Could metformin counteract steroid side effects?

A newly published review article has shown that metformin is effective at reversing some of the weight gain associated with certain antipsychotic medications and helping control blood sugar.

Another article, from 2012, presents a study of muscular dystrophy patients treated with glucocorticoid steroids. When metformin was given, weight gain ceased and began to be reversed.

Any thoughts as to whether this might apply as well to patients with autoimmune diseases to prevent and/or treat these same side effects when they result from taking steroids? How might we get the necessary research done?

Metformin is an old, inexpensive medication ($4.00 prescription at Walmart) used to treat type II diabetes. It is relatively safe, and in fact there are claims that it helps to slow the aging process and extend life expectancy.

europepmc.org/abstract/med/26417824
A review of the evidence for the use of metformin in the treatment of metabolic syndrome caused by antipsychotics.
(PMID:26417824)
Jesus C, Jesus I, Agius M
Charles University in Prague, Third Faculty of Medicine, Prague, Czech Republic, catia_vicky@hotmail.com.
Psychiatria Danubina [2015, 27 Suppl 1:S489-91]
Type: Journal Article

Abstract

Psychiatric patients requiring therapy with antipsychotics have a greater incidence of becoming overweight or obese compared with the general population. Many of these patients are often treated with second-generation (atypical) antipsychotics (SGAs), which are associated with weight gain, dyslipidaemia, and other metabolic derangements. The most important and first line of treatment for the metabolic syndrome is lifestyle changes including diet and exercise. However, other approaches like the use of medication (e.g. Metformin) have been also used, mainly when the lifestyle changes are difficult to achieve. Therefore, the treatment of antipsychotic-induced weight gain with metformin may be an option after the lifestyle and dietary changes fail. The use of metformin is still experimental and off license regarding the treatment of metabolic syndrome in Psychiatric patients, however we wished to assess the evidence for its use.Our study is a literature based research. For our research we reviewed 12 Pubmed published articles from 2006 to 2013.Metformin have been reported to counteract effectively antipsychotic-induced body weight gain and has been demonstrated to improve glycaemic control and promote a moderate weight loss in both diabetic and non-diabetic subjects. Metformin use appears to be a benefit when started early in the course of treatment and mostly in young adults newly exposed to antipsychotic drugs.

www.sciencedirect.com/science/article/pii/S0960896612003938
T.P.51 Metformin reduces weight and BMI in Duchenne muscular dystrophy patients on long term glucocorticoid therapy

S.E. Weatherspoon, J. Collins, H. Sucharew, B.L. Wong, I. Rybalsky, S.R. Rose, D.J. Klein, M.M. Rutter
doi:10.1016/j.nmd.2012.06.211


Obesity is a significant problem in Duchenne muscular dystrophy (DMD) due to glucocorticoid (GC) therapy and motor decline. Excessive weight gain can further impair mobility, increase risk for diabetes and cardiopulmonary disease, and affect quality of life. Metformin improves weight and insulin resistance in obesity and type 2 diabetes. To determine if metformin reduces weight and BMI in DMD patients on long term GC who have excessive weight gain and insulin resistance. This was a retrospective case series of DMD boys on daily GC therapy who were treated with metformin for excessive weight gain and insulin resistance. Primary outcomes were rate of weight gain and BMI pre and post starting metformin. Weight and BMI measurements were collected 1 year prior, at initiation of metformin, and 6 and 12 months post. Generalized linear models for the vector of weight and BMI measurements over time were fit using generalized estimating equations. Forty-five DMD patients (mean age 12.7 ± 3.1 y) were studied. Patients had insulin resistance by glucose tolerance testing. Mean rate (±SE) of weight gain decreased from 7.5 ± 1.0 pre to −0.2 ± 1.7 kg/y (p < 0.001) post. In non-ambulatory boys (N = 29), rate of weight gain decreased from 8.3 ± 1.5 pre to −0.6 ± 2.5 kg/y post (p < 0.001). In ambulatory boys (N = 16), rate of weight gain decreased from 6.1 ± 0.7 pre to 1.0 ± 1.3 kg/y post (p < 0.001), and rate of BMI gain decreased from 2.8 ± 0.4 pre to 0.1 ± 0.7 kg/m2/y post (p < 0.001). Metformin reduced weight and BMI in DMD patients on daily GC therapy with excessive weight gain.

My thought is that a drug like that might be more useful for a patient with MD because they have mobility problems. A person with ITP does not and therefore, can exercise or walk the weight off. Also with ITP, patients are not usually on steroids for years at a time whereas an MD patient might be.

I started by asking myself if I would consider it for weight loss, then decided 'no' because that drug might also have side effects. I do have pre-diabetes (Type 2), so if I'd have to use that drug, I'd be happy about the extra perk.

I've been reading about Metformin for years now, and know people who were put on it for pre-diabetes. I've also seen the effects of MD and watched a family member rapidly gain a lot of weight after being put on an antipsychotic med.

As noted in the first article, the benefits were seen "mostly in young adults newly exposed to antipsychotic drugs." The weight gain and related changes in people on antipsychotics is rather dramatic, enough that one of these meds (olanzepine) has at times been used to encourage weight gain in refractory anorexics.

