Duloxetine treatment and glycemic controls in patients with diagnoses other than diabetic peripheral neuropathic pain: a meta-analysis

Abstract

Objective:

Mood disorders are often associated with poor glycemic control, and antidepressant treatments for mood and pain disorders can alter plasma glucose levels in patients with diabetes. A previous meta-analysis from three studies showed that duloxetine modestly increased fasting plasma glucose (FPG) and HbA_1c levels in patients with diabetic peripheral neuropathic pain (DPNP). This meta-analysis examined whether there were any short- and long-term effects of duloxetine (20–120 mg/day) on glycemic control in patients with diagnoses other than DPNP.

Research design and methods:

Short-term data (9–27 weeks): seven studies of duloxetine in general anxiety disorder, fibromyalgia, and chronic lower back pain (CLBP). Long-term data: 41-week, uncontrolled extension of the short-term CLBP study and 52-week study in patients with recurrence of major depressive disorder.

Main outcome measures:

Baseline-to-endpoint changes in FPG and HbA_1c levels.

Results:

In short-term studies, patients were randomly assigned to placebo (n = 1098) or duloxetine (n = 1563). Mean baseline-to-endpoint changes in FPG and HbA_1c did not significantly differ in duloxetine-treated patients compared with placebo-treated patients. In the 41-week study (n = 181), duloxetine-treated patients experienced a small but significant within-group baseline-to-endpoint increase in HbA_1c (mean change = 0.1%; p < 0.001). This result was in contrast to absence of effect on mean baseline-to-endpoint within-group changes in FPG (p = 0.326) in that study, and to absence of between-treatment changes in FPG (p = 0.744) and HbA_1c (p = 0.180) in the 52-week placebo-controlled study.

Conclusion:

Duloxetine treatment did not significantly alter FPG and HbA_1c levels compared with placebo treatment in the short-term studies. A small but statistically significant within-group increase in HbA_1c was found in the 41-week study, but not in between-treatment group differences in the 52-week study. Neither of the long-term studies showed significant changes in the FPG levels. The small, non-reproducible HbA_1c increase in one study of patients without DPNP may have resulted from patients with unrecognized diabetes in these trials.

Key words:

• Diabetes
• Diabetic peripheral neuropathic pain
• Duloxetine
• Fasting plasma glucose
• HbA_1c
• SNRI

Transparency

Declaration of funding

Funding was provided by Eli Lilly and Company and Boehringer Ingelheim GmbH.

Declaration of financial/other relationships

All authors except A.C, C.Y., and S.B. are employees of Eli Lilly and Company and are stock holders of the company. A.C. and C.Y. were employees of Eli Lilly when the manuscript was being written. S.B. is an employee of Boehringer Ingelheim GmbH, Germany. The peer reviewers may receive honoraria from CMRO for their review work. Peer reviewer 1 has disclosed that he/she is a recipient of sponsorship funding and research/grant funding from and is a consultant/advisor to Amgen, Alcon, Wyeth, Merck & Co. Inc., Ipsen, Pneuma Partners, Kinex, Endo, Sanofi-Pasteur, Nycomed, and Encysive.