When I was diagnosed with type 2 diabetes in 1996, there were only three drugs to choose from: sulfonylureas, metformin, or insulin.
The sulfonylureas make your pancreas produce more insulin. They have been used for decades and are relatively cheap, but like insulin, they can make your blood glucose (BG) levels go too low if you take too much or don’t eat enough, and that can make you gain weight. There is also some evidence that they wear out your beta cells (the cells in the pancreas that produce insulin) and may also contribute to cardiovascular disease.
Metformin is thought to keep the liver from producing too much glucose when it’s not needed, and it is not apt to make your BG levels go too low, although this can happen.
Insulin, of course, is the hormone we don’t produce enough of to cover the insulin resistance that is the hallmark of type 2 diabetes.
Today there are so many drugs for diabetes that it’s difficult to keep track. And as more and more people take these new drugs, more and more potential side effects are being discovered.
Alpha-glucosidase inhibitors like acarbose (Precose) and miglitol (Glyset) slow down starch digestion. The “glitazones” like pioglitazone (Actos) seem to reduce insulin resistance.
The glucagon-like peptide 1 (GLP-1) mimetics like exenatide-1 (Byetta) and several long-acting versions of this injected drug slow down digestion and inhibit the production of glucagon, the hormone that opposes the action of insulin.
GLP-1 is quickly broken down by an enzyme called DPP-4, and drugs that inhibit this enzyme, called “gliptins,” have been developed. The first such drug was sitagliptin (Januvia).
The SGLT-2 inhibitors make you excrete more glucose in the urine, thus reducing the amount of glucose in the blood and wasting a few calories so some people lose a little weight when they take them. Their names end in “gliflozin,” and the first on the market was canagliflozin (Invokana).
Other less-commonly used diabetes drugs include the bile-acid sequestrant colesevelam (Welchol) and bromocriptine (Cycloset).
All these drugs have been approved by the Food and Drug Administration (FDA). Others were initially approved and later removed from the market when unacceptable side effects were reported.
Recently, two reports of potential side effects of SGLT-2 inhibitors and two DPP-4 inhibitors and have been reported.
In April, an FDA advisory committee recommended adding warnings to the labels of DPP-4 inhibitors saxagliptin (Onglyza) and alogliptin (Nesina). The warnings were that these drugs might contribute to heart failure. Note that this is an advisory committee, and the FDA is not required to act on their recommendation. A majority of the committee did not consider the risk high enough to remove the drugs from the market.
Also keep in mind that the reason there may be warnings on these two drugs and not on other gliptins is because the postmarketing trials were completed for these drugs and not for the others. In 2008, the FDA mandated that all new diabetes drugs be tested for cardiovascular safety, and a study of sitagliptin is expected to be reported in June.
Then on Friday, March 15, the FDA warned that the SGLT-2 inhibitors could cause diabetic ketoacidosis (DKA) in people with type 2 diabetes.
DKA is a condition usually found only in people with type 1 diabetes. It happens when insulin levels are very low so the body can’t take up glucose for energy and relies on fatty acids instead. Some of the fatty acids break down into ketone bodies, which are acidic, and it’s too much acidity, the acidosis, that is dangerous.
Even a little insulin will keep the levels of ketone from getting dangerously high, and most people with type 2 diabetes are producing enough insulin to accomplish this. So it is not yet clear why the SGLT-2 drugs can contribute to DKA.
Metformin has also been associated with acidosis, in this case, lactic acidosis, or too much lactic acid in the blood. However, the incidence of this condition is low.
In both cases, people who get acidosis tend to have other medical conditions including infection, dehydration, renal dysfunction, liver disease, or heavy alcohol ingestion.
So what does all this mean for you? Should you avoid all oral diabetes drugs because of possible side effects and let your BG levels get high, or use insulin alone? I think no to both questions.
Remember, we know that high BG levels cause serious complications like blindness, amputations, and kidney failure. And different people have different reactions to oral drugs. A drug that might cause acidosis in one person could cause nothing in you except lower BG levels.
The important thing is to keep in mind that all drugs may have side effects, to have some sense of what those side effects are, and to be vigilant to any symptoms that something is wrong. For example, if you start a new drug and find yourself breathless when you didn’t use to be, call your doctor for advice. Symptoms of acidosis include difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness.
Side effects sometimes show up only after a large number of people have taken them. So as long as an older drug works for you, it’s often a better bet. Newer drugs not only have more unknowns, but they’re usually a lot more expensive. They may eventually turn out to be wonderful, and with time they’ll become generic. If you can, wait until more is known about them.
More interesting articles on medications:
Metformin and Glucagon
Bromocriptine: A New Type of Type 2 Drug
Actos Goes Generic
What Can We Believe?
Weight Gain and Drugs
Warning Labels for Diabetes Drug Side Effects (humor)