​SGLT2 Inhibitors, Farxiga, Invokana, Jardiance and Others: Dangerous New Drugs

The FDA has approved several drugs that are part of a new class of diabetes drugs, the SGLT2 inhibitors. All have very troubling side effects. The first of these was Johnson & Johnson's drug canagliflozin, which is marketed in the U.S. as Invokana. It is also sold in a combination pill containing metformin as Invokamet.


These sodium-glucose co-transporter-2 (SGLT-2) inhibitors lower blood sugar by blocking reabsorption of glucose by the kidney and increasing its excretion in urine. However, recent findings suggest that though these drugs increase excretion of glucose, they simultaneously increase the production of glucose by stimulating the secretion of glucagon. More about that can be read HERE.


The manufacturers also claim that they cause weight loss--always a potent selling point for a diabetes drug. Most recently, a questionable research study has been the basis of the claim that one of these drugs actually prevents heart attacks. The facts are quite different, but drug company flacks are saturation bombing family physicians with materials that make it sound like they should put every patient with Type 2 on this wonderful, new drug, which is priced at $8.77 a pill or $263.10 for a monthly supply.


They shouldn't.


When the first of these drugs, Invokana (canagliflozin), came up for approval, the committee of "experts" who reviewed it were ambivalent about it because the company's own, [most likely, statistically manipulated], clinical study of patients at especially high risk of cardiovascular disease showed that within the first 30 days, 13 patients taking canagliflozin suffered a major cardiovascular event [mainly strokes and some heart attacks] compared with just one patient taking a placebo. After that, the imbalance was reversed, though the drug then caused a slight increase in LDL cholesterol. .(Details HERE and HERE)


However, as the New York Times report notes here, " F.D.A. spokeswoman said Friday that the significance of those findings was unclear, and the label of the drug includes no warnings about heart attacks or strokes."








The FDA delayed approving subsequent drugs in this family over serious concerns, but as is so often the case, eventually approved them. It was only a few years after the oldest of these drugs were in widespread use that evidence of their most serious side effects began to emerge. Since it usually takes a decade or more for the true toll of any new drug to become apparent, the number of serious side effects already associated with this family of drugs should be a serious concern.


A Questionable Study Promotes SGLT-2 Inhibitors for Kidney Disease


A 2018 study,



s being used to promote the idea that these drugs will fight diabetic kidney disease. This study was sponsored and paid for by the drugmaker. Here is a simplified report on what they found. Notice the serious complications the drug caused and the very slight lowering of A1c it produced.


It is possible these drugs are helpful for people with serious kidney disease, but you should not take them to prevent it or heart disease. The way you prevent them is by lowering your blood sugar to a level far lower than these drugs can achieve. Cutting carbs is much more effective and far, far less dangerous.

Serious Side Effects of This Entire Class of Drugs
Ketoacidosis in Type 2

The FDA issued a warning on 5/15/2015 stating that it had received a significant number of aftermarket reports linking this class of drugs to ketoacidosis. Ketoacidosis is a very serious, potentially fatal condition where the acid level in the blood rises dangerously high. Ketoacidosis makes people very sick and if untreated can be fatal. It requires a trip to the emergency room. Symptoms of ketoacidosis include: difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness.


What is particularly worrisome here is that ketoacidosis usually ONLY occurs in people with Type 1 diabetes who have very high blood sugars--those above 300 mg/dl. However, in these cases the ketoacidosis was occurring in people with Type 2 diabetes who had only modestly elevated blood sugars. It is likely that these drugs are promoting ketoacidosis because of the way they affect the kidneys, which may make it harder for the body to eliminate ketones as they build up.


