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Pronunciation
(met FOR min)
Generic Available (U.S.)
Yes: Excludes solution
Index Terms
Metformin Hydrochloride
Brand Names: U.S.
Fortamet
Glucophage
Glucophage XR
Glumetza
Riomet
Brand Names: Canada Apo-Metformin
Ava-Metformin
CO Metformin
Dom-Metformin
Glucophage
Glumetza
Glycon
JAMP-Metformin
JAMP-Metformin Blackberry Med-Metformin
Mylan-Metformin
Novo-Metformin
Nu-Metformin
PHL-Metformin
PMS-Metformin
PRO-Metformin
Q-Metformin
RAN-Metformin
ratio-Metformin
Riva-Metformin
Sandoz-Metformin FC
Pharmacologic Category
Antidiabetic Agent, Biguanide
Pharmacologic Category Synonyms
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Biguanide
Oral Hypoglycemic Agent, Biguanide
Use: Labeled Indications
Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM) when hyperglycemia
cannot be managed with diet and exercise alone.
Use: Unlabeled
Gestational diabetes mellitus (GDM); polycystic ovary syndrome (PCOS); prevention of type 2
diabetes mellitus
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events have not been observed in animal studies; therefore, metformin is classified as
pregnancy category B. Metformin has been found to cross the placenta in concentrations which
may be comparable to those found in the maternal plasma. Pharmacokinetic studies suggest that
clearance of metformin may be increased during pregnancy and dosing may need adjusted in some
women when used during the third trimester.Fetal, neonatal, and maternal outcomes have been
evaluated following maternal use of metformin for the treatment of GDM and type 2 diabetes.
Available information suggests that metformin use during pregnancy may be safe as long as good
glycemic control is maintained; however, many studies used metformin during the second or third
trimester only. Maternal hyperglycemia can be associated with adverse effects in the fetus,
including macrosomia, neonatal hyperglycemia, and hyperbilirubinemia; the risk of congenitalmalformations is increased when the Hb A1c is above the normal range. Diabetes can also be
associated with adverse effects in the mother. Poorly-treated diabetes may cause end-organ
damage that may negatively affect obstetric outcomes. Physiologic glucose levels should be
maintained prior to and during pregnancy to decrease the risk of adverse events in the mother and
the fetus. Until additional safety and efficacy data are obtained, the use of oral agents is generally
not recommended as routine management of GDM or type 2 diabetes mellitus during pregnancy.
Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.Metformin has also
been evaluated for the treatment of PCOS, a syndrome which may exhibit oligomenorrhea and, in
some women, hyperinsulinemia. It is not recommended as first-line therapy; when used to treatinfertility related to PCOS, current guidelines restrict the use of metformin to women with glucose
intolerance. Because ovulation rates will likely improve in women with PCOS who are taking
metformin, appropriate contraceptive measures should be discussed in women who are not
attempting to conceive.
Lactation
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Enters breast milk/not recommended
Breast-Feeding Considerations
Low amounts of metformin (generally 1% of the weight-adjusted maternal dose) are excreted into
breast milk. Breast-feeding is not recommended by the manufacturer. Because breast milk
concentrations of metformin stay relatively constant, avoiding nursing around peak plasma
concentrations in the mother would not be helpful in reducing metformin exposure to the infant.
Growth and development were not affected in infants born to mothers with PCOS and who took
metformin while breast-feeding.
Contraindications
Hypersensitivity to metformin or any component of the formulation; renal disease or renal
dysfunction (serum creatinine 1.5 mg/dL in males or 1.4 mg/dL in females) or abnormal creatinine
clearance from any cause, including shock, acute myocardial infarction, or septicemia; acute or
chronic metabolic acidosis with or without coma (including diabetic ketoacidosis)
Note: Temporarily discontinue in patients undergoing radiologic studies in which intravascular
iodinated contrast media are utilized.
Warnings/Precautions
Boxed warnings:
Lactic acidosis: See Concerns related to adverse effects below.
Concerns related to adverse effects:
Cardiovascular mortality: Administration of oral antidiabetic drugs has been reported to be
associated with increased cardiovascular mortality; metformin does not appear to share this risk.
Lactic acidosis:[U.S. Boxed Warning]: Lactic acidosis is a rare, but potentially severe
consequence of therapy with metformin. Lactic acidosis should be suspected in any patient with
diabetes receiving metformin with evidence of acidosis but without evidence of ketoacidosis.
