the clinical history and control card of the patients to acquire these medications. The age of 40-49 years, the female sex and between 5-10 years of evolution of the disease predominated. The first line of treatment was not used in 43.6% of the cases; no case had laboratory studies for the use of Metformin. The prescription and dose was adequate, but not its rational use. The most frequent interactions were pharmacokinetic ones.The rational use of oral hypoglycemic agents was deficient, which makes it necessary to expand the dissemination of a treatment protocol to improve the use of these drugs at the primary level of care.

The Use of Oral Hypoglycemic Agents during Pregnancy: An Alternative to Insulin?

OBJECTIVE: Gestational Diabetes Mellitus (GDM) and Type 2 Diabetes Mellitus (DM2) are metabolic disorders characterized by increased insulin resistance. Although insulin is the treatment of choice in pregnant patients with DM, the prescription of oral hypoglycemic agents (OHA) has been increasing among practitioners. This study aimed to evaluate the maternal and neonatal outcomes when oral hypoglycemic agents were used in diabetic pregnant women. METHODS: Medical records from the Maternal-Infant Care Unit Clinics SoM-UPR (n=149) were reviewed. Patients that were treated with metformin, sulfonylurea or insulin were included. Maternal and neonatal outcomes were compared between groups. RESULTS: Patient's mean age was 28 ± 6 years. The majority had GDM (91%). The most common comorbidity was hypertension (9.9%). Lifestyle modification was used as treatment in 77% of patients during the second trimester, but its use decreased to 33% during the third trimester. Insulin was the treatment of choice. Among the OHA, sulfonylurea was preferred. Postprandial glucose levels were lower in patients who used insulin as compared to those without medications. CONCLUSION: No significant differences were found in maternal outcomes such as C-section, induction of labor, episiotomy or preterm labor, or neonatal outcomes such as macrosomia, neonatal hypoglycemia or congenital abnormalities among treatment groups. OHA can be considered as an alternative to insulin for the treatment of DM during pregnancy in selected cases.

Tratamento para o diabetes mellitus gestacional: uma revisão de literatura / Treatment for gestational diabetes mellitus: a literature review

O diabetes mellitus gestacional (DMG) é uma complicação que atinge o metabolismo da gestante, resultando em intolerância à glicose e consequente hiperglicemia, originada pela insuficiência de insulina materna. Este estudo tem como objetivo identificar os tratamentos disponíveis e mais utilizados para o DMG. Trata-se de um uma revisão de literatura, feita a partir de 22 referências, acerca dos tratamentos para o DMG. As bases de dados escolhidas foram Google Acadêmico, UpToDate, SciELO e o acervo da Universidade do Planalto Catarinense. Estudos apontam a insulina humana ­ NPH e regular ­ como a principal escolha, quando comparada aos seus análogos, apesar de ainda existirem muitas controvérsias quanto ao início do tratamento, o esquema terapêutico e os ajustes das doses. Pesquisas têm demonstrado bons resultados sobre a eficácia e a segurança dos hipoglicemiantes orais ­ gliburida e metformina ­ no tratamento de gestantes diabéticas, mas é evidente a necessidade de mais estudos para confirmar a efetividade deles e garantir um bom desenvolvimento do concepto. Concluiu-se que o controle dietético e o exercício físico são a primeira opção de tratamento para o DMG. Todavia, caso a euglicemia não seja atingida, opta-se pelo tratamento medicamentoso por meio da insulinoterapia ou hipoglicemiantes orais, o que possibilita a redução da incidência dos efeitos adversos ao binômio materno-fetal.(AU)