Typically, people eating very low carb diets are told that as long as their blood sugar isn't high, it's perfectly safe to have raised ketone levels in blood and/or urine. But this may NOT be the case if you are taking one of these drugs because they may block the normal processes that keep ketone levels within a safe range. Until it is 100% clear what is leading to ketoacidosis in people taking these drugs it is not a good idea not to take them if you are eating a ketogenic low carb diet. You can read the entire FDA warning at:




Bone Fracture Risk and Decreased Bone Mineral Density

On Sept 10, 2015, the FDA issued a Safety Alert for Invokana and Invokamet, stating that "Bone fractures have been seen in patients taking the type 2 diabetes medicine canagliflozin [Invokana].Fractures can occur as early as 12 weeks after starting canagliflozin. Canagliflozin has also been linked to decreases in bone mineral density at the hip and lower spine."

Though the warning specifically mentioned Invokana, the oldest drug in this class, the warning bulletin also said "FDA is continuing to evaluate the risk of bone fractures with other drugs in the SGLT2 inhibitor class, including dapagliflozin (Farxiga, Xigduo XR) and empaglifozin (Jardiance, Glyxambi, Synjardy), to determine if additional label changes or studies are needed."




Note that once your bones have become weakened, it is very hard or possibly impossible to rebuild them. This side effect probably occurs because messing with how the kidneys excrete glucose also affects how they handle the minerals used build bones: phosphorus, calcium, and magnesium.


If your doctor prescribes one of these drugs, ask him or her if they are aware of these two recent FDA safety warnings. Chances are that they may have missed them.


Doubled Risk of Lower Limb Amputations

On May 16, 2017 the FDA ordered that a black box warning be added to the prescribing information for Invokana saying that it doubled the risk of experiencing an amputation. You can read the report about this very important warning in this Medscape news bulletin.

Medscape reported that The European Medicines Agency (EMA) which is the European equivalent of the FDA announced on February 10, 2017 that a warning stating that the sodium glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes may increase the risk for lower-limb amputation should be included in the prescribing information for all drugs in this class.


In Medscape's words, "The warning from EMA's Pharmacovigilance Risk Assessment Committee (PRAC) issued today cites data from two ongoing clinical trials with canagliflozin (Invokana, Vokanamet, Janssen) in patients at high risk for cardiovascular events, Canagliflozin Cardiovascular Assessment Study (CANVAS) and a related study of renal end points, CANVAS-R."


Quoting the EMA the article points out that "In a 4.5-year interim analysis of CANVAS, the independent monitoring committee for the trial found that the rate of amputations per every 1000 patients was equivalent to seven for 100 mg/day and five for 300 mg/day of canagliflozin compared with three per 1000 patients taking placebo. Most of the amputations were of toes." Note that this means that there were from one and two thirds more to more than twice as many amputations in the group taking the drug as occurred in the placebo group.


As you can see if you read the comments to the Medscape new release, some people claiming to be doctors and a pharmacist immediately argued that this was because the patients given the SGLT-2 inhibitors were sicker and more likely to have amputations. People posting comments on Medscape are not required to reveal if they are on the payroll of the companies who are earning several billion dollars a year selling these heavily advertised new drugs. Nor are they required to validate their identity, so any employee of a drug company could post these comments using a made up doctor's name.


Lest you be swayed by their arguments against believing the EMA's experts, note that this data was from a controlled study. This means that both the group taking the drug and the group taking a placebo were matched for characteristics which would have included their blood sugars, age, and time since diagnosis. Since the groups had the same characteristics, the higher rate of amputations is very likely to be a result of something the drug does to the blood supply of the toes. The EMA doesn't lightly decide to add a serious warning to the label of a drug.

Other Side Effects of This Entire Class of Drugs
Yeast Infections

Unmentioned in any of the news stories about this new drug class is the fact, mentioned in the drugs' Prescribing Information (the official FDA "Label"), that they causes serious yeast infections in women and uncircumcised men. This makes sense since sugary urine promotes the over-growth of yeast. One in ten of those who took Invokana experienced this side effect.  One in twenty who took it experienced urinary tract infections.

