Effect of the phosphodiesterase 4 inhibitor roflumilast on glucose metabolism in patients with treatment-naive, newly diagnosed type 2 diabetes mellitus.
BACKGROUND
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.


METHODS
We conducted a 12-wk, randomized, double-blind, placebo-controlled multicenter study with outpatients.


METHODS
Patients (n = 205) with newly diagnosed type 2 diabetes mellitus (DM2) but without COPD were included in the study.


METHODS
Roflumilast 500 μg or placebo was administered once daily.


METHODS
We evaluated mean change in blood glycated hemoglobin levels.


RESULTS
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).


CONCLUSIONS
Roflumilast lowered glucose levels in patients with newly diagnosed DM2 without COPD, suggesting positive effects on glucose homoeostasis.
Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands. e.wouters@mumc.nl
E F M
EF
Wouters
D
D
Bredenbröker
P
P
Teichmann
M
M
Brose
K F
KF
Rabe
L M
LM
Fabbri
B
B
Göke
D000328:Adult; D000368:Aged; D000631:Aminopyridines / Q000494:pharmacology*; D019540:Area Under Curve; D001549:Benzamides / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002096:C-Peptide / Q000097:blood; D003521:Cyclopropanes / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004311:Double-Blind Method; D005215:Fasting / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D005990:Glycerol / Q000097:blood; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications; D018401:Sample Size
D000631:Aminopyridines; D001549:Benzamides; D001786:Blood Glucose; D002096:C-Peptide; D003521:Cyclopropanes; D005230:Fatty Acids, Nonesterified; D005934:Glucagon; D005947:Glucose; D006442:Glycated Hemoglobin; D005990:Glycerol; D007328:Insulin; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast