Efficacy of Metformin in Prevention of Glucocorticoid‐Induced Hyperglycemia in Patients Without Diabetes: A Meta‐Analysis
Sana Murtaza, Fatima Murtaza, M. Usama Yasin, Amna Shahid, Maira Shahid, Muhammad Maaz Bin Rehan, Fateen Ata, Muhammad Sohaib Asghar, Mohammed Mahmmoud Fadelallah EljackABSTRACT
Purpose
The glucocorticoids are increasingly being used in the management of different autoimmune conditions and cancers. Our meta‐analysis aims to leverage metformin's potential to reverse the metabolic complications of glucocorticoids by activating AMP‐activated protein kinase (AMPK), while sparing their anti‐inflammatory benefits.
Methods
PubMed, Cochrane Library, trial registries and Google Scholar were searched from inception to June 2025 for Randomized Controlled Trials (RCTs) and observational studies comparing metformin and placebo to prevent metabolic side effects of glucocorticoid therapy in non‐diabetic patients. After screening by two independent reviewers according to PRISMA guidelines, four studies involving 187 patients were analysed using the random‐effects model in RevMan 5.4.1, and mean differences (MD) were calculated.
Results
Preventive metformin administration during glucocorticoid treatment is superior to placebo with respect to glycaemic control as shown by statistically significant reduction in fasting blood glucose [MD = −0.60 (95% CI: −0.86 to −0.34)], HOMA index of insulin resistance [MD = −0.53 (95% CI: −0.97 to −0.08)], LDL levels [MD = −0.20 (95% CI: −0.40 to −0.00)] and total cholesterol [MD = −0.27 (95% CI: −0.54 to −0.01)]. However, our study failed to show significant improvement in area under the curve glucose (mmol/L × min) after challenge [MD = −176.66 (95% CI: −415.42, 62.11)], basal metabolic rate (BMR) [MD = 51.99 (95% CI: −53.08, 157.07)], HDL [MD = −0.04 (95% CI: −0.13, 0.05)], insulin levels [MD = −2.26 (95% CI: −5.90, 1.38)], triglycerides [MD = −0.15 (95% CI: −0.42, 0.13)] and body weight [MD = −0.93 (95% CI: −2.29 to 0.44)].
Conclusion
While glucocorticoids remain essential in various clinical contexts, their detrimental effects on glucose metabolism are well documented. This study supports metformin as a promising preventive treatment in non‐diabetic patients receiving systemic glucocorticoid therapy. Improvement in insulin sensitivity and resulting fasting glucose levels may offset glucocorticoid‐exacerbated inflammation. Further studies are needed to address long‐term outcomes, including adiposity, bone metabolism, appetite, liver function and muscle wasting, as well as to identify possible predictors of therapeutic response.
Trial Registration
International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD420251104082