Gestational diabetes mellitus (DMG) is a complication that affects the pregnant woman's metabolism, resulting in glucose intolerance and consequent hyperglycemia, caused by insufficient maternal insulin. This study aims to identify the available and most used treatments for DMG. This is a literature review, based on 22 references, about treatments for Gestational Diabetes; the databases chosen were Google Scholar, UpToDate, SciELO and the collection of the Universidade do Planalto Catarinense. Studies point to human insulin ­ NPH and regular ­ as the main choice when compared to its analogues, although there are still many controversies about the beginning of treatment, therapeutic scheme and dose adjustments. Researches have shown good results on the efficacy and safety of oral hypoglycemic agents ­ glyburide and metformin ­ in the treatment of diabetic pregnant women, but it is evident the need for further studies to confirm their effectiveness and to guarantee a good development of the fetus. It was concluded that dietary control and physical exercise are the first treatment option for DGM. However, if euglycemia is not achieved, drug treatment is chosen through insulin therapy or oral hypoglycemic agents, which makes it possible to reduce the incidence of adverse effects to the maternal-fetal binomial.(AU)

Pharmacogenetic Evaluation of Metformin and Sulphonylurea Response in Mexican Mestizos with Type 2 Diabetes.

BACKGROUND: In Mexico, approximately 25% of patients with type 2 diabetes (T2D) have adequate glycemic control. Polymorphisms in pharmacogenetic genes have been shown to have clinical consequences resulting in drug toxicity or therapeutic inefficacy. OBJECTIVE: The study aimed to evaluate the impact of variants in genes known to be involved in response to oral hypoglycemic drugs, such as CYP2C9, OCT, MATE, ABCA1 and C11orf65, in the Mexican Mestizo population of T2D patients. METHODS: In this study, 265 patients with T2D were enrolled from the Hospital Juárez de México, Mexico City. Genotyping was performed by TaqMan® assays. SNP-SNP interactions were analyzed using the multifactor dimensionality reduction (MDR) method. RESULTS: Carriers of the del allele of rs72552763 could achieve better glycemic control than noncarriers. There was a significant difference in plasma glucose and HbA1c levels among rs622342 genotypes. The results suggested an SNP-SNP interaction between rs72552763 and rs622342 OCT1 and rs12943590 MATE2. CONCLUSION: The interaction between rs72552763 and rs622342 in OCT1, and rs12943590 in MATE2 suggested an important role of these polymorphisms in metformin response in T2D Mexican Mestizo population.

Exposição crônica ao cloridrato de metformina e à glibenclamida causa alterações comportamentais, glicêmicas e de mortalidade em Hemigrammus caudovittatus e Danio rerio / Chronic exposure to metformin chloridrate and glibenclamide causes behavioral, blood glucose and mortality changes of Hemigrammus caudovittatus and Danio rerio

Hemigrammus caudovittatus e Danio rerio foram expostos aos hipoglicemiantes orais (HOs) cloridrato de metformina a 40µg/L e 120µg/L e glibenclamida a 0,13µg/L e 0,39µg/L durante 100 dias. Foram avaliados os efeitos tóxicos dos fármacos em relação ao peso, ao comportamento animal, à glicemia e à mortalidade. H. caudovittatus expostos à menor concentração dos fármacos apresentaram aumento significativo (P<0,05) no evento Respiração Aérea. Ainda, foi observado aumento no comportamento Descansar quando os animais foram expostos à glibenclamida a 0,39µg/L. Em D. rerio expostos ao cloridrato de metformina a 120µg/L, foi observado aumento (P<0,05) no comportamento Descansar. A glibenclamida provocou redução (P<0,05) na glicemia de H. caudovittatus. Ambos os fármacos causaram efeito letal na espécie D. rerio, contudo a glibenclamida foi mais tóxica, causando 100% de mortalidade em 30 dias de exposição. Os animais que vieram a óbito apresentaram congestão nos arcos branquiais e hemorragia. Os HOs foram desenvolvidos para apresentarem efeitos fisiológicos em mamíferos, entretanto efeitos tóxicos foram encontrados nas duas espécies de peixe estudadas. Isso levanta a preocupação sobre possíveis efeitos tóxicos de HOs e sobre quais métodos serão utilizados para a sua degradação no ambiente aquático.(AU)

