Effect of the phosphodiesterase 4 inhibitor roflumilast on glucose metabolism in patients with treatment-naive, newly diagnosed type 2 diabetes mellitus.
J Clin Endocrinol Metab
; 97(9): E1720-5, 2012 Sep.
Article
en En
| MEDLINE
| ID: mdl-22723325
ABSTRACT
CONTEXT The phosphodiesterase 4 inhibitor roflumilast is a first-in-class antiinflammatory treatment for severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis and a history of frequent exacerbations. In previous clinical studies, a transient and reversible weight decrease was reported with roflumilast, suggesting the systemic actions of this drug may impact metabolism. OBJECTIVE:
Our objective was to investigate the effects of roflumilast on glucose homeostasis and body weight. DESIGN ANDSETTING:
We conducted a 12-wk, randomized, double-blind, placebo-controlled multicenter study with outpatients. PATIENTS Patients (n = 205) with newly diagnosed type 2 diabetes mellitus (DM2) but without COPD were included in the study.INTERVENTIONS:
Roflumilast 500 µg or placebo was administered once daily. PRIMARYOUTCOME:
We evaluated mean change in blood glycated hemoglobin levels. SECONDARYOUTCOMES:
We also evaluated mean change from baseline in the postmeal area under the curve (AUC) for a range of metabolic parameters.RESULTS:
Roflumilast was associated with a significantly greater reduction in glycated hemoglobin levels than placebo (least square mean = -0.45%; P < 0.0001) in patients with DM2. In the roflumilast group, postmeal AUC decreased significantly from baseline to last visit for free fatty acids, glycerol, glucose, and glucagon, whereas they slightly increased for C-peptide and insulin. In contrast to roflumilast, the glucagon AUC increased with placebo, and the insulin AUC decreased. Between-treatment analysis revealed statistically significant differences in favor of roflumilast for glucose (P = 0.0082), glycerol (P = 0.0104), and C-peptide levels (P = 0.0033). Patients in both treatment groups lost weight, although the between-treatment difference of the changes from baseline to last visit [-0.7 (0.4) kg] was not statistically significant (P = 0.0584).CONCLUSION:
Roflumilast lowered glucose levels in patients with newly diagnosed DM2 without COPD, suggesting positive effects on glucose homoeostasis.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Benzamidas
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Diabetes Mellitus Tipo 2
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Inhibidores de Fosfodiesterasa 4
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Glucosa
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Aminopiridinas
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Prognostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2012
Tipo del documento:
Article
País de afiliación:
Países Bajos