Research suggests diabetes drug acts differently from previous theories

May 5, 2016, Mayo Clinic
Metformin 500mg tablets. Credit: public domain

A Mayo Clinic study suggests laboratory findings do not tell the whole story of how the diabetes drug metformin works to limit the level of glucose in the blood. The researchers found that metformin does not limit the action of the hormone glucagon, specifically glucagon-stimulated glucose production from the liver. The article appears in the journal Cell Reports.

"In our clinical trial, metformin treatment appeared to trigger a compensatory increase of glucagon that may mitigate the ability of metformin to lower glucose production in prediabetic individuals and prevent the likelihood of hypoglycemia," explained K. Sreekumaran Nair, M.D., Ph.D., Mayo Clinic endocrinologist and senior author of the article.

Metformin's action is generally related to the release of glucose from the liver. The liver releases glucose when prodded by a pancreatic hormone called glucagon. Glucagon is released when drop. Metformin is thought to limit the action of glucagon, the substances used to make it, or affect the level of enzymes used to make it.

Yet that's not what Dr. Nair and colleagues found in their double-blind study of nine prediabetic individuals.

The researchers found that for the six individuals with fasting (basal) glucagon levels of less than 150 picograms/milliliter, metformin treatment decreased the liver's production of glucose as expected. But for the three individuals with basal levels greater than 150 pg/mL, levels of produced by the actually increased after metformin treatment.

This contradictory finding may be due to both the study design and participants. Unlike previous preclinical metformin research, this study used human participants and metformin at therapeutic doses. Studies in animal or cellular models have examined higher doses, or used drugs in the same class as that are not approved for use in humans. Also, unlike many other human studies based on participants with type 2 diabetes, the current report is based on prediabetic individuals.

More research on a larger and more diverse group of patients is needed before the findings can be widely applied.

Explore further: Study: Most-used diabetes drug works in different way than previously thought

Related Stories

Study: Most-used diabetes drug works in different way than previously thought

January 6, 2013
A team, led by senior author Morris J. Birnbaum, MD, PhD, the Willard and Rhoda Ware Professor of Medicine, with the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, ...

Study finds exercise can help enhance diabetic medication

April 6, 2016
Exercise can help enhance the effects of blood glucose-lowering medication, according to an award-winning study by a University of Georgia graduate student.

Study reverses current thought on treatment of cirrhosis

June 19, 2014
Researchers at Mayo Clinic released a new study reversing current thought on the treatment of cirrhotic patients with type 2 diabetes. The study found that the continuation of metformin after a cirrhosis diagnosis improved ...

Common diabetes drug associated with risk of low levels of thyroid hormone

September 22, 2014
Metformin, a commonly used drug for treating type 2 diabetes, is linked to an increased risk of low thyroid-stimulating hormone (TSH) levels in patients with underactive thyroids (hypothyroidism), according to a study in ...

Diabetes drug metformin's primary effect is in the gut, not the bloodstream

August 18, 2015
Although metformin was introduced as a treatment for type 2 diabetes nearly 60 years ago and is now the recommended first-line treatment for newly diagnosed patients, researchers still debate precisely how the drug works. ...

Review suggests metformin associated with small height increase in children

September 28, 2015
A review of the medical literature suggests the diabetes medication metformin may be associated with a small increase in height in children and adolescents in randomized clinical trials providing the largest cumulative metformin ...

Recommended for you

Genetic discovery may help better identify children at risk for type 1 diabetes

January 17, 2018
Six novel chromosomal regions identified by scientists leading a large, prospective study of children at risk for type 1 diabetes will enable the discovery of more genes that cause the disease and more targets for treating ...

Thirty-year study shows women who breastfeed for six months or more reduce their diabetes risk

January 16, 2018
In a long-term national study, breastfeeding for six months or longer cuts the risk of developing type 2 diabetes nearly in half for women throughout their childbearing years, according to new Kaiser Permanente research published ...

Women who have gestational diabetes in pregnancy are at higher risk of future health issues

January 16, 2018
Women who have gestational diabetes mellitus (GDM) during pregnancy have a higher than usual risk of developing type 2 diabetes, hypertension, and ischemic heart disease in the future, according to new research led by the ...

Diabetes gene found that causes low and high blood sugar levels in the same family

January 15, 2018
A study of families with rare blood sugar conditions has revealed a new gene thought to be critical in the regulation of insulin, the key hormone in diabetes.

Discovery could lead to new therapies for diabetics

January 12, 2018
New research by MDI Biological Laboratory scientist Sandra Rieger, Ph.D., and her team has demonstrated that an enzyme she had previously identified as playing a role in peripheral neuropathy induced by cancer chemotherapy ...

Enzyme shown to regulate inflammation and metabolism in fat tissue

January 11, 2018
The human body has two primary kinds of fat—white fat, which stores excess calories and is associated with obesity, and brown fat, which burns calories in order to produce heat and has garnered interest as a potential means ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.