Does pregabalin cause weight gain?

Does Pregabalin Cause Weight Gain?

Yes, pregabalin definitively causes weight gain as a recognized adverse effect, with approximately 9% of patients experiencing ≥7% weight gain over baseline in controlled trials, compared to only 2% with placebo. 1

Evidence from FDA Drug Labeling

The FDA-approved prescribing information explicitly identifies weight gain as a significant adverse effect of pregabalin treatment 1:

• In controlled trials up to 14 weeks, 9% of pregabalin-treated patients gained ≥7% of baseline weight versus 2% of placebo patients 1
• Weight gain is dose-related and duration-dependent, occurring regardless of baseline BMI, gender, or age 1
• Among diabetic patients specifically, pregabalin-treated patients gained an average of 1.6 kg (range: -16 to 16 kg) compared to 0.3 kg in placebo patients 1
• In a cohort of 333 diabetic patients receiving pregabalin for ≥2 years, the average weight gain was 5.2 kg 1

Clinical Guideline Recommendations

Multiple authoritative guidelines explicitly list pregabalin among anticonvulsants associated with weight gain:

• The American Diabetes Association's 2021 Standards of Care specifically names pregabalin as a medication associated with weight gain and recommends minimizing such medications when treating patients with type 2 diabetes and obesity 2
• Guidelines for painful diabetic peripheral neuropathy identify weight gain as one of the most frequent side effects of pregabalin, alongside dizziness, somnolence, peripheral edema, and headache 2

Quantifying the Weight Gain Risk

Research data provides more granular detail on weight gain patterns 3:

• The majority of patients (81.8%) maintained weight within ±7% of baseline over 1 year of treatment 3
• 14.5% were "delayed weight gainers" (exceeding 7% weight gain after 2 months but not initially) 3
• 2.6% were "early weight gainers" (exceeding 7% weight gain within the first 2 months) 3
• Overall weight gainers experienced median weight increases of 6.20 kg (9.12% change) for delayed gainers and 5.46 kg (13.9% change) for early gainers 3

Comparative Risk and Dose Effects

• Pregabalin combined with duloxetine produces greater weight gain than either agent alone, with combination therapy associated with +8.5 lb weight gain after >12 months versus +3.6 lb for pregabalin monotherapy 4
• Higher doses of pregabalin (>300 mg/day) are associated with significantly more weight gain (+6.5 lb) compared to lower doses 4
• There is a positive correlation between increasing pregabalin dose and weight gain (r = 0.42, P = 0.045) 5

Clinical Context and Management

Weight gain from pregabalin is not associated with peripheral edema in all cases 1:

• Weight gain occurs independently of edema formation 1
• However, when pregabalin is combined with thiazolidinedione antidiabetic agents, both peripheral edema (19% vs 8% for pregabalin alone) and weight gain (7.5% vs 4% for pregabalin alone) increase substantially 1

Important Caveats

• Weight gain led to treatment discontinuation in only 0.3% of patients in controlled trials, suggesting most patients tolerate this side effect 1
• In diabetic patients, pregabalin-associated weight gain did not appear to cause loss of glycemic control as measured by HbA1c in clinical trials 1
• The long-term cardiovascular effects of pregabalin-associated weight gain remain unknown 1

Practical Recommendations

When prescribing pregabalin, clinicians should 2:

• Counsel patients about the realistic risk of weight gain before initiating therapy
• Monitor weight regularly, particularly in patients with diabetes, obesity, or cardiovascular risk factors
• Consider minimizing or avoiding pregabalin in patients where weight gain would be particularly problematic
• Avoid combining pregabalin with thiazolidinediones when possible due to synergistic effects on weight and edema 1