Diabetes Drugs: Balancing Side Effects

If some combination of losing weight, making dietary changes and exercising doesn’t help a diabetic achieve target blood sugar levels, a doctor will prescribe oral antidiabetic medications. With the increased prevalence in type 2 diabetes has come a vast increase in the number of drugs designed to manage the condition. Sometimes a single medication is effective. In other cases, a combination of medications works better.

The goal of these oral medications is to help the body stimulate and use insulin more effectively and to lower blood sugar. However, different classes of these drugs achieve this goal differently. Exactly which class of drug your health care practitioner prescribes for you will depend on your individual situation, your blood glucose levels and any side effects you may experience.

Note that eventually most type 2 diabetics who don’t lower their blood sugar levels will stop producing insulin altogether. At this point, diet and exercise will not be able to reverse the effects of diabetes, and many type 2 diabetics will ultimately need insulin therapy (via injection) in combination with oral antidiabetic medications.

The Most Commonly Prescribed Medications for Type 2 Diabetes

Type of Medication: Oral
Class: Meglitinides
Brand Names (FDA Approval Date): Prandin (1997), Starlix (1997)
How They Work: Short-acting drugs; increase insulin production for 4 hours after the onset of high-blood sugar; taken at mealtimes
Pros: Work quickly and don’t stay in the body long (which is why they need to be taken with or just before meals)
Possible Side Effects: Low blood sugar (hypoglycemia), weight gain, nausea, back pain, headache
Drug Interactions: Antifungals (drugs prescribed to combat fungal infections) and some antibiotics (like erythromycin) may result in hypoglycemia. Calcium channel blockers, corticosteroids, diuretics and thyroid drugs may cause hyperglycemia (high blood sugar).

Type of Medication: Oral
Class: Sulfonylureas
Brand Names (FDA Approval Date): Glucotrol (1994), Amaryl (1995)
How They Work: Stimulate the release of insulin
Pros: Inexpensive, very effective at bringing down blood glucose levels
Possible Side Effects: Hypoglycemia, anemia, dizziness, drowsiness, weight gain, nausea, skin rash, headache
Drug Interactions: Androgens, anticoagulants, magnesium, and tricyclic antidepressants can increase the effectiveness of this class of drugs, resulting in hypoglycemia. Calcium channel blockers, estrogens, oral contraceptives, diuretics and thyroid medications can decrease the effectiveness of these drugs.

Type of Medication: Oral
Class: Biguanides
Brand Names (FDA Approval Date): Fortamet (2004), Glucophage (2000), Glumetza (2005), metformin (generic)
How They Work: Inhibit the release of glucose from the liver and improve sensitivity to insulin
Pros: Do not usually cause hypoglycemia
Possible Side Effects: Nausea, diarrhea, harmful buildup of lactic acid (lactic acidosis), metallic taste in mouth, weight loss
Drug Interactions: Some antibiotics (trimethoprim or vancomycin), diuretics (amiloride and furosemide), gastrointestinal medications (cimetidine and ranitidine), and heart medications (digoxin) can react negatively with this class of drug. Negative interactions can range from worsening of side effects to hypoglycemia. Morphine; the antimalaria drug quinine; and warfarin, a blood thinner, should be avoided when using biguanides. Those on biguanides must also limit alcohol consumption.

Type of Medication: Oral
Class: Thiazolidinediones
Brand Names (FDA Approval Date): Avandia (1999), Actos (1999)
How They Work: Increase insulin sensitivity in muscles and the liver
Pros: Don’t put stress on the pancreas to keep producing more and more insulin; are available in combination pills with metformin and sulfonylurea medicines
Possible Side Effects: Heart failure or heart attack (more common in those who take these drugs along with insulin), respiratory problems, stroke, liver disease, bone fractures, fluid retention, abdominal pain, blurred vision, dry mouth, increased urination, rapid weight gain or loss, bleeding or bruising, fatigue. Those taking Actos may increase their risk of bladder cancer.
Drug Interactions: Some high-blood pressure meds (bosentan) when used with this class of drug can increase the risk of liver damage. Beta blockers are also contraindicated because of the risk of low blood sugar. Thiazolidinediones may decrease the effectiveness and increase the side effects of ibuprofen and anticoagulants like warfarin. Also those with acute respiratory problems such as asthma or COPD should not take these types of diabetes drugs.

