Does Duloxetine Cause Increased Blood Sugar in Diabetic Patients?
Duloxetine causes a small but statistically significant increase in fasting blood glucose and HbA1c in diabetic patients, but this effect is clinically minor and should not prevent its use for diabetic peripheral neuropathic pain. 1
Evidence from Clinical Trials in Diabetic Patients
The FDA drug label provides the most direct evidence on this question. In three clinical trials specifically enrolling diabetic patients with peripheral neuropathy (mean diabetes duration 12 years, baseline fasting glucose 176 mg/dL, baseline HbA1c 7.8%), duloxetine showed the following effects 1:
- During the 12-week acute treatment phase: Duloxetine was associated with a small increase in mean fasting blood glucose compared to placebo 1
- During the extension phase (up to 52 weeks): Mean fasting blood glucose increased by 12 mg/dL in the duloxetine group versus a decrease of 11.5 mg/dL in the routine care group 1
- HbA1c changes over 52 weeks: HbA1c increased by 0.5% in the duloxetine group versus 0.2% in the routine care group 1
Magnitude and Clinical Significance
While statistically significant, these glycemic changes are modest in magnitude. Multiple research studies confirm this pattern 2, 3:
- A 2007 review noted "a minor but statistically significant increase in blood glucose compared with placebo treated patients" in controlled clinical trials 3
- A 2011 review concluded that "duloxetine treatment had no clinically significant effect on glycemic control" 2
- Long-term studies (52 weeks) showed duloxetine "did not appear to adversely affect glycemic control" 4
Context: Non-Diabetic Populations
A meta-analysis examining duloxetine's effects in patients WITHOUT diabetic peripheral neuropathy (patients with anxiety, fibromyalgia, chronic low back pain, and depression) found 5:
- Short-term studies (9-27 weeks): No significant differences in fasting glucose or HbA1c between duloxetine and placebo 5
- Long-term studies: One 41-week study showed a small within-group HbA1c increase of 0.1%, but this was not reproduced in a 52-week placebo-controlled study 5
This suggests the glycemic effect may be more pronounced specifically in diabetic patients with neuropathy.
Clinical Recommendations
For diabetic patients with peripheral neuropathic pain, duloxetine remains a first-line treatment despite the modest glycemic effects 6:
- Duloxetine 60-120 mg daily is approved by both the FDA and European Medicines Agency specifically for diabetic peripheral neuropathic pain 6
- The glycemic changes observed (12 mg/dL fasting glucose increase, 0.5% HbA1c increase over 52 weeks) are manageable with standard diabetes medication adjustments 1
- The pain relief benefits typically outweigh the minor glycemic impact 2
Monitoring Strategy
For diabetic patients starting duloxetine 1:
- Monitor fasting blood glucose and HbA1c at baseline before starting duloxetine 1
- Recheck fasting glucose within 4-8 weeks of initiating therapy 1
- Measure HbA1c at 3-6 months to assess cumulative glycemic impact 1
- Adjust diabetes medications (insulin, oral agents) as needed to maintain glycemic targets 1
- Do not withhold duloxetine solely due to concerns about glycemic control in patients who would otherwise benefit from it 2
Key Clinical Pitfall to Avoid
Do not confuse the small glycemic worsening with a contraindication to duloxetine use. The FDA label explicitly states duloxetine "worsened glycemic control in some patients with diabetes" but does not list diabetes or poor glycemic control as a contraindication 1. The actual contraindications are severe hepatic disease, severe renal impairment (GFR <30 mL/min), and concomitant use with MAOIs or thioridazine 1.