Quite surprising to me, I found that SGLT2 drugs have negative history with FDA. Not surprising, especially after finding the history, is the warning FDA released earlier this week. It appears that canagliflozin, sold as Invokana, may have created problems in the clinical trials that should have prevented its release.
Just as other safety problems with Invokana’s cousin, dapagliflozin, now marketed as Farxiga by AstraZeneca, did. What is now Farxiga was rejected by FDA in July 2008, but was approved for release in January 2014. Steerike two, FDA!
Then we have Eli Lilly’s Jardiance, which, in its pre-mega marketing life was called empagliflozin. FDA passed this one in August 2014 with the requirement of four post-marketing studies. Steerike three! You’re outta here, FDA!
Here’s the deal on Invokana: The FDA committee of 15 experts wasn’t really sure they wanted to approve it. AstraZeneca’s in-house study showed problems. Examining the results of the study of patients at high-risk of cardiovascular disease revealed that 13 patients had a major cardiovascular event (mostly strokes with a few heart attacks) in the first 30 days of the study! Only one patient in the control (placebo) group had a cardiovascular event in the same time period. The company tweaked the formula, lowering the risks at the expense of causing small increases in LDL cholesterol.
Even after the fix, 5 of the 15 experts still had reservations and voted against Invokana’s approval. They also noted concern that the drug might be dangerous for those with kidney disease. Incidentally, many type 2 diabetes patients have kidney disease and type 2 diabetics are the target market for the drug.
Interestingly though, an FDA spokesperson told the New York Times that the significance of the study’s findings was unclear. Therefore, no warnings of heart attacks or strokes were listed on the label. I may be of flawed understanding but I was under the impression that any possible risks were to be listed on the labels. One person catches a cold during a clinical trial? “Risk of colds = 1% in a study of 100 individuals” goes on the label. Both past contacts in the pharmaceutical industry and personal experience from participating in a clinical trial back this up.
I’m not saying the in-house study was “fudged,” but I am concerned that such important findings were excluded from public knowledge. I’m also concerned with what did make it on the label. “Invokana increases serum creatinine and decreases eGFR [glomerular filtration rate.]” This is not good for the kidneys, as those experts who voted against its approval feared.
It can also cause other side effects, such as dangerously low blood pressure. It may also cause a condition known as hyperalkemia or high potassium levels, especially in patients taking blood pressure meds. It’s important to note that potassium is one of those very important electrolytes mentioned in this post. Severe electrolyte imbalances can lead to cardiovascular events.
What are the SGLT2 inhibitors doing now? Potentially causing ketoacidosis, which involves imbalanced electrolytes and possible heart attacks or strokes.
Sounds like that original in-house study should be brought up, re-evaluated and double-checked by an impartial third party.