Hemigrammus caudovittatus and Danio rerio were exposed to oral hypoglycemic drugs (HOs) metformin hydrochloride at 40µg/L and 120µg/L and to glibenclamide at 0.13µg/L and 0.39µg/L during 100 days. Toxic effects of the drugs were evaluated based on weight, animal behavior, blood glucose and mortality. H. caudovittatus exposed to lowest concentration of the drugs showed significant increase (P< 0.05) in the Air breathing event. Furthermore, increase in Rest event was observed when animals were exposed to glibenclamide at 0.39µg/L. An increase (P< 0.05) in the frequency of Rest behavior in the D. rerio exposed to metformin hydrochloride at 120µg/L was observed. Glibenclamide caused decrease (P< 0.05) in the blood glucose of H. caudovittatus. Both drugs caused lethal effect against D. rerio. Nevertheless, glibenclamide was more toxic causing 100% of mortality after 30 days of exposure. The animals that died showed congestion on the branchial arches and hemorrhage. The HOs were developed to have physiological effects in mammals. However, toxic effects were found in both species of fish studied. This raises concerns about possible toxic effects of HOs and what methods will be used for their degradation in the aquatic environment.(AU)

Exposição crônica ao cloridrato de metformina e à glibenclamida causa alterações comportamentais, glicêmicas e de mortalidade em Hemigrammus caudovittatus e Danio rerio / Chronic exposure to metformin chloridrate and glibenclamide causes behavioral, blood glucose and mortality changes of Hemigrammus caudovittatus and Danio rerio

Hemigrammus caudovittatus e Danio rerio foram expostos aos hipoglicemiantes orais (HOs) cloridrato de metformina a 40µg/L e 120µg/L e glibenclamida a 0,13µg/L e 0,39µg/L durante 100 dias. Foram avaliados os efeitos tóxicos dos fármacos em relação ao peso, ao comportamento animal, à glicemia e à mortalidade. H. caudovittatus expostos à menor concentração dos fármacos apresentaram aumento significativo (P<0,05) no evento Respiração Aérea. Ainda, foi observado aumento no comportamento Descansar quando os animais foram expostos à glibenclamida a 0,39µg/L. Em D. rerio expostos ao cloridrato de metformina a 120µg/L, foi observado aumento (P<0,05) no comportamento Descansar. A glibenclamida provocou redução (P<0,05) na glicemia de H. caudovittatus. Ambos os fármacos causaram efeito letal na espécie D. rerio, contudo a glibenclamida foi mais tóxica, causando 100% de mortalidade em 30 dias de exposição. Os animais que vieram a óbito apresentaram congestão nos arcos branquiais e hemorragia. Os HOs foram desenvolvidos para apresentarem efeitos fisiológicos em mamíferos, entretanto efeitos tóxicos foram encontrados nas duas espécies de peixe estudadas. Isso levanta a preocupação sobre possíveis efeitos tóxicos de HOs e sobre quais métodos serão utilizados para a sua degradação no ambiente aquático.(AU)

Hemigrammus caudovittatus and Danio rerio were exposed to oral hypoglycemic drugs (HOs) metformin hydrochloride at 40µg/L and 120µg/L and to glibenclamide at 0.13µg/L and 0.39µg/L during 100 days. Toxic effects of the drugs were evaluated based on weight, animal behavior, blood glucose and mortality. H. caudovittatus exposed to lowest concentration of the drugs showed significant increase (P< 0.05) in the Air breathing event. Furthermore, increase in Rest event was observed when animals were exposed to glibenclamide at 0.39µg/L. An increase (P< 0.05) in the frequency of Rest behavior in the D. rerio exposed to metformin hydrochloride at 120µg/L was observed. Glibenclamide caused decrease (P< 0.05) in the blood glucose of H. caudovittatus. Both drugs caused lethal effect against D. rerio. Nevertheless, glibenclamide was more toxic causing 100% of mortality after 30 days of exposure. The animals that died showed congestion on the branchial arches and hemorrhage. The HOs were developed to have physiological effects in mammals. However, toxic effects were found in both species of fish studied. This raises concerns about possible toxic effects of HOs and what methods will be used for their degradation in the aquatic environment.(AU)

Caracterización oftalmológica de diabéticos tipo II con catarata senil bilateral / Ophthalmological characterization of type 2 diabetics with bilateral senile cataract

