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Diabetic Medications and Exercise, Part 1: Oral Medications

May 11, 2009

Sheri Colberg, Ph.D., FACSM, has been helping patients with diabetes successfully increase physical activity for many years and has written numerous books that patients and clinicians use. Most of her work recently has been about insulin and exercise, but many of you have written me to ask, “What about oral medications?” This week Dr. Colberg begins explaining oral medications in Diabetic Medications and Exercise, Part 1: Oral Medications.

Diabetic Medications and Exercise, Part 1: Oral Medications


By Sheri Colberg, Ph.D., FACSM

If you use any of the oral diabetes medications, knowing their potential glucose-lowering effects is important. In general, oral medications for diabetes target one or more of three metabolic disorders found in diabetes; decreased insulin production by the beta cells of the pancreas, elevations in the  production of glucose by the liver, or increased insulin resistance in muscle and fat tissues. Their many classes, differing actions, and names are listed in table 3.3. If you ever experience a change in your exercise routine, you may need to consult with your doctor about adjusting the doses of oral medications that you take, particularly if you begin to engage regularly in more physical activity than you did before.

SheriKey Point: An increase in your activity level may require you to lower your doses, even of oral diabetes medications that do not usually cause exercise-related low blood sugars.


A class of drugs called sulfonylureas was the only one available to treat Type 2 diabetes for many years. They work by stimulating insulin release from the pancreas and decreasing insulin resistance. The only first-generation one still on the market is Diabinese (generic name: chloropropamide), which can last for up to 72 hours. Its long duration gives it a greater chance of causing hypoglycemia during or after exercise, especially if you have kidney problems. The more commonly used, second-generation sulfonylureas are more effective at smaller doses and include Amaryl, Glucotrol, DiaBeta, Micronase, and Glynase. Of these, only the latter three (all brand names for generic glyburide) carry a greater risk of causing exercise lows because of their action (24 hours versus only 12 to 16 for Amaryl and Glucotrol), although all of them often contribute to weight gain.

In general, oral agents with the longest duration, such as Diabinese, DiaBeta, Micronase, and Glynase have the greatest potential to cause hypoglycemia during and following exercise, especially when you do any unusual or prolonged activity.


Metformin (marketed both in its generic form and as brands like Glucophage) is in a separate class of drugs called biguanides. Its most important action is to reduce the liver’s output of glucose (often elevated in the early morning in people with diabetes), but it has other actions including lowering glucose absorption from the gut and enhancing insulin action. Metformin is, by far, the most prescribed of all oral diabetes drugs. One of its main advantages is that, unlike sulfonylureas, it doesn’t contribute to weight gain; it’s also unlikely to cause hypoglycemia and can be used in combination with other medications. A recent study investigated using metformin in overweight adults with Type 1 diabetes, even though this drug is normally prescribed only to treat Type 2. Although not given to normal-weight Type 1s, it may prove to be a useful therapy for overweight people with Type 1 diabetes who have impaired insulin action that is common to Type 2 diabetes (but, of course, regular exercise would also help their insulin action).

TZDs (Glitazones)

Another class of drugs called thiazolidinediones, or TZDs or glitazones for short (including Avandia and Actos), directly enhance peripheral insulin sensitivity without affecting insulin secretion from the pancreas. Although these drugs don’t usually cause low blood sugars, Avandia recently received a lot of bad publicity because of its potential to worsen a weakened heart (heart failure). As a result, both medications in this class now have to carry a “black box” warning on them, and many people have chosen to stop taking Avandia or combination drugs containing it like Avandamet and Avandaryl. But their ability to increase insulin action much like exercise does makes them an attractive treatment for those with Type 2 diabetes..

Alpha-Glucosidase Inhibitors

Alpha-glucosidase inhibitors, marketed as Precose and Glyset, can prevent increases in blood sugar following meals by delaying carbohydrate digestion in the small intestine. Taking these medications directly before exercise if you eat extra carbohydrate during the activity would slow your absorption of them as well, and they can cause undesirable side effects like flatulence and diarrhea. Keep in mind that exercise itself usually slows the digestion of foods, so if you are exercising after eating you may need lower or no doses of these medications

DPP-4 Inhibitors

Some new classes of meds for people with Type 2 diabetes are also being created that target insulin release and insulin action, including Januvia (now approved by the FDA) and Galvus, both of which work with gut hormones, natural enzymes, and the body’s own insulin to control blood glucose levels. This class of oral meds works by inhibiting DPP-4, an enzyme that breaks down glucagon-like peptide-1 (GLP-1). Delayed GLP-1 degradation extends the action of insulin while suppressing glucagon release. Several other potential classes are also under investigation by pharmaceutical companies.

Combination Therapies

If a single medication does not adequately control your blood sugars, your doctor may put you on a combination therapy that requires you to take two or more different drugs. Often, you can now get combination drugs that have two of these classes of drugs together, such as Avandia and Amaryl to form Avandaryl, or glyburide and metformin as Glucovance. These combination drugs make taking multiple drugs easier. Such combinations, however, can make the prediction of an exercise response more difficult if you don’t know which classes of drugs are in them.

If oral medications, alone or in combination, stop effectively controlling your blood sugars, you may have to change to insulin therapy for better control, often starting with just basal insulin at bedtime. Some studies have shown that starting people on insulin sooner may actually better preserve your remaining beta cell function, so this approach is worth considering. Similarly, if you have LADA (Type 1.5 diabetes), its full onset may be delayed enough that taking oral medications may effectively control your blood sugars for a while, but usually you will have to start taking insulin at some point for adequate control.

In Part 2 of this series, we’ll discuss the effects of two of the newer medications, Symlin and Byetta, both of which can increase risk for hypoglycemia during exercise and may need to be adjusted for physical activity.

This column is excerpted from Diabetic Athlete’s Handbook (released November 2008 from Human Kinetics), which contains essential exercise-related information and examples for Type 1 and Type 2 diabetic exercisers. Look for it in stores or find links to places to buy it online at www.shericolberg.com, along with additional information.