Decreased Kidney Function

This too is a class effect applying to all drugs in the SGLT-2 inhibitor family.. The Prescribing Information for Invokana states: "INVOKANA increases serum creatinine and decreases eGFR [glomerular filtration rate.]"  It also raises the risk of dangerous low blood pressure and hyperalkemia (high potassium levels) especially in people taking blood pressure medication. (Hyperalkemia can lead to heart rhythm abnormalities. Older people, particularly those over 75 are those most likely to have the most severe kidney-based reactions to the drug.

The Diabetes.co.uk web site describing this class of drugs also says that in the studies used for approving the drug there were more cases of liver failure, breast and bladder cancer, though the effect was not strong enough to block approval of the drug.

Effect on Blood Sugar

A low dose of Invokana (100 mg) lowered  A1c on average .79%  (i.e. from 8.0% to 7.21%. The high dose (300 mg) lowered A1c, on average .94%. In contrast, the impact of plain metformin on blood sugar, according to the Glucophage prescribing information (available HERE) is to lower blood sugar 1.4% over 29 weeks. The combination of metformin and Invokana did not make any change in the drop in A1c which remained, on average, the same as it would be with Invokana alone and far less than could be achieved with optimal metformin dosing.


Very significantly, the Prescribing Information does NOT report the effect of this drug on post-meal blood sugars when taken alone. It only reports its effect on post-meal blood sugars when taken with metformin, where it lowers blood sugar by the same amount that metformin alone would lower it. In short, Invokana does not appear to have any significant effect on post-meal blood sugars, and none, overall that couldn't be achieved by taking the cheap generic, metformin, alone. 









Farxiga, a Second, Even Worse Drug in this Same Class

Farxiga, mysteriously named "Forxiga" outside of the U.S. (both are generically named dapagliflozin) also sold as Xigduo, a combination Farxiga/metformin pill, is a second drug in this same SGLT-2 inibitor class, which has all the same side efects as Invokana, along with the possibility that it increases LDL-C, the so called "bad" cholesterol.

The FDA originally rejected it as too dangerous, but approved it in January of 2014. There were more cases of bladder cancer among those taking Farxiga than in the group that did not take it. AstraZeneca, the company selling it, assures you that the numbers in the study were too small to determine if this was statistically significant. Why would you want to participate in the much larger and, to AstraZeneca highly profitable" "study" conducted on paying human lab rats that will, by the time the patent expires on this drug, make it crystal clear just how dangerous it really is?

Jardiance, Yet Another Drug in this Class

Jardiance is the same empagliflozin that the FDA did not approve a year ago supposedly because of unspecified manufacturing problems. It was approved in August 2014.

Like the other drugs we just discussed Jardiance causes urinary tract infections and vaginal and penile yeast infection.

Misleading Claims Jardiance Prevents Heart Attacks Increase Its Popularity

The FDA demanded post-marketing cardiovascular tests, so it is likely that the same disturbing signals emerged in its clinical trials as emerged with the other drugs. However, on September 18, 2015 when the first of these cardiovascular studies was published, it generated headlines that claimed that Jardiance prevented heart attacks in people with Type 2 diabetes.


Needless to say, this was blockbuster news, since no other drug currently on the market for Type 2 diabetes can make this claim. But the truth was far more complex, and though the drug did appear to decrease heart attacks in people who were already diagnosed with significant heart disease--i.e. those who had already had heart attacks, the actual numbers were small. More importanlty, Jardiance also seemed to increase the incidence of strokes in these same people. Beyond that, this study made it clear that Jardiance did a poor job of lowering blood sugar. You can read the details about this study in This Blog Post

It is not known whether a cancer signal appeared in the clinical trials for Jardiance. But since these trials only involved a total of 4,500 people and did not last more than a few years, the cancer signal seen in other drugs in the same class should not be ignored.


Say "No" to New Expensive Diabetes Drugs!

If your doctor tries to put you on these new drugs, say no. Wait ten years, and search the literature then to see what scientists have found out about its real effects on patients before you try it.