Type of Medication: Oral
Class: SGLT2 inhibitors
Brand Names (FDA Approval Date): Invokana (2013), Forxiga (2014), Jardiance (2014)
How They Work: hese medications, which have been FDA-approved since 2013, lower blood sugar by causing the kidneys to remove sugar from the body through urine. SGLT2 inhibitors are available as a single-ingredient product (oral drug) and also in combination with other diabetes medications like Metformin. The drugs are FDA-approved for use with type 2 diabetes patients only and their safety hasn’t been established for type 1 diabetics.
Pros: Some studies show an increase in HDL or “good” cholesterol levels (though similar increase in “bad” cholesterol, or LDL, may counter this benefit). Reduction in blood pressure, body weight, and body mass also occurs for many patients on this medication.

Research released the spring of 2015 by the FDA warns that these medications may lead to ketoacidosis, a serious condition in which the body produces high levels of blood acids called ketones. These complications typically result in hospitalization and the FDA is continuing to investigate whether more severe warnings are needed. Symptoms of ketoacidosis include difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness. In the FDA’s review of their Adverse Event Reporting System Database the agency identified 20 cases of acidosis that were linked to patients who were taking SGLT2 inhibitors from March 2013 to June 2014.

Additional side effects include hypotension (low blood pressure) which can result in fainting or dizziness in some patients and may pose a risk for those with heart conditions; risk of urinary tract infections, bladder infections, and yeast infections; and some research shows a higher risk of bladder cancer in those who have used these drugs. These medications are not recommended for those with kidney disease.

Contraindications: These drugs are not FDA-approved for type 1 diabetes and the risk/benefit of prescribing to pregnant women, nursing mothers, and the elderly must be carefully considered. Those with diabetic ketoacidosis should not take these drugs.

Type of Medication: Injectable Medications
Class: Amylin Mimetics
Brand Names (FDA Approval Date): Symlin (2007), SymlinPen
How They Work: Slow down the movement of food through the stomach and help prevent the liver from releasing stored glucose into the blood
Pros: May suppress hunger and promote weight loss
Possible Side Effects: Hypoglycemia, nausea or vomiting, headache, redness and irritation at injection site

Drug Interactions: Those taking drugs (such as astropine) for gastrointestinal issues should not take this class of drugs as side effects can worsen. Those on oral antidiabetic drugs, ACE inhibitors and some antibiotics should speak with their health care practitioner about increased susceptibility to hypoglycemia when using these drugs together.

Type of Medication: Injectable Medications
Class: Incretin Mimetics
Brand Names (FDA Approval Date): Bydureon (2012), Byetta (2005), Victoza (2010)
How They Work: Stimulate the release of insulin; commonly used with oral antidiabetic drugs such as metformin and sulfonylurea meds
Pros: May promote modest weight loss
Possible Side Effects: Nausea or vomiting, headache, dizziness, kidney damage or failure (in rare cases), thyroid tumors (in animal studies). Experts recommend that you do not use these drugs if you have a personal or family history of thyroid cancer.
Drug Interactions: You may be more likely to develop hypoglycemia if you use these drugs with oral antidiabetic medications that can lower blood sugar. Discuss using incretin mimetics with your doctor if you take glyburides, glipizides, or other antidiabetic drugs as they can reduce their effectiveness. This class of drugs can also make it more difficult to absorb medications that are given orally like lithium, certain seizure medications, or medications that lower blood pressure such as digoxin.

Geri Anne Fennessey

Geri Anne Fennessey

Geri Anne Fennessey is a New York City-based freelance writer and communications consultant.

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