Objetivo: Determinar las características oculares de los diabéticos tipo II con catarata senil bilateral. Métodos: Se realizó un estudio descriptivo transversal a 248 diabéticos tipo II con catarata senil bilateral, en el Instituto Cubano de Oftalmología Ramón Pando Ferrer, desde septiembre del año 2015 a septiembre de 2016. Resultados: Predominó el sexo femenino (69,6 Ophthalmological characterization of type 2 diabetics with bilateral senile cataract), la edad de 70,6 años, el índice de masa corporal en pacientes con sobrepeso (46,5 por ciento), el tiempo de evolución de 5-9 años (52,2 por ciento), el tratamiento con hipoglucemiantes orales (95,2 por ciento), la mejor agudeza visual sin corrección con daño retinal 0,1 y sin daño 0,3; y corregida sin daño 0,5 y con daño retinal 0,2, todas con la cartilla de Snellen; promedio de densidad celular endotelial de 2 143,15 ± 326,08 cel/mm2, un coeficiente de variabilidad de 53,18 ± 7,14 por cientoy una hexagonalidad de 42,68 ± 18,70 por ciento. Conclusiones: La asociación de diabetes mellitus tipo 2 y catarata senil bilateral es más frecuente en mujeres mayores de 70 años, sobrepeso u obesa con un tiempo de evolución de la diabetes mellitus de 5 a 9 años y controladas con hipoglucemiantes orales. La peor agudeza visual está relacionada con el daño en la retina; sin embargo, presentan queratometrías, biometrías y tensión ocular normal. No hay alteraciones en la densidad endotelial, pero sí pleomorfismo y polimegatismo(AU)

ABSTRACT Objective: Determine the ocular characteristics of type 2 diabetics with bilateral senile cataract. Methods: A descriptive cross-sectional study was conducted of 248 type 2 diabetics with bilateral senile cataract at Ramón Pando Ferrer Cuban Institute of Ophthalmology from September 2015 to September 2016. Results: A predominance of the female sex (69.6 percent), mean age 70.6 years, body mass index in overweight patients 46.5 percent, time of evolution 5-9 years (52.2 percent), treatment with oral hypoglycemic agents 95.2 percent, best visual acuity without correction with retinal damage 0.1 and without damage 0.3; best corrected visual acuity without retinal damage 0.5 and with damage 0.2, all according to the Snellen chart; average endothelial cell density 2 143.15 ± 326.08 cell/mm2, coefficient of variability 53.18 ± 7.14 percent and hexagonality 42.68 ± 18.70 percent. Conclusions: Coexistence of type 2 diabetes mellitus and bilateral senile cataract is more common among women aged over 70 years, overweight or obese, with a time of evolution of diabetes mellitus of 5 to 9 years, and controlled with oral hypoglycemic agents. The worst visual acuity is related to retinal damage. However, keratometries, biometries and ocular tension results were all normal. There were no endothelial density alterations, but there was pleomorfism and polymegethism(AU)

Sobrevida de los islotes β pancreáticos y uso de hipoglucemiantes orales: un gran reto para el médico actual / Survival of pancreatic islet β and use of oral hypoglycemic agents: a challenge for the current doctor

La célula β no sólo es capaz de fabricar y secretar la insulina, sino además, hace que dicha secreción sea en el momento justo y en la cantidad adecuada. Las elevaciones postprandiales de glucosa generan una respuesta secretora aguda en la célula β, pero en ciertas patologías como la diabética, el escenario cambia radicalmente, resultando en una disfunción caracterizada por un proceso secretor alterado y múltiples cambios fenotípicos. En estos, los nutrientes, glucosa y ácidos grasos, están elevados de forma crónica, convirtiéndose en sustancias tóxicas que pueden llevar a la muerte de la propia célula β. Por lo tanto, cualquier aproximación terapéutica a la cura de esta enfermedad debe afrontar la necesidad de reemplazar o evitar esta disminución celular, siendo imperativo mencionar el papel de los hipoglucemiantes orales como los inhibidores de la DPP-4 y los análogos de la GLP-1 en la protección contra el fracaso de la masa de células β.

