Can Metformin Reduce Complications From Glucocorticoids?

A new study showed improved glycemia along with a host of other secondary benefits

Patients who are prescribed glucocorticoids such as prednisone often find the side effects troubling: abdominal weight gain, high blood pressure, high cholesterol, changes to bone density, and even cardiovascular damage.

Recent studies have found that metformin use among those taking such glucocorticoids reduces hyperglycemia. A new study that aimed to find out if metformin helped alleviate negative changes in fat distribution ended up discovering a wide array of secondary benefits instead.

New Metformin study

The study looked at 53 patients between 18 and 75 who had an inflammatory condition that required at least 20 mg of prednisone for more than 4 weeks and at least 10 mg for a further 12 weeks. Patients were randomized into a placebo group or a group that received metformin for 12 weeks.

The primary outcome, which was to improve the ratio of visceral to subcutaneous fat, was not acheived. However, the study authors found positive secondary outcomes which resulted from supplementing glucocorticoid treatment with meformin, including stabilization of:

  • Body Mass Index (BMI)
  • hip and waist circumference
  • blood pressure 
  • fasting glucose levels 
  • glucose challenge results 
  • tumor necrosis factor levels
  • lipid profile
  • C-reactive protein levels (CRP)
  • bone density
  • carotid artery thickness

Results

The metformin group also showed an array of secondary positive changes, including:

  • decrease in subcutaneous gut fat
  • decreased glucose and A1c levels
  • reduced insulin resistance
  • improved β cell function which accounts for better insulin secretion
  • improved total and LDL cholesterol
  • improved liver function
  • less hunger
  • increased hip bone density
  • decreased CRP
  • decreased infection rate

Conclusions

“This was a small short term study, but despite this we did see significant improvement in many parameters,” says study author Marta Korbonits, MD, Ph.D., a professor of endocrinology and metabolism at the London School of Medicine at Queen Mary University of London. 

W. Timothy Garvey, MD, a professor of medicine in the department of nutrition sciences at the University of Alabama and associate director of the Nutrition Obesity Research Center, says that results on some of the secondary outcomes weren’t surprising to him. “We know that metformin can improve both fasting glucose and glucose output," he confirms.

He adds that the authors reported that metformin use may have some anti-inflammatory capabilities, as shown by the decrease in CRP. It’s of interest, he says, along with the fact that there were fewer patients who developed pneumonia in the metformin group – just one as compared to nine in the control, suggesting lower infection rates.

“But I think that this is more hypotheses generating than proving. It’s very interesting, but it requires a study that is designed specifically to assess using metformin as a way to mitigate inflammation. And the lower infection rate could be due to better glycemic control, so that too needs more study,” says Garvey.

Garvey is unsure what to make of the secondary outcome of reduced carotid artery thickness. “The patients were treated for a short time, and I wonder if there was enough time on metformin for that to be a result. I’m skeptical.”

However, he believes there is an argument for physicians to prescribe metformin to patients who take glucocorticoids as there are other studies that indicate it can reduce cardiovascular events. If a patient is prediabetic, had gestational diabetes in pregnancy, had a family history of diabetes or other known risk factors, it might also be worth prophylactically putting a patient on metformin when they begin steroid use.

“When these patients do get diabetes, they are often harder to treat and need high doses of insulin, so it’s a reasonable thing to do, and data in this paper supports it. But the vascular, infection, and anti-inflammatory impacts are just hypotheses right now.”

This drug can benefit patients with diseases that require they take glucocorticoids for long periods of time, says Garvey. “It may not prevent weight gain, which patients might appreciate, but it can improve some very important test results.”

Upcoming research

Next, Korbonits says that she and her coauthors will conduct a larger study, using a wider patient population. That study will also include patients with different underlying diagnoses. “We need a larger study to prove this with more patients and also on other underlying diagnoses such as cancer. That’s a huge group of patients who go on large doses of glucocorticoids, with plenty of years of survival, so metabolic issues are very relevant,” she says.

 

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Cardiovascular Complications, Hypoglycemia Common in Older Patients with Diabetes
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