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 μg 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.
RCT Entities:
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 μg 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.
Authors: Donald H Maurice; Hengming Ke; Faiyaz Ahmad; Yousheng Wang; Jay Chung; Vincent C Manganiello Journal: Nat Rev Drug Discov Date: 2014-04 Impact factor: 84.694
Authors: Diego J Maselli; Surya P Bhatt; Antonio Anzueto; Russell P Bowler; Dawn L DeMeo; Alejandro A Diaz; Mark T Dransfield; Ashraf Fawzy; Marilyn G Foreman; Nicola A Hanania; Craig P Hersh; Victor Kim; Gregory L Kinney; Nirupama Putcha; Emily S Wan; J Michael Wells; Gloria E Westney; Kendra A Young; Edwin K Silverman; MeiLan K Han; Barry J Make Journal: Chest Date: 2019-05-30 Impact factor: 9.410