For people on systemic glucocorticoid therapy for various chronic inflammatory conditions, concomitant metformin seemed to provide some overall health benefits, a phase II trial found.
In a small analysis of patients with an inflammatory disease treated with steroids, but without preexisting diabetes, daily metformin for 12 weeks did not significantly improve visceral-to-subcutaneous fat area ratio (difference within metformin group 0.11), which was the study’s primary outcome, reported Márta Korbonits, MD, of the University of London, and colleagues.
However, metformin did help to slightly improve many other factors, including a significant reduction in truncal subcutaneous fat compared with placebo (-3,835 mm², 95% CI -6781 to -888, P=0.01), they stated in the Lancet Diabetes & Endocrinology.
Visceral adiposity, waist circumference, and body weight weren’t significantly affected, the authors added, although several other metabolic markers — including markers of carbohydrates, lipids, liver, and bone metabolism — all showed some improvements with concomitant metformin.
These benefits included improvement in fasting glucose, HbA1c, HOMA2IR, total and LDL cholesterol concentrations, intima-media thickness, bone mineral density at the hip, and a decrease in the bone resorption marker βCTX.
Beyond improvements in the metabolic profile, metformin also showed a significant improvement in the overall quality of health for these patients on continuous prednisolone. Compared with those on placebo, metformin significantly cut down on the frequency of pneumonia infections experienced by these patients, at one versus seven events, and also cut down on the amount of moderate-to-severe infections at two vs 11 events.
Hospital admission due to adverse events (AEs) were also significantly lower among those treated with metformin at one versus nine admissions. The most common AEs were nausea, diarrhea, and abdominal discomfort.
One downside to metformin treatment was a higher frequency of diarrhea events versus placebo (18 events vs eight events, P=0.01).
“Our findings are strikingly positive and suggest that a simple and immediately available intervention, treatment with the diabetes drug metformin, can improve the clinical status of patients on glucocorticoid treatment, even if they do not have diabetes,” Korbonits explained in a statement. “The results could have a huge impact on the large number of patients on long-term glucocorticoids, improving treatment-related complications and their cardiovascular prognosis.”
“Whilst developed countries may be increasing the use of biologics or other steroid-sparing agents, in many other parts of the world there’s still a heavy reliance on glucocorticoids,” she pointed out, underscoring the need for “a safe, cheap, and effective treatment that can prevent the major metabolic complications of these medicines, but does not affect, or could even improve, their anti-inflammatory properties.”
The analysis included 40 adults with an inflammatory disease treated with continuous prednisolone at 20 mg/day or more for at least 4 weeks, and who remained on at least 10 mg/day for the following 12 weeks. Metformin was administered to 19 of these individuals, at a starting dose of 850 mg/day for the first 5 days, bumping up to 850 mg twice a day for the next 5 days, and ending with 850 mg three times a day for the remaining of the 12 weeks. They were then compared with 21 patients on placebo. None of these patients had preexisting diabetes.
In an accompanying comment, Martin Reincke, MD, PhD, of the Ludwig Maximilian University of Munich in Germany, stated that the “stunning efficacy of metformin on these surrogate parameters might call for immediate action.”
However, he pointed out the very small sample size and short duration limited these findings, and that a larger, phase III trial would be needed before any changes to clinical practice are made.
Reincke stated that it “has to be shown that metformin is not an ambiguous agent interfering with the anti-inflammatory and immunosuppressive effects of glucocorticoids,” explaining that although there were no flairs of inflammatory disease reported among these trial participants on metformin, the decrease in pneumonia cases “might indicate a complex interaction with the immune system.”
Until these questions are answered, Reincke advised use of metformin in this setting be given on a case-by-case basis.
The trial was funded by Barts Charity and Merck Serono.
Korbonits disclosed relevant relationships with Merck Serono, Barts Charity, and Novo Nordisk. Co-authors disclosed multiple relevant relationshiops with industry.
Reincke disclosed support from the Else Kröner-Fresenius Stiftung and the Deutsche Forschungsgemeinschaft.