Pharmaceutical Lagniappe

Metformin: A Drug Examined

Would your ears perk up if you heard your neighborhood drugstore stocks a pill that decreases appetite, lowers cancer rates, prevents diabetes, staves off Parkinson’s disease and decreases wrinkles? Moreover, it’s a cheap generic with minimal adverse effects prescribed in one form or another since the Middle Ages.

If you know anyone with adult-onset type 2 diabetes, you probably know someone already taking this wonder drug. If you yourself have diabetes, you’re likely taking it yourself. The drug is metformin, trade name Glucophage. It works on many fronts – decreases intestinal absorption and liver production of glucose, decreases insulin resistance and sends a message to the brain to eat less.

“Probably 95 percent of my type 2 diabetics with normal renal function take metformin,” says Dr. Samuel Andrews, an internist with a subspecialty in endocrinology who currently practices at Ochsner Medical Center in Jefferson Parish. “It can cause often transient nausea and diarrhea, but in general metformin is very well tolerated.”

Besides being the first choice drug to treat most type 2 diabetes, metformin can delay its onset, another indication for metformin that deserves more attention, according to Dr. Andrews and Dr. April Fox, an internist and kidney specialist. Taking a medication used to treat a specific disease to prevent that disease is often a hard sell. But recent data are clear: persons with slightly elevated blood glucose levels can delay and sometimes abort the onset of definitive diabetes, especially if they’re overweight.

“And I prescribe it for women with polycystic ovary syndrome,” says Dr. Andrews referring to the most common endocrine disorder in women of childbearing age. Associated symptoms often include obesity, decreased periods, acne, infertility and increased facial hair.

What about cancer? Just having diabetes increases the risk of cancer. Certain cancer cells grow faster and more aggressive in the presence of elevated blood glucose. Metformin taken by diabetic patients significantly reduces pancreatic, breast and colon cancer risks.

And when cancers do occur, metformin can still help. It stimulates some cancer cells in a way that makes therapy more effective. Diabetic patients with advanced lung cancers taking metformin respond better to radiation therapy than those who don’t take the drug. For all men, beginning metformin before surgery for prostate cancer seems to reduce reoccurrences.
Diabetics are twofold more likely to develop Parkinson’s disease than those without diabetes. When metformin is in the treatment mixture, this increased risk for Parkinson’s disease seems to go away.

What about metformin and heart disease? The data are murkier. Any boost to weight loss and glucose control should decrease cardiovascular diseases. Earlier studies with diabetics showed anywhere from 15 to 25 percent reduction in the risk of coronary artery disease. But more recent studies are showing no improvement in cardiovascular endpoints for non-diabetics who take metformin.

So where did this wonder medicine originate? Medieval herbalists used an extract from the leaves of a shrub native to the Middle East to treat excessive urination, a symptom of uncontrolled diabetes A college agricultural professor, apparently unaware the common name for Galega officinalis was goat’s rue in Europe, imported this plant into the United States to test as a forage crop in the 1890s. It was too toxic for grazing cattle, sheep and horses. It escaped from its Utah test fields and is now an invasive weed. Angry farmers took to calling it “professor weed” while others refer to it as “French lilac” or “Italian fitch.”

European chemists in the 1920s first isolated and synthesized metformin from goat’s rue. Their findings fell by the wayside as diabetic research shifted to insulin. Then a French physician renamed the drug Glucophage, meaning “glucose eater” and began treating diabetics with it in the ’50s. European drug regulators quickly approved metformin, noting that it was an oral drug that didn’t cause hypoglycemic reactions. Diabetics in England started taking it in ’58, but it took almost three decades before any drug company in the United States expressed interest. Since FDA approval in ’95, metformin has become initial drug of choice for type 2 diabetes when diet and exercise fail.

But wouldn’t it be nice if metformin slowed aging and increased longevity? It does according to a researcher in Belgium; he says that not only did metformin extend life, it decreased wrinkles. Unfortunately these metformin benefits are not ready for prime time. The study subjects were small, round worms. But you can see pictures showing treated worms with less wrinkles (pnas.org/content/111/24/E2501/F5.expansion.html).

One final question for Dr. Andrews: How does metformin compare to Sugar Busters? “Metformin is right up there with Sugar Busters, but Sugar Busters is better for weight loss,” says Dr. Andrews, one of the authors of the diet book that took New Orleans by a storm before becoming a national best seller in 1991.

Lagniappe Medicines
Metformin is an addition to a select group of drugs with benefits that transcend a single organ system. I call them “lagniappe drugs.” They deserve sainthood, as each is known for two or more miraculous therapeutic benefits crossing over into multiple disease categories. Aspirin, doxycycline and statins are members of this saintly group.

Aspirin is the prototype of the lagniappe drugs. Hippocrates treated pain and fevers with an extract of willow tree bark. Aspirin remains the go-to drug for minor aches and pains, headaches and fever in adults. Aspirin has not only endured, new benefits have emerged. Taken daily on a long-term basis, low dose aspirin decreases the incidence of strokes, heart attacks, blood vessel clots and colon cancers.

Doxycycline is a semisynthetic tetracycline. Physicians prescribe it for a wide spectrum of infections from anthrax to syphilis. Dr. George Pankey at Ochsner was the first physician I remember who talked about anti-inflammatory properties of doxycycline separate and apart from its antibacterial activity. And indeed today doxycycline is used to help decrease inflammation in a host of common problems including rheumatoid arthritis, chronic bronchitis, acne and rosacea.

The youngest proposed members of this saintly club are the statins. Lipitor, Zocor, Pravachol and others are all therapeutic cousins that decrease cholesterol and reduce heart attacks. But by our definition there must be therapeutic benefit in at least one other bodily system. There were high hopes that statins would decrease reduce strokes, heal traumatic brain injuries and slow the progression of Alzheimer’s disease. So far, there are no strong data supporting these claims. Just recently a scientist suggested that statins might help persons infected with Ebola. Now that would get the statins out of the pledge class into the saintly club without a black ball.