Does Treatment With Duloxetine for Neuropathic Pain Impact Glycemic Control?

Abstract

OBJECTIVE -We examined changes in metabolic parameters in clinical trials of duloxetine for diabetic peripheral neuropathic pain (DPNP).RESEARCH DESIGN AND METHODS -Data were pooled from three similarly designed clinical trials. Adults with diabetes and DPNP (n ϭ 1,024) were randomized to 60 mg duloxetine q.d., 60 mg b.i.d., or placebo for 12 weeks. Subjects (n ϭ 867) were re-randomized to 60 mg duloxetine b.i.d. or routine care for an additional 52 weeks. Mean changes in plasma glucose, lipids, and weight were evaluated. Regression and subgroup analyses were used to identify relationships between metabolic measures and demographic, clinical, and electrophysiological parameters.RESULTS -Duloxetine treatment resulted in modest increases in fasting plasma glucose in short-and long-term studies (0.50 and 0.67 mmol/l, respectively). A1C did not increase in placebo-controlled studies; however, a greater increase was seen relative to routine care in long-term studies (0.52 vs. 0.19%). Short-term duloxetine treatment resulted in mean weight loss (Ϫ1.03 kg; P Ͻ 0.001 vs. placebo), whereas slight, nonsignificant weight gain was seen in both duloxetine and routine care groups with longer treatment. Between-group differences were seen for some lipid parameters, but these changes were generally small. Metabolic changes did not appear to impact improvement in pain severity seen with duloxetine, and nerve conduction was also not significantly impacted by treatment.CONCLUSIONS -Duloxetine treatment was associated with modest changes in glycemia in patients with DPNP. Other metabolic changes were limited and of uncertain significance. These changes did not impact the significant improvement in pain observed with duloxetine treatment. Diabetes Care 30:21-26, 2007N europathy is the most common diabetic microvascular complication, affecting up to 50% of all individuals with diabetes (1). Substantial morbidity is associated with diabetic peripheral neuropathy (DPN), which is the leading risk factor for diabetic foot complications and nontraumatic amputations. Though these late complications frequently occur in the insensate foot, symptomatic DPN also significantly impacts quality of life (2,3). Estimates of the prevalence of diabetic peripheral neuropathic pain (DPNP) vary from 3% to Ͼ20% (4).For many agents, the data supporting effectiveness is limited. In addition, nearly all treatments are associated with safety or tolerability issues. One category of side effects common to a number of the antidepressant and anticonvulsant drugs is related to metabolic changes. Weight gain is seen with tricyclic antidepressants (TCAs) (5) and anticonvulsants (e.g., valproate, gabapentin, pregabalin) (6). Changes in plasma glucose have also been reported with TCAs (7,8) and phenytoin (9), and dyslipidemia can be seen with carbamazepine (10).Duloxetine has demonstrated efficacy in several large clinical trials of DPNP (11-13) and is one of only two drugs to have received regulatory approval for the treatment of this condition. As a selective reupt...

Diabetic Neuropathy: A Position Statement by the American Diabetes Association

“…Duloxetine was also suggested to induce improvement in neuropathy-related quality of life (100). In longer-term studies, a small increase in A1C was reported in people with diabetes treated with duloxetine compared with placebo (102). Adverse events may again be more severe in older people but may be attenuated with lower doses and progressive titrations of duloxetine.…”

“…Both venlafaxine and duloxetine (see above) inhibit the reuptake of serotonin and norepinephrine without the muscarinic, histaminic, and adrenergic side effects that accompany the use of the tricyclic agents (98)(99)(100)102). However, the level of evidence for pain reduction associated with DSPN is higher with duloxetine (see above).…”

Clinical Outcomes of Electrodiagnostic Testing Conducted in Primary Care

“…11 Because this technology standardizes and automates NCSs up to the point of diagnostic interpretation (which is performed by the physician), data quality is essentially independent of clinical setting. This property has led to use of computerized EDX instrumentation in multicenter drug registration trials 12 and large-scale epidemiologic studies. 13,14 Further, because of inherent consistency, the accuracy of the results as assessed in controlled clinical studies should translate to clinical practice.…”

Depressão e diabetes mellitus

“…A tendência à melhora dos níveis de hemoglobina glicosilada com o uso da fluoxetina foi confirmada por outros estudos, mas não foi verificada com o uso de paroxetina em pelo menos dois estudos 24,25 .…”

“…A interferência da duloxetina no controle glicêmi-co foi avaliada em estudo voltado para tratamento de neuropatia diabética 25 . Os pacientes que utilizaram duloxetina tiveram discreto aumento da glicemia de jejum a curto e longo prazos, sem aumento da hemoglobina glicosilada.…”