Nuevos Aspectos en el Tratamiento de la Diabetes Mellitus Tipo 2

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Abstract

La Diabetes Mellitus es una de las enfermedades más frecuentes en todo el mundo y un problema de salud pública debido a sus complicaciones crónicas y agudas. En los Estados Unidos, actualmente se encuentran en el mercado, cinco tipos de agentes orales cada uno con un mecanismo diferente de acción para mejorar el control glucémico en pacientes con diabetes tipo 2. El Estudio Prospectivo sobre Diabetes concluido en el Reino Unido (UKPDS), ha demostrado que la diabetes mellitus tipo 2 es un desorden progresivo que puede ser tratado inicialmente con monoterapia con un agente oral y eventualmente requiere la adición de otros agentes orales, y que en muchos pacientes se requiere la terapia con insulina para lograr los niveles glucémicos deseados. En el UKPDS, el control glucémico mejorado, independientemente del agente utilizado (sulfonilureas, biguanidas o insulina), disminuyó la incidencia de complicaciones microvasculares (retinopatía, neuropatía y nefropatía) y macrovasculares. Esta revisión examina la terapia antihiperglucémica y el mecanismo de acción, eficacia y los beneficios no-glucémicos de los cinco tipos de agentes orales de uso en la actualidad.

Translated abstract

Diabetes mellitus is one of the most frequent diseases all over the world and is a public health problem due its acute and chronic complications. Actually, there are five different oral drugs regarding glycemic control in Type 2 Diabetes available in the United States, each one with a distinct mechanism of action. The finished United Kingdom Prospective Diabetes Study (UKPDS), has demonstrated that Type 2 Diabetes is a progressive disorder that can be initially treated with an oral agent monoterapy, but eventually will require the addition of another agent, and in many patients, will be needed insulin therapy to achieve satisfactory glycemic levels. In the UKPDS the improved glycemic control, unrelated of the employed agent (sulfonylureas, biguanides or insulin), diminished the incidence of microvascular (retinopathy, neuropathy and nephropathy) and macrovascular complications. This review examines the antithyperglycemic therapy and mechanism of action, efficacy, and the non-glycemic benefits of the five oral agents actually in use.

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Most cited references 190

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Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus

(2002)

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Metabolic effects of metformin in non-insulin-dependent diabetes mellitus.

M. Stumvoll, N Nurjhan, G Perriello … (1995)

The metabolic effects and mechanism of action of metformin are still poorly understood, despite the fact that it has been used to treat patients with non-insulin-dependent diabetes mellitus (NIDDM) for more than 30 years. In 10 obese patients with NIDDM, we used a combination of isotope dilution, indirect calorimetry, bioimpedance, and tissue-balance techniques to assess the effects of metformin on systemic lactate, glucose, and free-fatty-acid turnover; lactate oxidation and the conversion of lactate to glucose; skeletal-muscle glucose and lactate metabolism; body composition; and energy expenditure before and after four months of treatment. Metformin treatment decreased the mean (+/- SD) glycosylated hemoglobin value from 13.2 +/- 2.2 percent to 10.5 +/- 1.6 percent (P < 0.001) and reduced fasting plasma glucose concentrations from 220 +/- 41 to 155 +/- 28 mg per deciliter (12.2 +/- 0.7 to 8.6 +/- 0.5 mmol per liter) (P < 0.001). Although resting energy expenditure did not change, the patients lost 2.7 +/- 1.3 kg of weight (P < 0.001), 88 percent of which was adipose tissue. The mean (+/- SE) rate of plasma glucose turnover (hepatic glucose output and systemic glucose disposal) decreased from 2.8 +/- 0.2 to 2.0 +/- 0.2 mg per kilogram of body weight per minute (15.3 +/- 0.9 to 10.8 +/- 0.9 mumol per kilogram per minute) (P < 0.001), as a result of a decrease in hepatic glucose output; systemic glucose clearance did not change. The rate of conversion of lactate to glucose (gluconeogenesis) decreased by 37 percent (P < 0.001), whereas lactate oxidation increased by 25 percent (P < 0.001). There were no changes in the plasma lactate concentration, plasma lactate turnover, muscle lactate release, plasma free-fatty-acid turnover, or uptake of glucose by muscle. Metformin acts primarily by decreasing hepatic glucose output, largely by inhibiting gluconeogenesis. It also seems to induce weight loss, preferentially involving adipose tissue.

