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Duloxetine’s Effect on Blood Glucose Levels

By: Neal Shah, Co-Editor-in-Chief

Duloxetine is a serotonin (5HT) and norepinephrine (NE) reuptake inhibitor (SNRI) introduced to the US market in 2004, indicated for the treatment of diabetic neuropathic pain.1 A chemical figure of duloxetine is shown [in the PDF].2

It was developed in an effort to mimic tricyclic antidepressant mitigation of neuropathic pain without the extensive systemic side effects that limit their use.1 Though duloxetine has not been shown to have any true neuroprotective effects, its combined SNRI effects contribute to pain cessation along the pain tracts in the central nervous system.1 An interesting finding during trials was that duloxetine apparently slightly worsened both glucose control and raised hemoglobin A1c (HbA1c), a marker of average blood glucose over a three-month period.1 The package insert reports an average glucose increase of 12 mg/dL and an increase of HbA1c by 0.5% compared to placebo in a 41 week study.3 A division of Novartis found in a meta-analysis of seven trials that while impairment of glucose control was significant, at the end of a 52 week trial, changes in plasma glucose and A1c were statistically insignificant.4 Another meta-analysis done by Abbott laboratories found that these changes indicated no enhanced disease progression.5

In conclusion, when counseling a diabetic patient about the effects of duloxetine, inform them that they may see a slight increase in their blood glucose and/or A1c, and that the benefits of possible neuropathic pain relief may outweigh this slight increase.


  1. Smith T and Nicholson R. Review of duloxetine in the management of diabetic peripheral neuropathic pain. Vasc Health Risk Manag. 2007 December; 3(6): 833—44.
  2. Duloxetine – Compound Summary. Available at: Accessed 15 September 2012.
  3. Eli Lilly and Company. Cymbalta (duloxetine) package insert. Accessed 8 September 2012.
  4. Crucitti A, Zhang Q, Nilsson M et al. Duloxetine treatment and glycemic controls in patients with diagnoses other than diabetic peripheral neuropathic pain: a meta-analysis. Curr Med Res Opin. 2010 Nov;26(11):2579—88. Epub 2010 Sep 27.
  5. Hall JA, Wang F, Oakes TM et al. Safety and tolerability of duloxetine in the acute management of diabetic peripheral neuropathic pain: analysis of pooled data from three placebo-controlled clinical trials. Expert Opin Drug Saf. 2010 Jul;9(4):525—37.
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