The second article addresses Duchene MD, which is found in male children. As a result, it may be inappropriate to generalize to adults of both genders. People with MD undergo irreversible muscle loss, which has all manner of metabolic effects. Then add in the metabolic effects of long-term steroids, and the picture is quite uncertain.

Here are a couple of articles on metformin in autoimmune disorders:

"Different Effects of Metformin on the Hypothalamic-Pituitary-Thyroid Axis in Bromocriptine- and Cabergoline-treated Patients with Hashimoto's Thyroiditis and Glucose Metabolism Abnormalities."
www.ncbi.nlm.nih.gov/pubmed/26372847

Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis.
www.ncbi.nlm.nih.gov/pubmed/25214721

It seems that more research is needed to sort out what if any benefits there may be.

Sandi,

One more extra perk from metformin. In a newly published article from UAB, and other articles I have seen, metformin may have a beneficial effect on SLE

www.uab.edu/medicine/rheumatology/images/LH_-_Wang_et_al_2015.pdf
NETs mitochondrial DNA and its autoantibody in Systemic Lupus Erythematosus and a proof-of-concept trial of metformin

Also:

www.jimmunol.org/content/192/1_Supplement/200.18.short
Metabolic inhibitors normalize CD4 T cell metabolism and functions, and reverse disease in a murine model of lupus (THER5P.839)
To normalize T cell metabolism in B6.TC mice, we used metformin, which activates the AMPK pathway and inhibits mitochondrial oxygen consumption, and 2-DG, an inhibitor of glycolysis. In vitro, metformin blocks IFNγ production by CD4 T cells and facilitates Treg development. 2-DG also blocks IFNγ production, but only after T cell activation. In vivo, a combined treatment with metformin and 2-DG of B6.TC mice normalized T cell metabolism and reversed disease phenotypes, including T cell activation and autoantibody production. Further, CD4 T cells from SLE patients have an enhanced metabolism as compared to healthy controls, and excessive IFNγ production was significantly reduced by metformin. Our research suggests that T cell metabolism is a novel target for SLE treatment.

This second article is to SLE as Aoi's second article is to autoimmune arthritis, as in both articles metformin helps to regulate T cells.

I also am pre-diabetic. Due to medications I take, weight control has been extremely difficult, in spite of being married to a dietitian. I see my doctor tomorrow and will discuss metformin.

One caution, though: metformin may be contraindicated if there is renal impairment.

Rob:

I made a decision a few months ago that I am done taking new meds unless my life is on the line. I have tried so many and all they have done is cause more problems. I'm going to manage on the ones I take now unless something else crops up. I've taken meds that my doctor suggested and she's given me meds that I've suggested. None of them have done any good. I'm so over drugs at this point!

I need to exercise and eat better. (I keep saying that. Need to actually do it.)

Sandi, I understand your decision, and if I had been through all that you have I might make the same choice.

Objectively, though, and more generally, I see a real possibility that metformin could be of benefit to patients with a wide range of autoimmune diseases, by helping relieve side effects of corticosteroids, such as weight gain, hyperglycemia and insulin resistance, and possibly even reducing autoimmunity. These possible benefits cry out for better research.

At minimum, patients using corticosteroids for more than short duration should be checked regularly for weight gain and rising blood glucose. If efforts to change lifestyle prove futile, metformin should be considered, to reduce symptoms and help prevent pre-diabetes from becoming full-blown Type II diabetes.

I'm with Sandi. Also I'm not sure I'd want to take a pill that causes side effects to counteract the side effects of a pill I'm already taking. (at least that's how I'm reading this)

Taking metformin can cause side effects, but so can NOT taking metformin.

What are the side effects of obesity?
--- more than 300,000 additional deaths per year due to cardiovascular diseases and cancer

What are the side effects hyperglycemia?

Cardiovascular disease
Nerve damage (neuropathy)
Kidney damage (nephropathy) or kidney failure
Damage to the blood vessels of the retina (diabetic retinopathy), potentially leading to blindness
Clouding of the normally clear lens of your eye (cataract)
Feet problems caused by damaged nerves or poor blood flow that can lead to serious infections
Bone and joint problems, such as osteoporosis
Skin problems, including bacterial infections, fungal infections and nonhealing wounds
Teeth and gum infections
www.mayoclinic.org/diseases-conditions/hyperglycemia/basics/complications/con-20034795

If taking metformin helps me lose weight and/or lowers my blood glucose to a safer level, I will gladly trade off the risks of side effects.

Rob16 wrote: ...I see a real possibility that metformin could be of benefit to patients with a wide range of autoimmune diseases, by helping relieve side effects of corticosteroids, ...

I was speaking to your mentioning metformin for those taking steroids. It seems now that most are not on steroids for very long, and once off the weight usually [usually] comes down.

There's a big red box warning for metformin - I don't think I would take this med lightly
www.nlm.nih.gov/medlineplus/druginfo/meds/a696005.html

I agree that length of treatment with steroids is a critical factor in balancing the risks.

The black box warning is only for people with specific risk factors and metformin should not be used for people with those risk factors.

I agree: I would not take it lightly.