Discontinue metformin in clinical situations predisposing to hypoxemia, including conditions such as
cardiovascular collapse, respiratory failure, acute myocardial infarction, acute congestive heart
failure, and septicemia. The risk of accumulation and lactic acidosis increases with the degree of
impairment of renal function.
Disease-related concerns:
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Heart failure: Use caution in patients with congestive heart failure requiring pharmacologic
management, particularly in patients with unstable or acute heart failure; risk of lactic acidosis may
be increased secondary to hypoperfusion.
Hepatic impairment: Avoid use in patients with impaired liver function due to potential for lactic
acidosis.
Renal impairment: Metformin is substantially excreted by the kidney; patients with renal function
below the limit of normal for their age should not receive therapy. Use of concomitant medications
that may affect renal function (ie, affect tubular secretion) may also affect metformin disposition.
Metformin should be withheld in patients with dehydration and/or prerenal azotemia.
Stress-related states: It may be necessary to discontinue metformin and administer insulin if the
patient is exposed to stress (fever, trauma, infection, surgery).
Special populations:
Elderly: Metformin should not be initiatedin patients 80 years of age unless normal renal function
is confirmed.
Dosage form specific issues:
Extended release tablet: Insoluble tablet shell (Glumetza 1000 mg tablet) may remain intact and
be visible in the stool. Other extended released tablets (Fortamet, Glucophage XR, Glumetza
500 mg) may appear in the stool as a soft mass resembling the tablet.
Other warnings/precautions:
Ethanol use: Instruct patients to avoid excessive acute or chronic ethanol use; ethanol may
potentiate metformin's effect on lactate metabolism.
Iodinated contrast: Therapy should be temporarily discontinued prior to or at the time of
intravascular administration of iodinated contrast media (potential for acute alteration in renal
function). Metformin should be withheld for 48 hours after the radiologic study and restarted only
after renal function has been confirmed as normal.
Surgical procedures: Therapy should be suspended for any surgical procedures (resume only
after normal oral intake resumed and normal renal function is verified).
Adverse Reactions
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>10%:
Gastrointestinal: Diarrhea (IR tablet: 12% to 53%; ER tablet: 10% to 17%), nausea/vomiting (IR
tablet: 7% to 26%; ER tablet: 7% to 9%), flatulence (12%)
Neuromuscular & skeletal: Weakness (9%)
1% to 10%:
Cardiovascular: Chest discomfort, flushing, palpitation
Central nervous system: Headache (6%), chills, dizziness, lightheadedness
Dermatologic: Rash
Endocrine & metabolic: Hypoglycemia
Gastrointestinal: Indigestion (7%), abdominal discomfort (6%), abdominal distention, abnormal
stools, constipation, dyspepsia/ heartburn, taste disorder
Neuromuscular & skeletal: Myalgia
Respiratory: Dyspnea, upper respiratory tract infection
Miscellaneous: Diaphoresis increased, vitamin B12 levels decreased (7%), flu-like syndrome, nail
disorder
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Cimetidine: May increase the serum concentration of MetFORMIN. Risk D: Consider therapy
modification
Corticosteroids (Orally Inhaled): May diminish the hypoglycemic effect of Antidiabetic Agents. In
some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute
adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin
or other antidiabetic agent use. Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the hypoglycemic effect of Antidiabetic Agents. In some
instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal
crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other
antidiabetic agent use. Risk C: Monitor therapy
Dalfampridine: May increase the serum concentration of MetFORMIN. MetFORMIN may increase
the serum concentration of Dalfampridine. Risk C: Monitor therapy
Dofetilide: MetFORMIN may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Glycopyrrolate: May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy
Iodinated Contrast Agents: May enhance the adverse/toxic effect of MetFORMIN. Renal dysfunction
that may be caused by iodinated contrast agents may lead to metformin-associated lactic acidosis.
Management: Withhold metformin from all patients receiving intravascular iodinated contrast agents
prior to or at the time of the procedure and for at least 48 hrs thereafter. Document adequate renalfunction before restarting metformin. Risk D: Consider therapy modification
LamoTRIgine: May increase the serum concentration of MetFORMIN. Management: The
lamotrigine Canadian product monograph states that coadministration of these drugs is not
recommended. Risk C: Monitor therapy
Luteinizing Hormone-Releasing Hormone Analogs: May diminish the therapeutic effect of
Antidiabetic Agents. Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Somatropin: May diminish the hypoglycemic effect of Antidiabetic Agents. Risk D: Consider therapy
modification
Thiazide Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor
therapy
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Trospium: MetFORMIN may decrease the serum concentration of Trospium. Risk C: Monitor
therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid or limit ethanol (incidence of lactic acidosis may be increased; may cause
hypoglycemia).
