June 1st, 2015

What Metformin Does to Wildlife

What Metformin Does to Wildlife

Here is an article that just shows how innocent an effort to improve patient health and well being can tip the scales on the other end of the balance.  Although there are many issues that play into prescribing the use of Metformin for type 2 diabetes consistent with renal clearance, GI disorders and drug sensitivity what is it doing for us or our environment later on down the road.  I talk about it often but here is a good example to back me up on being very cautious in prescribing drugs new and old for our older patients. The alarming part of this study shows how a unfamiliar chemical compound introduced to our normal natural chemistry and seriously and permanently alter our genomes (DNA) that would effect  future natural development of the human race.  Is this good or bad, think about it, not just metformin but many others guilty of this malformation.

May 12, 2015

Researchers from the University of Wisconsin have found that exposing male fish to metformin found in wastewater effluent causes the development of intersex gonads.  Male fish exposed to the widely used type 2 diabetes medication were also smaller in size and less fertile than fish that were not exposed.

Intersex fish have been detected in freshwater systems throughout the world.  Some studies have suggested that hormones from birth control medications discovered in wastewater treatment plant effluent are the probable culprits.  Other research, however, has indicated that this endocrine disruption is not necessarily solely caused by hormone receptor interactions.

Related: Is Metformin Underutilized?
Senior author Dr. Rebecca Klaper, associate professor and director, Great Lake Genomics Center, School of Freshwater Sciences, University of Wisconsin-Milwaukee, and colleagues discovered that metformin, a nonhormone medication and one of the most common pharmaceuticals found in effluent, was a potential endocrine disruptor among adult fish in an earlier study.

For their current study, Dr. Klaper and co-author Nicholas Niemuth, research specialist at the School of Freshwater Sciences, sought to examine metformin’s impact on developing fish.

Related: "Remarkable" Effect of Metformin
“We wanted to determine if metformin had any impact on fish health as we (and others now) are finding it in the environment at higher levels than other emerging contaminants,” Dr. Klaper said.

“This study is the first to indicate that this drug taken for type 2 diabetes as well as a few other conditions has the potential to be an endocrine disruptor and impact development,” she continued.

The authors examined the effects of a continuous metformin exposure on fathead minnows from birth to adulthood.  The concentration of metformin was similar to that found in wastewater effluent.

They found a significant occurrence of intersexuality among male fish exposed to metformin (average score, 0.2 for control males vs. 3.8 for treated males).  Further, 84% of metformin-exposed male fish were intersexed per treatment, compared with only 13% of controls.

Significant differences in weight and condition factor were also reported among metformin-treated male fish—but not female fish.

Researchers also discovered that metformin-exposed pairs laid significantly fewer and smaller clutches than control fish. They noted in the study that treated pairs consisting of male intersex fish still produced eggs.

“We were very surprised by the results as this medication is designed to impact metabolism and insulin, not impact reproduction,” said Dr. Klaper. “It does not look like a hormone or a compound that would be related to endocrine function or sexual development.”

She pointed out that, although it is too early to tell what the implications may be for human intake of metformin, “it does indicate that more research should be done on the potential impacts of this medication on development,” she said.

She added that it does not mean that adults taking metformin will develop endocrine problems.

In terms of future research, Dr. Klaper said that they are trying to determine the mechanism “by which the medication may have its impact” and “the minimum dose where we see these effects.”

The ultimate take-home message of the study, according to Dr. Klaper, is that this research “is just the first step in determining the potential health concerns for this medication, but overall prescription of medications should not be taken lightly as they may have bigger impacts over their life cycle than what is intended.”

This study was published in Chemosphere.

 -Meredith Edwards White

References:

1. Niemuth NJ, Klaper RD. Emerging wastewater contaminant metformin causes intersex and reduced fecundity in fish. Chemosphere. 2015;135:38-45.

2. Niemuth NJ, Jordan R, Crago J, Blanksma C, Johnson R, Klaper RD. Metformin exposure at environmentally relevant concentrations causes potential endocrine disruption in adult male fish. Environ Toxicol Chem. 2015;34(2):291-296.