Type 2 Diabetes Drugs Linked to Higher Cardiovascular Risk

Patient Expert
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It’s a common issue for the 29 million-plus Americans with type 2 diabetes. You are taking metformin (Glucophage), but you can’t tolerate the side effects. Or, your blood sugar levels are still too high. Your doctor adds a “second-line” drug, usually a sulfonylurea drug or insulin. Around 60 percent of patients with type 2 diabetes take one of these two drugs. Now, researchers report that these drugs greatly increase your risk of cardiovascular disease compared to other drugs.

If you find yourself in this situation, here’s what you need to know.

About cardiovascular disease

Cardiovascular disease includes a number of serious conditions, including:

  • Coronary artery disease
  • High blood pressure
  • Heart attack
  • Congestive heart failure
  • Abnormal heart rhythms
  • Stroke
  • Peripheral artery disease, leading to amputations

Cardiovascular disease is the leading cause of added illness and death in people with type 2 diabetes. Reducing this risk, therefore, needs to be part of your type 2 diabetes treatment.

Diabetes drug risks

Research published in the Journal of the American Medical Association (JAMA) was concerning. Compared to newer drugs for type 2 diabetes, sulfonylurea drugs and insulin greatly increased the risk of cardiovascular disease.

Sulfonylureas increased the risk by 36 percent. Sulfonylurea drugs include:

  • Glyburide (Diabeta, Glynase, Micronase)
  • Micronized glyburide (Glynase Prestabs)
  • Glipizide (Glucotrol)
  • Glipizide extended-release (Glucotrol Xl)
  • Glimepiride (Amaryl)
  • Gliclazide (Diamicron)
  • Chlorpropamide (Diabinese)
  • Tolazamide (Tolinase)
  • Tolbutamide (Orinase, Tol-Tab)

Sulfonylurea drugs are also associated with other health concerns.

Basal insulin increased the risk by 50 percent. Basal insulin, sometimes called background insulin, is intermediate- or long-acting insulin, and includes:

  • Neutral protamine Hagedorn (NPH)
  • Detemir (Levemir)
  • Glargine (Lantus, Tougeo, Basaglar)
  • Degludec (Tresiba)

What are your options?

If you have type 2 diabetes and are taking a sulfonylurea drug or insulin, what are your options?

The researchers recommend that after metformin, doctors avoid prescribing sulfonylurea drugs and insulin, and instead, prescribe newer medications such as:

  • Glucagon-like peptide-1 (GLP-1) receptor agonists
  • Sodium-glucose cotransporter 2 (SGLT-2) inhibitors
  • Dipeptidyl peptidase 4 (DPP-4) inhibitors

These are the generic and brand names of the key drugs in these three categories:

Glucagon-like peptide-1 (GLP-1) receptor agonists

  • Dulaglutide (Trulicity)
  • Exenatide (Byetta)
  • Exenatide Extended Release (Bydureon, Bydureon, BCise)
  • Liraglutide (Victoza, Saxenda)
  • Semaglutide (Ozempic)

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors

  • Canagliflozin (Invokana)
  • Dapagliflozin (Farxiga)
  • Empagliflozin (Jardiance)
  • Empagliflozin/linagliptin (Glyxambi)
  • Empagliflozin/metformin (Synjardy)
  • Dapagliflozin/metformin (Xigduo XR)

Dipeptidyl peptidase 4 (DPP-4) inhibitors

  • Saxagliptin (Onglyza)
  • Sitagliptin (Januvia)
  • Alogliptin (Nesina)
  • Linagliptin (Tradjenta)

These drugs are not linked to an increased risk of cardiovascular problems. They are, however, much more expensive than sulfonylureas.

According to Drugs.com, a GLP-1 agonist drug like dulaglutide (Trulicity) currently retails for more than $700 per month. A SGLT-2 inhibitor Canagliflozin (Invokana) retails for around $500 per month. Even with insurance or Medicare, co-pays for these drugs can also be high.

In contrast, retail costs for glyburide are around $18 per month, and around $55 per month for tolazamide. Retail costs for basal insulin range from around $25 per vial (Walmart/Sam’s Club ReliOn brand NPH) up to around $500 per month for newer drugs like glargine and degludec.

The prohibitive cost is the primary reason doctors are less likely to prescribe the newer drugs.

Your next steps

If you have type 2 diabetes and are taking sulfonylureas or insulin, your first step is to talk with your doctor to explore your options. You should also find out the costs and co-pays involved with making a switch to one of the newer drugs. Together, based on the health implications and costs, you and your physician can decide on your next steps.

Going forward

This situation makes one thing clear: Type 2 diabetes patients need a major change in the standard approach to treatment, not to mention the costs associated with those treatments. Specifically, how physicians prescribe type 2 diabetes drugs needs to better reflect the risks associated with the older drugs.

As the JAMA study's lead author, Dr. Matthew O'Brien of Northwestern University said: "People should know if the medications they're taking to treat their diabetes could lead to serious cardiovascular harm. This calls for a paradigm shift in the treatment of Type 2 diabetes."