Invokana (canagliflozin) – A New Medication for Diabetes

Invokana was approved by the FDA in March 2013 to help control blood sugar in patients with type 2 diabetes. Here is a quick overview of the medication for any diabetics or caregivers that might be interested in the drug. This does not represent all of the information you need to know about the medication, so please consult your doctor, pharmacist, and medication guide for information.   You can always send me an inquiry by using our contact form:

How does it work?

Invokana works in a way that is completely different than any other diabetes medication that is currently available. It inhibits the activity of a protein located in the kidneys called sodium/glucose cotransporter 2, or SGLT2 for short. This protein is responsible for carrying glucose out of the urine that is being formed in the kidneys to the walls of the tubes in the kidneys, where it is reabsorbed into the blood. This results in a good bit of glucose being “peed” out, which means less glucose staying in the bloodstream.

How effective is it?

In studies, Invokana reduced A1C levels 0.62% points at 100 mg daily and 0.77% points at 300 mg daily when added to metformin. This is similar to a lot of the other newer diabetes medications, but not as effective as metformin itself, sulfonylureas (such as glipizide and glyburide), and not nearly as effective as insulin.

What are the side effects?

The major side effect seen with Invokana has been urinary tract infections and vaginal yeast infections. This is likely due to the increased glucose in the urine, which promotes the growth of fungi and bacteria. It can also cause increased urination, as the extra glucose draws more fluid into the tubes of the kidneys (creating more urine). This increased urination can also cause dehydration, decreased blood pressure, and abnormal electrolyte levels (mainly increases in potassium). It can also increase LDL (the bad cholesterol). There is currently an investigation as to whether or not it increases the risk of stroke in the first month of treatment, as was seen in one analysis.

Invokana obviously decreases glucose levels, and by itself or in combination with metformin it is unlikely that it will reduce glucose to dangerously low levels (referred to as “hypoglycemia”). But if combined with insulin or other diabetes medications, it may increase the risk for hypoglycemia.

A good side effect, at least for most diabetic patients, is weight loss. This is probably due to a combination of fewer calories absorbed from glucose and the fluid losses from increased urination. This weight loss looks to average 4 to 7 pounds from the studies done so far.

This drug hasn’t been studied over a very long period of time, so it is possible that severe side effects exist that haven’t been detected yet. This has happened with several diabetes medications in recent history. For this reason, the FDA is requiring the manufacturer of Invokana to continue to study the medication to see if any severe side effects develop over time, especially relating to cardiovascular disease, bone health, and pancreatitis.

What drugs does it interact with?

Invokana is broken down in the body by an enzyme called UGT. Some drugs increase the activity of UGT, which would result in decreased effectiveness of Invokana. These drugs include rifampin, phenytoin, phenobarbital, and ritonavir. As mentioned earlier, when added to drugs that reduce glucose levels, Invokana may increase the risk of hypoglycemia. ACE inhibitors, ARBs, spironolactone and eplerenone increase potassium levels, so the effect would be additive when combined with Invokana. Also, Invokana can increase digoxin levels, so close monitoring of digoxin levels is advised.

Who should avoid it?

Invokana is best avoided by certain people. People with significant kidney disease shouldn’t use it: it won’t work well (due to reduced ability to make urine), may worsen kidney function, and those patients are at a higher risk of dangerously high potassium levels. If you have high cholesterol that is poorly controlled or recurrent urinary tract infections, Invokana is probably a poor choice for you. Data in pregnancy is lacking, so I’d advise against use in women who are or may be pregnant. It hasn’t been studied in type I diabetes, so use should be limited to type II diabetes for now.

The Medicine Guy says:

This is a promising new medication. Its mechanism is really neat, and in theory has a lot of advantages. The weight loss is a big plus, as well as a reduced propensity to cause hypoglycemia when compared to some older diabetes meds.

That being said, I don’t think I’d recommend this drug for the majority of patients at this time. Metformin should be the first line therapy in all type II diabetics who need treatment unless contraindicated. It is more effective, much cheaper, and time tested in terms of safety. Second-line therapy for a good majority of patients should be a sulfonylurea in my opinion, as they are much cheaper and more effective as well (although they do carry a higher risk of hypoglycemia). For patients who need more aggressive glucose control after first or second-line therapies, insulin is usually the way to go.

Invokana would be an option (as well as newer drugs like Onglyza and Januvia) for patients who aren’t well enough controlled on metformin and don’t want to use insulin and who meet the following criteria: have good insurance coverage and/or don’t mind the cost, are at highest risk for hypoglycemia, and don’t mind the uncertainty about long-term safety.

I’d love to hear what you think in the comments section. Also, tweet a response to @themedicineguy.

Dr. Emmel

Author: themedicineguy

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  1. How many days at 100/day before Invokanna becomes effective – i.e., reduction in daily BG tests?

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    • Hi Debra,

      According to a small study, Invokana results in a significant drop in BG tests within the first 24 hours of the first dose. This effect appears to improve slightly over the first week of treatment (reference: Devineni, Damayanthi, et al. “Pharmacokinetics and Pharmacodynamics of Canagliflozin, a Sodium Glucose Co‐Transporter 2 Inhibitor, in Subjects With Type 2 Diabetes Mellitus.” The Journal of Clinical Pharmacology (2013).) Considering the manner in which this medication works, this sounds about right.

      Keep in mind that the major studies with Invokana show a reduction in Hba1c levels of about 0.5 to 0.7, which is approximately a 15-20 point drop in average blood glucose.

      Post a Reply
  2. Im allergic to sulfa base meds …. does invokana have any traces of sulfa ingredients?
    Im a type 2 diabetic and have been working very hard to keep my blood sugars in the 100s and below my goal is to get off insulin injection of humalog and lantusmm.recently my A1C is 5.5..

    Post a Reply
    • Sulfa allergy is not a contraindication to Invokana.

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  3. Hi. I have been on this for three weeks and now have two bacterial infections. I am wondering if I should go off this drug. My sugars have been amazing.

    Post a Reply
    • Hi Gerry,
      That is a discussion you should have with your physician. There appears to be an association between Invokana and urinary tract infections, so if the infections you are referring to are UTIs than you should certainly have that discussion with your doctor. There are many options for treating diabetes now, and given the marginal effectiveness of Invokana there might be a better option if you are experiencing a known side effect.

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