TY - JOUR
T1 - Effect of the phosphodiesterase 4 inhibitor roflumilast on glucose metabolism in patients with treatment-naive, newly diagnosed type 2 diabetes mellitus
AU - Wouters, E.F.M.
AU - Bredenbröker, D.
AU - Teichmann, P.
AU - Brose, M.
AU - Rabe, K.F.
AU - Fabbri, L.M.
AU - Goke, B.
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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 AND SETTING: 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 mug or placebo was administered once daily. PRIMARY OUTCOME: We evaluated mean change in blood glycated hemoglobin levels. SECONDARY OUTCOMES: 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.
AB - 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 AND SETTING: 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 mug or placebo was administered once daily. PRIMARY OUTCOME: We evaluated mean change in blood glycated hemoglobin levels. SECONDARY OUTCOMES: 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.
U2 - 10.1210/jc.2011-2886
DO - 10.1210/jc.2011-2886
M3 - Article
C2 - 22723325
SN - 0021-972X
VL - 97
SP - E1720-E1725
JO - Journal of Clinical Endocrinology & Metabolism
JF - Journal of Clinical Endocrinology & Metabolism
IS - 9
ER -