Food: Food decreases the extent and slightly delays the absorption. May decrease absorption of
vitamin B12 and/or folic acid.
Herb/Nutraceutical: Caution with chromium, garlic, gymnema (may cause hypoglycemia).
Storage
Oral solution: Store at 15C to 30C (59F to 86F).
Tablets: Store at 20C to 25C (68F to 77F); excursion permitted to 15C to 30C (59F to 86F).
Protect from light and moisture.
Mechanism of Action
Decreases hepatic glucose production, decreasing intestinal absorption of glucose and improves
insulin sensitivity (increases peripheral glucose uptake and utilization)
Pharmacodynamics/Kinetics
Onset of action: Within days; maximum effects up to 2 weeks
Distribution: Vd: 654 358 L; partitions into erythrocytes
Protein binding: Negligible
Metabolism: Not metabolized by the liver
Bioavailability: Absolute: Fasting: 50% to 60%
Half-life elimination: Plasma: 4-9 hours
Time to peak, serum: Immediate release: 2-3 hours; Extended release: 7 hours (range: 4-8 hours)
Excretion: Urine (90% as unchanged drug; active secretion)
Dosage
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Type 2 diabetes management: Note: Allow 1-2 weeks between dose titrations: Generally, clinically
significant responses are not seen at doses 2000 mg/day is required, it may
be better tolerated in three divided doses. Maximum recommended dose 2550 mg/day.
Extended release tablet: Oral: Note: If glycemic control is not achieved at maximum dose, may
divide dose and administer twice daily.
Children 17 years and Adults:
Fortamet: Initial: 500-1000 mg once daily; dosage may be increased by 500 mg weekly; maximum
dose: 2500 mg once daily
Glucophage XR: Initial: 500 mg once daily; dosage may be increased by 500 mg weekly;
maximum dose: 2000 mg once daily
Adults: Glumetza: Initial: 1000 mg once daily; dosage may be increased by 500 mg weekly;
maximum dose: 2000 mg once daily
Elderly: The initial and maintenance dosing should be conservative, due to the potential for
decreased renal function. Generally, elderly patients should not be titrated to the maximum dose of
metformin. Do not use in patients 80 years of age unless normal renal function has been
established.
Transfer from other antidiabetic agents: No transition period is generally necessary except when
transferring from chlorpropamide. When transferring from chlorpropamide, care should be exercised
during the first 2 weeks because of the prolonged retention of chlorpropamide in the body, leading
to overlapping drug effects and possible hypoglycemia.
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Concomitant metformin and oral sulfonylurea therapy: If patients have not responded to 4
weeks of the maximum dose of metformin monotherapy, consider a gradual addition of an oral
sulfonylurea, even if prior primary or secondary failure to a sulfonylurea has occurred. Continue
metformin at the maximum dose. If adequate response has not occurred following 3 months of
metformin and sulfonylurea combination therapy, consider switching to insulin with or withoutmetformin.
Failed sulfonylurea therapy: Patients with prior failure on glyburide may be treated by gradual
addition of metformin. Initiate with glyburide 20 mg and metformin 500 mg daily. Metformin dosage
may be increased by 500 mg/day at weekly intervals, up to a maximum metformin dose (dosage of
glyburide maintained at 20 mg/day).
Concomitant metformin and insulin therapy: Initial: 500 mg metformin once daily, continue
current insulin dose; increase by 500 mg metformin weekly until adequate glycemic control is
achieved
Maximum daily dose: Immediate release and solution: 2550 mg metformin; Extended release: 2000-
2500 mg (varies by product)
Decrease insulin dose 10% to 25% when FPG
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Monitoring Parameters
Urine for glucose and ketones, fasting blood glucose, hemoglobin A 1c, and fructosamine. Initial and
periodic monitoring of hematologic parameters (eg, hemoglobin/hematocrit and red blood cell
indices) and renal function should be performed, at least annually. While megaloblastic anemia has
been rarely seen with metformin, if suspected, check vitamin B12and folate if anemia is present.
Reference Range
Recommendations for glycemic control in nonpregnant adults with diabetes (ADA, 2012):
Hb A1c:
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mortality, hypoglycemia requiring assistance, and weight gain in adult type 2 diabetes. How "tightly"
to control a geriatric patient's blood glucose needs to be individualized. Such a decision should be
based on several factors, including the patient's functional and cognitive status, how well he/she
recognizes hypoglycemic or hyperglycemic symptoms, and how to respond to them and other
disease states. An Hb A1c
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Assess for signs and symptoms of vitamin B12 and/or folic acid deficiency during therapy;
supplementation may be required. Refer patient to diabetes educator for instruction if needed.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific
product labeling.