The beta cell is not only able to produce and secrete insulin, but also makes this secretion is at the right time and in the right amount. Postprandial glucose elevations produce an acute secretory response in the beta cell, but in certain diseases such as diabetes mellitus, the scene changes dramatically, resulting in dysfunction, characterized by an altered secretion process and multiple phenotypic changes. In these, nutrients like glucose and fatty acids are chronically elevated, becoming toxic substances that can lead to death of the beta cell itself. Therefore, any therapeutic approach to cure this disease must face the need to replace or avoid this cell decline, it is imperative to mention the role of oral hypoglycemic agents as inhibitors of DPP-4 and analogs of the GLP-1 in protection against failure of the β cell mass.

Uptake of new antidiabetic medications in three emerging markets: a comparison between Brazil, China and Thailand.

OBJECTIVES: New antidiabetic medications such as insulin analogues and thiazolidinediones have been introduced over the last decade. This study compares the uptake of new agents in three emerging pharmaceutical markets: Brazil, China, and Thailand. METHODS: Using longitudinal IMS Health sales data, we calculated the quarterly percentage market share for types of insulins and oral hypoglycemic agents from 2002 through 2012 in each country. New oral hypoglycemic agents included: alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and non-sulfonylurea secretagogues. RESULTS: While China had the highest use of insulin cartridges and pens (85.6% in 2010), Brazil was the earliest adopter of insulin analogues and had the greatest use of these products overall (44.6% of the insulin market) in 2010, which then decreased by almost half by 2012. Together, sulfonylureas and metformin dominated the markets in Brazil and Thailand (~89% and ~96% respectively) over the 10-year period. Between 2002 and 2012, there was a shift in use from sulfonylureas to metformin; the market share of newer agents remained 10% or less in both countries. In China, however, market share of new oral agents grew rapidly from 13.1% to 44.4%. While metformin use was relatively stable in China (one-third of the market), sulfonylureas declined substantially over the 10-year period (41.5% to 20.8%). CONCLUSION: Given large cost differentials between newer and older insulins and among oral hypoglycemic agents, it is important to evaluate uptake of newer products over time. Uptake patterns differed in the study countries, likely due to different medicines policy approaches. Future research should evaluate how trends in use of antidiabetic products align with national clinical practice guidelines and pharmaceutical policies, as well as the impacts of different patterns of use on cost and clinical outcomes.

Uso de hipoglicemiantes orales durante la lactancia / Use of oral hypoglycemic agents during breastfeeding

Antecedentes: Los hipoglicemiantes orales son una alternativa emergente en el tratamiento de la diabetes mellitus gestacional (DMG), pero existe poca información acerca de su uso durante la lactancia. Objetivo: Revisar la evidencia respecto a la seguridad del uso de los hipoglicemiantes orales durante la lactancia. Resultados: Encontramos 3 trabajos que evaluaron el paso de metformina a la leche materna: hubo traspaso de metformina a leche materna en todos los casos. La concentración de metformina excretada a la leche fue en promedio 48 por ciento de la concentración plasmática materna. Las dosis calculadas que recibieron los lactantes en promedio fue 0,38 por ciento de la dosis materna, ajustada por peso. La concentración promedio de metformina en los lactantes fue de 0,025 mg/L. No se reportaron efectos adversos en los lactantes, incluso en el seguimiento a 6 meses de vida. Se encontró sólo un trabajo en relación a glibenclamida y lactancia materna, en el que no se detectó excreción del fármaco a la leche materna. Conclusiones: Los hipoglicemiantes orales parecen ser medicamentos seguros durante la lactancia, sin embargo, la evidencia es escasa. Sugerimos el uso de la glibenclamida por sobre metformina, por su nulo paso a la leche materna.