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Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.

R DeFronzo, A M Goodman (1995)

Sulfonylurea drugs have been the only oral therapy available for patients with non-insulin-dependent diabetes mellitus (NIDDM) in the United States. Recently, however, metformin has been approved for the treatment of NIDDM. We performed two large, randomized, parallel-group, double-blind, controlled studies in which metformin or another treatment was given for 29 weeks to moderately obese patients with NIDDM whose diabetes was inadequately controlled by diet (protocol 1: metformin vs. placebo; 289 patients), or diet plus glyburide (protocol 2: metformin and glyburide vs. metformin vs. glyburide; 632 patients). To determine efficacy we measured plasma glucose (while the patients were fasting and after the oral administration of glucose), lactate, lipids, insulin, and glycosylated hemoglobin before, during, and at the end of the study. In protocol 1, at the end of the study the 143 patients in the metformin group, as compared with the 146 patients in the placebo group, had lower mean (+/- SE) fasting plasma glucose concentrations (189 +/- 5 vs. 244 +/- 6 mg per deciliter [10.6 +/- 0.3 vs. 13.7 +/- 0.3 mmol per liter], P < 0.001) and glycosylated hemoglobin values (7.1 +/- 0.1 percent vs. 8.6 +/- 0.2 percent, P < 0.001). In protocol 2, the 213 patients given metformin and glyburide, as compared with the 210 patients treated with glyburide alone, had lower mean fasting plasma glucose concentrations (187 +/- 4 vs. 261 +/- 4 mg per deciliter [10.5 +/- 0.2 vs. 14.6 +/- 0.2 mmol per liter], P < 0.001) and glycosylated hemoglobin values (7.1 +/- 0.1 percent vs. 8.7 +/- 0.1 percent, P < 0.001). The effect of metformin alone was similar to that of glyburide alone. Eighteen percent of the patients given metformin and glyburide had symptoms compatible with hypoglycemia, as compared with 3 percent in the glyburide group and 2 percent in the metformin group. In both protocols the patients given metformin had statistically significant decreases in plasma total and low-density lipoprotein cholesterol and triglyceride concentrations, whereas the values in the respective control groups did not change. There were no significant changes in fasting plasma lactate concentrations in any of the groups. Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone.

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Author and article information

Contributors

F Contreras: Role: ND

S Jiménez: Role: ND

M García: Role: ND

J Rocafull: Role: ND

E Montero: Role: ND

M González: Role: ND

N Ospino: Role: ND

S Rodríguez: Role: ND

C Fouilloux: Role: ND

A Bolívar: Role: ND

Y Lezama: Role: ND

M Velasco: Role: ND

Journal

Journal ID (publisher): avft

Title: Archivos Venezolanos de Farmacología y Terapéutica

Abbreviated Title: AVFT

Publisher: Sociedad Venezolana de Farmacológia y Farmacológia Clínica y Terapéutica. Escuela de Medicina (Caracas )

ISSN: 0798-0264

Publication date (Print): February 2001

Volume: 20

Issue: 1

Pages: 6-26

Affiliations

[1 ] UCV

[2 ] EEE

[3 ] HVSR

[4 ] UCV

[5 ] Medico Interno

[6 ] UCV

[7 ] UCV

Article

Publisher ID: S0798-02642001000100002

SO-VID: 132e0d71-16a8-4130-8206-0433186c7834

License:

http://creativecommons.org/licenses/by/4.0/

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SciELO Venezuela

Self URI (journal page): http://www.scielo.org.ve/scielo.php?script=sci_serial&pid=0798-0264&lng=en

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Receptores Sur y Sulfonilureas en el tratamiento de la Diabetes Mellitus Tipo 2
Authors: F. Contreras, B. Romero, N. Suárez …

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Nuevos Aspectos en el Tratamiento de la Diabetes Mellitus Tipo 2

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SciELO Venezuela

Most cited references 190

Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus

Metabolic effects of metformin in non-insulin-dependent diabetes mellitus.

Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.

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Cited by 1

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