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J Clin Endocrinol Metab. 2012 Sep;97(9):E1720-5. doi: 10.1210/jc.2011-2886. Epub 2012 Jun 20.

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

Author information

  • 1Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands. e.wouters@mumc.nl

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 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.

PMID:
22723325
[PubMed - indexed for MEDLINE]
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