Background: Oral hypoglycemic agents are an emergent therapy for the treatment of gestational diabetes mellitus (GDM), but there is little information about its use during breastfeeding. Objectives: To review the available evidence regarding the use and safety of oral hypoglycemic agents during breastfeeding. Results: We found 3 studies that described the transfer of metformin to breast milk; there was transfer of metformin to breast milk in all cases. The concentration of metformin in breast milk was 48 percent of the maternal plasma concentration. The calculated dose for the infants was 0.38 percent of the maternal weight adjusted dose. The mean concentration of metformin in the infant's plasma was 0.025 mg/L. No adverse effects were reported in the infants, including 6 months of follow-up. Only one study investigated glyburide and breastfeeding, showing no excretion to breast milk. Conclusion: Oral hypoglycemic agents seem to be safe during breastfeeding; however, the available data is scarce. We suggest the use of glyburide over metformin because of its null excretion to breast milk.

Hipoglicemiantes orales para el tratamiento de la diabetes mellitus gestacional: revisión sistemática de la literatura / Oral hypoglycaemic agents for the treatment of gestational diabetes mellitus: systematic review of the literature

Antecedentes: la diabetes mellitus gestacional (DMG) se asocia a mayor riesgo materno y perinatal. El manejo habitual de ésta patología es la dieta, el ejercicio y la insulina. Los hipoglicemiantes orales (HGO) son una terapia emergente para el tratamiento de la DMG. Objetivos: realizar una revisión sistemática de toda la evidencia tipo I disponible acerca del uso de HGO para tratamiento de DMG y realizar un metaanálisis de los resultados maternos y perinatales significativos. Resultados: diez estudios cumplieron criterios de selección. Tres estudios comparaban metformina vs insulina, cuatro gliburide vs insulina y tres metformina vs gliburide. Los estudios no encontraron diferencias significativas en control glicémico ni en complicaciones perinatales entre metformina vs insulina, gliburide vs insulina y metformina vs gliburide. Nuestro metaanálisis mostró que la glicemia de ayuno es significativamente menor (DM 1,74; IC95 por ciento 0,383,10) y la glicemia postprandial a las 2 horas es significativamente mayor en el grupo insulina vs HGO (DM -2,97; IC95 por ciento -27,24 a -5,36). Nuestro metaanálisis muestra que la incidencia de fetos grandes para edad gestacional fue significativamente menor en el grupo metformina vs gliburide (OR 0,38; IC95 por ciento 0,18-0,78). El fracaso del tratamiento con gliburide fue significativamente menor que con metformina (27,6 por ciento vs 38,5 por ciento, p<0,0001; IC95 por ciento 1,21-1,60). Conclusión: los HGO son un tratamiento seguro y efectivo para DMG. Recomendamos gliburide (glibenclamida) para el tratamiento de las pacientes con DMG que fracasan su control glicémico con dieta y ejercicio, por no cruzar la placenta, tener menor tasa de fallo y ser igualmente efectiva que metformina.

Background: gestational diabetes mellitus (GDM) is associated to a higher maternal and perinatal risk. Usually GDM is controlled with diet, exercise and insulin. Oral hypoglycaemic agents (OHA) are an emergent therapy for the treatment of GDM. Objectives: conduct a systematic review of all class I evidence available regarding the use of OHA for GDM treatment, and perform a metaanalysis of significant maternal and perinatal outcomes. Results: ten studies accomplished inclusion criteria. Three studies compared metformin to insulin, four compared glyburide to insulin and three compared metformin to glyburide. Studies showed no significant differences in glycaemic control or perinatal complications, between metformin and insulin, between glyburide and insulin, or between metformin and glyburide. Our metaanalysis comparing OHA to insulin shows significantly lower fasting blood glucose (MD 1.74; 95 percent IC 0.38-3.10) and larger 2-hr postprandial glucose in the insulin group compared to OHA groups (MD -2.97; 95 percent IC -27.24-5.36). Our metaanalysis comparing shows a significantly lower incidence of large for gestational age in the metformin vs. gliburide group (OR 0.38; 95 percent IC 0.18-0.78). Failure of treatment was significantly lower using gliburide than metformin (27.6 percent vs. 38.5 percent, p<0.0001; 95 percent IC 1.21-1.60). Conclusion: OHA are a safe and effective treatment for GDM. We recommend the use of glyburide (glibenclamide) in GDM patients that fail to obtain glycemic control with diet and exercise, since glyburide does not crosses the placental barrier, has a lower rate of treatment failure and is equally affective as metformin.