Does prednisone (corticosteroid) cause weight gain?

Prednisone and Weight Gain

Yes, prednisone causes weight gain in a dose-dependent manner, with approximately 20% of patients reporting weight gain at doses ≥5 mg/day compared to <10% at doses <5 mg/day, and the effect is most pronounced in the first 9 months of treatment. 1

Dose-Response Relationship

The risk of weight gain increases significantly with higher cumulative doses:

• At doses <5 mg/day: Less than 10% of patients report weight gain 1
• At doses 5-7.5 mg/day: Approximately 22% report weight gain 1
• At doses >7.5 mg/day: Approximately 21% report weight gain 1
• Cumulative doses >1.7 grams: Significantly increased odds of weight gain, with OR 1.42 (95% CI 1.08-1.85) at 1.7-2.8 grams, escalating to OR 2.20 (95% CI 1.65-2.95) at cumulative doses >4.7 grams 1

The magnitude of weight gain typically ranges from 1.3 to 4.7 kg over treatment periods of 6 months to 2 years, depending on dose and duration. 1

Timeline of Weight Gain

Weight gain occurs predominantly in the first 9 months after initiation and then plateaus. 1, 2

• Multiple trials demonstrate that weight gain occurs early after glucocorticoid initiation, with the WGET trial showing weight gain in the first 9 months that plateaued through 1 year of follow-up 1
• The COBRA trial showed significantly higher weight gain in the prednisolone group at 26 weeks but not at 56 weeks, suggesting a plateau effect 1
• Patients treated for ≤1 year had a mean weight increase of 2.7 kg, while those treated >1 year had lower mean weight at last visit compared to baseline 1

Mechanism of Weight Gain

Prednisone induces weight gain through metabolic alterations rather than simple fluid retention:

• Decreased lipid oxidation: Prednisone significantly reduces fat oxidation (0.46 ± 0.39 mg/kg/min with prednisone vs. 1.06 ± 0.32 mg/kg/min without steroids in fasting state) 3
• Increased protein oxidation: Protein breakdown is significantly higher in patients on prednisone 3
• Increased muscle mass: The beneficial effect of prednisone at 0.75 mg/kg/day is associated with a 36% increase in muscle mass, though this comes with weight gain and growth retardation 4

These metabolic effects are not observed with budesonide, which has 90% first-pass hepatic metabolism and causes fewer systemic effects. 5, 3

Reversibility After Discontinuation

Weight loss occurs after prednisone discontinuation, but the timeline varies:

• One study showed patients who received 7.5 mg prednisolone for 2 years lost an average of 3.1 kg one year after discontinuation, while the placebo group gained 1.5 kg 1
• In patients who achieved remission, weight gained during the first year was maintained at 2-year follow-up 1

Clinical Impact and Quality of Life

Over 40% of patients with rheumatoid arthritis consider weight gain the "most bothersome in everyday life" adverse effect attributed to glucocorticoids, more than other listed side effects. 1

The clinical significance extends beyond cosmetic concerns:

• Obesity increases risk of type 2 diabetes, cancer, and cardiovascular disease 1
• Weight gain negatively impacts body image and self-esteem 1
• Concern about weight gain may reduce medication adherence, leading to inadequate disease control 1

Short-Term vs. Long-Term Use

Short-term use (10 days) does not cause significant weight gain:

• A randomized controlled trial of 10-day prednisolone (50 mg) in adults with stable asthma showed no significant changes in body weight (kg) [Coef. -0.38,95% CI: (-0.81,0.05) P = 0.083] or body fat (%) [Coef. -0.31,95% CI: (-0.81,0.20) P = 0.230] 6
• No difference in dietary intake, appetite measured by visual analogue scale, or serum leptin levels was observed 6

This suggests that weight gain is primarily a concern with prolonged therapy rather than brief courses for acute exacerbations.

Common Pitfalls and Management Strategies

Critical pitfall: Failing to counsel patients about expected weight gain leads to non-adherence and treatment failure. 1

Prevention strategies:

• Use the lowest effective dose, as weight gain risk increases substantially at doses ≥5 mg/day 1
• Consider steroid-sparing agents early, particularly in pediatric patients where growth and bone development are concerns 5
• In women with Crohn's disease on prednisone, a low-fat/high-protein diet may counteract the decreased lipid oxidation and increased protein catabolism 3
• Monitor weight at baseline and regularly during treatment (>2 kg gain in a month or ≥7% increase from baseline warrants intervention) 2
• Screen for steroid-related complications including weight gain, glucose intolerance, and hypertension 7

Alternative approach: Budesonide 9 mg daily may be considered for non-cirrhotic patients with certain conditions, as it causes fewer systemic side effects including less weight gain due to 90% first-pass hepatic metabolism. 5