REtrospective #245: “…in patients on sulfonylureas”

Lots of Type 2 diabetes patients are on sulfonylureas (SUs). They were the first class of oral anti-diabetic medications approved in the U.S. (1955) and remained the only class until 1995 when metformin (Glucophage) was added. Metformin eventually took over and became the first-line drug, used even for the treatment of Prediabetes. 

Second generation SUs, approved in 1984, include the familiar generics glyburide (Micronase, Diabeta) and glipizide (Glucotrol). All SUs act by increasing insulin release from the beta cells in the pancreas. Some diabetes experts feel that SUs accelerate the loss of beta cells from the pancreas and should be avoided. Ralph DeFronzo, MD, in his 2008 ADA Banting Award keynote speech, said, “Sulfonylureas are not recommended because, after an initial improvement in glycemic control, they are associated with a progressive rise in A1c and progressive loss of ß-cell function”

The Wikipedia entry advises that SUs “decrease lipolysis [breakdown and release of fatty acids by adipose tissue] and decrease clearance of insulin by the liver.” Thus, “like insulin, sulfonylureas can induce weight gain…”). In addition, “All sulfonylureas carry an FDA-required warning about increased risk of cardiovascular death.” And that’s not all.

Wikipedia continues, “First line therapy with sulfonylureas significantly increases the risk for death in patients with Type 2 diabetes when compared with treatment with metformin. Additional research showed that the combination of metformin and a sulfonylurea was also associated with a significantly increased risk for death when compared with combination therapy with metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor

“Sulfonylureas are potentially teratogenic [think 2-headed] and cannot be used in pregnancy or in patients who may become pregnant. Impairment of liver or kidney function increases risk of hypoglycemia, and are contraindications.”

And then there are the Interactions. Wikipedia: “Drugs that potentiate or prolong the effects of sulfonylureas and therefore increase the risk of hypoglycemia include acetylsalicylic acid [aspirin] and derivatives, allopurinol, sulfonamides, and fibrates. Drugs that worsen glucose tolerance, contravening the effects of anti-diabetics, include corticosteroids, isoniazide, oral contraceptives and other estrogens, sympathomimetics, and thyroid hormones. Sulfonylureas tend to interact with a wide variety of other drugs, but these interactions, as well as their clinical significance, vary from substance to substance.” Sympathomimetics include caffeine and some decongestants.

Then there’s a 2014 report in JAMA Internal Medicine regarding interactions of sulfonylureas and antibiotics resulting in hospitalizations or emergency department visits. The lede: “Use of certain antimicrobial agents is linked to an increased risk of hypoglycemia in older patients on sulfonylureas, according to a study of Medicare claims.” The JAMA finding: “Physicians should definitely avoid using those antibiotics in patients on sulfonylureas.”

I was on a sulfonylurea (Micronase, then the generic glyburide) from my initial T2 diagnosis in 1986. When Glucophage (metformin) was permitted in the U.S., my doctor added it. As I continued to eat “one-size-fits-all” balanced diet, with 55% to 60% carbohydrates as recommended since 1980 for everyone by the USDA’s Dietary Guidelines for Americans, my diabetes got progressively worse. Eventually, I was “maxed out” on both metformin and glyburide and starting a 3^rd class of oral antidiabetic drugs. I knew that my drug “cocktail” was soon destined to be replaced by injected insulin.

That’s when my doctor, who had just read Gary Taubes’s “What If It’s All Been a Big Fat Lie,” the NYT Magazine cover story on July 7, 2002, suggested I try a Very Low Carb diet to lost weight. I did and the first day I got hypoglycemia. I ate a candy bar and called the doc. He told me to drop the new drug he had added.” The second day, hypoglycemia returned and he told me to cut the glyburide and metformin in half. I did, and the next day, he said, “Cut them in half again.” Eventually I stopped the glyburide and for the last 17 years, I have taken just one 500mg of metformin a day.

Doctors still prescribe SUs. They’re dirt cheap and they lower blood sugar and A1c’s (which are elevated because of the foods we eat). But metformin is now dirt cheap too. So, for patients still on sulfonylureas, I ask myself, in view of all the downside risks, why don’t they just change the foods they eat? They won’t need to take a sulfonylurea.