SGLT-2 Inhibitor—Invokana

Is Invokana Right for You?

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Invokana (canagliflozin) belongs to a class of drugs known as sodium glucose co-transporter 2 (SGLT2) inhibitors and was the first of the SGLT-2 inhibitors to be approved by the FDA in the spring of 2013. Invokana, an adjunct to diet, and exercise can help to lower blood glucose. SGLT-2 inhibitors work with the kidney by sending glucose (sugar) out of the body through the urine. Sugar is reabsorbed by the kidney and, instead of re-entering the blood stream, it is excreted via the urine.

Since approval, studies have shown that Invokana can cause some serious adverse effects that have been added to the black box warning including, acute kidney injury, bone fracture, and an increased need for lower limb amputations. These risks appear to be higher with Invokana than with the other two drugs in this class (empagliflozin or dapagliflozin). On the flip side, some research suggests that Invokana appears to confer a lower risk for future cardiovascular (and renal) events in people with type 2 diabetes, regardless of whether they already have cardiovascular disease. Therefore, prescribing this medication can be a bit controversial. It's important to have a keen understanding of how this medication works and if it is right for you. 

What Does the SLGT-2 Protein Do and Why Should We Inhibit It?

SGLT-2 is the protein that helps to reabsorb sugar in the kidney. In fact, ninety percent of reabsorption occurs through SGLT-2.

The SGLT-2 protein is similar to a tunnel, and when the tunnel opens, glucose that has been filtered through the kidney can travel back to the blood stream. Normally, we want to reabsorb glucose so that other important nutrients in the kidney are not filtered into the blood stream. However, people with diabetes have too much SGLT-2 and the body is unable to spill some of the glucose into the urine, therefore all the sugar is sent back into the bloodstream contributing to elevated blood sugars.

  

Researchers have sought to inhibit the SGLT-2 protein so that excess sugar can spill into the urine and not into the blood stream. The inhibitor in Invokana is called, canagliflozin. Canagliflozin turns off SGLT-2 proteins mechanism of action and causes excretion of glucose in the urine. 

How Can This Medicine Help Me?

As with any medication, you must weigh the positives and negatives before taking Invokana. Studies have shown that Invokana can help to lower HgbA1c by 0.7-1 percent. In addition, by excreting glucose into the urine, your body isn’t using that sugar as fuel, so weight loss is possible. Invokana may also help to reduce blood pressure, and some studies also suggest that Invokana can help to increase good cholesterol. But there's still not a great deal of long-term safety and efficacy data for the drug, and like all medications, there is a risk of side effects. 

What are the Side Effects?

According to The Food and Drug Administration, the most common side effects of Invokana include:

  • dehydration
  • vaginal yeast infections
  • low blood pressure
  • penis yeast infections 

Other potential side effects include:

  • increased risk for lower limb amputations
  • acute kidney injury
  • bone fractures

You should not take Invokana if you are allergic to any of its ingredients (read package insert), if you have severe kidney problems, are on dialysis, or have neuropathy, peripheral vascular disease, or a history of foot ulcers.

Your doctor should do a blood test to assess your kidney function before prescribing this medication—dosages can be altered depending on the result. You’ll also want to tell your doctor if you are following a low-sodium diet, are pregnant or plan to become pregnant, or are breastfeeding. Lastly, inform your doctor or Certified Diabetes Educator of all your medicines, supplements, and herbal remedies. Invokana can affect how well your medicines work and vice versa.

Alert your doctor if you take any of the following: 
•     diuretics (water pills) 
•     rifampin (used to treat or prevent tuberculosis) 
•     phenytoin or phenobarbital (used to control seizures) 
•     ritonavir (Norvir®, Kaletra®, Lopinavir ®)* (used to treat HIV infection) 
•     digoxin (Lanoxin®)* (used to treat heart problems)  

How Will I Take the Medicine? 

Currently, a lack of long-term data inhibits the use of Invokana as the first line of treatment when it comes to choosing diabetes medicines. Instead, if your physician decides that Invokana is the right medicine for you, it will likely be added as a second agent. For example, if you are using Metformin and your blood sugars are not at goal, your physician may add on Invokana, However, because of the long list of side effects, many physicians are deciding to choose other SLGT-2 inhibitors over Invokana. 

If, however, your physician believes this medication is right for you, Invokana is prescribed as 100mg or a 300mg dose. The medication should be taken before the first meal of the day. 

Can I Afford Invokana?

Invokana remains a costly medication. But, the good news is that some people may be eligible for programs that can aid in reducing the cost. If you have private or commercial health insurance, you may be eligible for The Invokana CarePath Savings card provided by Janssen Pharmaceuticals (the manufacturer of the medication). This card can help reduce your cost to a zero dollar co-pay. For more information about this saving go to: https://www.invokana.com/cost-support-resources. Other ways to save cost on this medication is to look into patient assistance programs offered by Johnson and Johnson  or research your state pharmaceutical assistance programs (SPAPs). These types of programs are state specific but can help residents pay for their drugs. 

Other Important Things You Should Know: 

  • Invokana also comes as a combination medication which includes Invokana and Metformin: Invokamet, Invokamet XR.
  • Invokana works best when used in conjunction with diet and exercise.
  • Because Invokana causes extra sugar to be excreted in the urine, you will test positive for sugar on a urine test.
  • Excess sugar in the urine can cause yeast infections and urinary tract infections. 
  • Invokana can cause elevated potassium levels in the blood. 
  • If you are taking Invokana with another hypoglycemic agent such as insulin or a sulfonylurea your chances for low blood sugar are increased. 
  • You may feel the urge to urinate more or have a larger urine output when taking Invokana.
  • Invokana is not meant for people who have ketoacidosis. 
  • Call your doctor is you are experiencing any side effects that are bothering you and do not go away. 

Other Medicines of This Class:

  • Dapagliflozin (Farxiga®)
  • Empagliflozin (Jardiance®)

For more information about oral diabetes medicines: All About Oral Diabetes Medicines

Sources:

Mahaffey KW et al. Canagliflozin works as both primary and secondary prevention in patients with diabetes type 2. Circulation.2017 Nov 13

U.S. Food and Drug Administration. FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR).

Gebel, Erika, Ph.D. New SGLT-2 Meds Target the Kidneys. Diabetes Forecast

Gustaitis, Joseph. Affording Invokana. Diabetes Self Management. 2013; 33. 

Schernthaner, Guntram, et al. Canagliflozin Compared With Sitagliptin for Patients With Type 2 Diabetes Who Do Not Have Adequate Glycemic Control With Metform Plus Sulfonylurea: A 52-week randomized trial. Diabetes Care