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.