Solution, oral, as hydrochloride:
Riomet: 100 mg/mL (118 mL, 473 mL) [dye free, ethanol free, sugar free; contains saccharin;
cherry flavor]
Tablet, oral, as hydrochloride: 500 mg, 850 mg, 1000 mg
Glucophage: 500 mg, 850 mg
Glucophage: 1000 mg [scored]
Tablet, extended release, oral, as hydrochloride: 500 mg, 750 mg, 1000 mg
Fortamet: 500 mg, 1000 mg
Glucophage XR: 500 mg, 750 mg
Glumetza: 500 mg, 1000 mg
Pricing: U.S. (www.drugstore.com)
Solution (Riomet)
500 mg/5 mL (473): $201.59
Tablet, 24-hour(Fortamet)
500 mg (60): $338.55
1000 mg (60): $683.99
Tablet, 24-hour(Glucophage XR)
500 mg (60): $69.99
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750 mg (30): $53.99
Tablet, 24-hour(Glumetza)
500 mg (100): $389.00
1000 mg (100): $859.97
Tablet, 24-hour(MetFORMIN HCl)
500 mg (90): $20.99
750 mg (30): $32.99
Tablets (Glucophage)
500 mg (60): $69.99
850 mg (60): $113.29
1000 mg (60): $141.08
Tablets (MetFORMIN HCl)
500 mg (60): $12.99
850 mg (90): $77.99
1000 mg (30): $17.99
La epidemia de la diabetes mellitus (DM) es reconocida por la Organizacin Mundialde la Salud (OMS) como una amenaza mundial. En 2005 se registraron 1.1 millones demuertes debidas a la diabetes, de las cuales alrededor de 80% ocurrieron en pasesde ingresos bajos o medios, que en su mayora se encuentran menos preparadospara enfrentar esta epidemia.
De conformidad con la informacin de la Encuesta Nacional de Salud y Nutricin2006 (ENSANUT) la prevalencia aument a 14%, lo que representa un total de 8millones de personas con diabetes; en la poblacin urbana, la prevalencia fuesignificativamente mayor.
En Mxico, la DM ocupa el primer lugar en nmero de defunciones por ao, tanto enhombres como en mujeres las tasas de mortalidad muestran una tendencia
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ascendente en ambos sexos con ms de 70 mil muertes y 400,000 casos nuevosanuales cabe sealar que segn la Direccin General de Informacin en Salud en el2007 hubo un nmero mayor de defunciones en el grupo de las mujeres (37,202muertes) comparado con el de los hombres (33,310), con una tasa 69.2 por 100,000habitantes en mujeres y de 64 en hombres, diferencias importantes a considerar en lasacciones preventivas, de deteccin, diagnstico y tratamiento de este
padecimiento. La diabetes no es un factor de riesgo cardiovascular.
Es un equivalente de enfermedad cardiovascular debido a que el riesgo de sufrir undesenlace cardiovascular es igual al de la cardiopata isqumica.
FUENTE: NORMA Oficial Mexicana NOM-015-SSA2-2010, Para la prevencin,tratamiento y control de la diabetes mellitus.
La diabetes mellitus es un factor de riesgo cardiovascular, se estima que entre 7 y 8 decada 10 personas con diabetes mueren por problema macrovascular.
Fuente: Secretaria deGobernacin,http://www.dof.gob.mx/documentos/3868/Salud/Salud.htm
Encuesta Nacional de Salud y Nutricin 2006 (ENSANUT)
ESTADSTICAS DIABETES
Cada hora se diagnostican 38 nuevos casos de diabetes
Cada dos horas mueren 5 personas a causa de complicaciones originadas por ladiabetes
De cada 100 pacientes con diabetes, 14 presenta alguna complicacin renal
El 30% de los problemas de pie diabtico termina en amputacin
De cada cinco pacientes con diabetes, 2 desarrollan ceguera
Mxico ocupa el dcimo lugar en diabetes mundial y se estima que para 2030 ocupeel sptimo puesto.
Fuente: Presentacin: Impacto de la Diabetes Mellitus desde la perspectivainstitucional. Dr. Ernesto Alcntar Luna
Prevalencia de diabetes tipo 1 en nios
2010Poblacin total infantil (0-14 aos, miles demillones)
1.9
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ipo 1 en nios (0-14 aos)Nmero de nios con diabetes tipo 1 (miles) 479.6Nmero de casos de recin diagnostico por ao(miles)
75.8
Incremento anualincidencia(%) 3.0
IMSS Declar en octubre 2010: 400 mil nios diabetes tipo 1 y 2 son atendidospor esa institucin.
Datos sobre Diabetes en nios tipo 2
Hospital General: 600 pacientes menores de 18 aos Fuente: FederacinMexicana de Diabetes, A.C.
Hospital infantil: 150 pacientes. Fuente: Federacin Mexicana de Diabetes, A.C.
La diabetes tipo 1 se encuentra en rpido crecimiento en nios y adolescentes en
muchos pases, y las pruebas sugieren que hoy da se estn detectando casos dediabetes tipo 2 en nios en un nmero creciente de pases.Se calcula que, anualmente, alrededor de 76.000 nios de menos de 15 aosdesarrollan diabetes tipo 1 en el mundo. De los 480.000 nios que se calcula tienendiabetes tipo 1, el 24% procede de la regin del Sudeste Asitico, pero la reginEuropea se le aproxima estrechamente, ocupando el segundo lugar (23%).Fuente:http://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundial
*Obesidad y sobrepeso
Uno de cada tres adolescentes de entre 12 y 19 aos tiene obesidad u sobrepeso.Aproximadamente 5 millones 757mil 400 adolescentes
La prevalencia de sobrepeso fue ms alta en hombres mayores a 20 aos (42.5%) queen mujeres de ms de20 aos (37.4%), sin embargo la prevalencia de obesidad enmujeres fue de 34.5% y en hombres de 24.2%. Por la tanto, la prevalencia desobrepeso y obesidad a nivel nacional fue de 71.9% en mujeres mayores de 20 aos y66.7% en hombres mayores de 20 aos.
http://www.fmdiabetes.org/fmd/pag/diabetes_numeros.php
Distrito Federal
Prevalencia de diabetes en adultos de 20 aos o ms es de 8.9%, siendo ms
elevada en mujeres (9.1%) que en hombres (8.6%)
Factores de riesgo para enfermedades crnicas
http://archive.diabetesatlas.org/es/glossary/term/17http://archive.diabetesatlas.org/es/glossary/term/17http://archive.diabetesatlas.org/es/glossary/term/17http://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://www.fmdiabetes.org/fmd/pag/diabetes_numeros.phphttp://www.fmdiabetes.org/fmd/pag/diabetes_numeros.phphttp://www.fmdiabetes.org/fmd/pag/diabetes_numeros.phphttp://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://archive.diabetesatlas.org/es/glossary/term/177/28/2019 Biografia metformina
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Se estima que ms del 27% de los adultos de 20 aos o ms fumaban y casi
14% haba fumado alguna vez hasta el momento de realizarse la Encuesta de
Nacional de Salud y Nutricin 2006
17.3% de los adultos reportaron haber consumido ms de cinco copas en un
mismo da por lo menos una vez al mes
32.2% de los adolescentes de 12 a 19 aos present exceso de peso
La prevalencia de obesidad y sobrepeso en adultos de 20 aos o ms fue de
73%, 75.4% en mujeres y 69.8% en hombres
La diabetes mellitus afecta aproximadamente 24 millones de personas en EstadosUnidos. De stas, 17.9 millones han sido diagnosticadas, pero unos 6 millonesdesconocen que tienen la enfermedad.
Esta poblacin de personas con diabetes mellitus afecta a grupos tnicos:
Indoamericanos y nativos de Alaska (16.5 %)
Negros (11.8 %)
Hispanos (10.4 %)
Los hispanos registran las siguientes tasas:
Puertorriqueos (12.6 %)
Mxicoamericanos (11.9 %)
Cubanos (8.2 %)
Complicaciones
La diabetes es la sptima causa principal de muerte, sin embargo puede provocardiscapacidad permanente a causa de las complicaciones. Como enfermedadescardacas y accidentes cerebrovasculares, ceguera, enfermedad renal crnica yamputaciones.
El riesgo de sufrir accidentes cerebrovasculares es de 2 a 4 veces ms alto en laspersonas con diabetes.
La diabetes es la causa principal de ceguera entre los adultos de 20 a 74 aos deedad.Adems en personas con diabetes se realizan ms del 60% de las amputaciones notraumticas de las extremidades inferiores.
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