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New Drugs Make Diabetics Pee Out Excess Sugar

Modest weight loss is an added benefit

An abnormally high level of sugar in your urine has traditionally been a sign of uncontrolled diabetes and something to be corrected. But that notion has been turned on its head by a new class of diabetes drugs that work by increasing how much sugar patients pass in their urine.

New path to blood sugar control

To date, two of these new drugs have been approved by the U.S. Food and Drug Administration for treating type 2 diabetes. The first, canagliflozin (Invokana®), was cleared last March; the second, dapagliflozin (Farxiga®), was approved just this week.

Both drugs are so-called SGLT2 inhibitors that act by blocking the kidneys’ reabsorption of sugar, or glucose. The result is that more glucose is released in the urine and the patient’s blood glucose level goes down — a major goal of diabetes treatment.

Most other available drugs for diabetes work by targeting the liver, pancreas or gut to improve insulin sensitivity, reduce insulin resistance or stimulate insulin secretion. In contrast, SGLT2 inhibitors work completely independent of insulin.

The two new medications, which are taken by mouth in pill form, are approved for use as stand-alone drug therapy, in addition to changes in diet and increased exercise, or in combination with other drugs for diabetes. Their approvals were based on multiple clinical studies — nine for canagliflozin and 16 for dapagliflozin — showing that they effectively lowered hemoglobin A1c, a measure of average blood sugar level over the previous three months.

A surprise effect on the waistline

An added benefit is that SGLT2 inhibitors are associated with modest weight loss. For instance, patients shed from 2.8 percent to 5.7 percent of body weight in clinical studies of canagliflozin.

“The weight loss is an appealing side effect of SGLT2 inhibitors, especially in the growing population of obese individuals with type 2 diabetes,” says Cleveland Clinic endocrinologist Mary Vouyiouklis, MD. “Aside from metformin, which occasionally results in modest weight loss, other oral drugs used to treat type 2 diabetes are weight-neutral or can cause weight gain.”

Safety profile: Keeping an eye on heart effects

Another potential benefit is also a potential adverse effect: the fact that SGLT2 inhibitors have a mild diuretic effect (i.e., tend to increase urination). This results in lowering of blood pressure, which can be good for some patients who have high blood pressure but can also cause lightheadedness, dizziness or even fainting in other individuals. Dr. Vouyiouklis says caution is needed before these drugs are started in any patients at particular risk of the latter effects, such as the elderly or patients taking diuretics or multiple drugs for blood pressure.

The drugs’ other most common side effects in clinical trials — genital yeast infections and urinary tract infections — are also related to the fact that they act via the kidneys. Both drugs posed a low risk of hypoglycemia, the dangerously low blood sugar episodes associated with some diabetes therapies.

However, the new drugs were found to modestly increase levels of LDL (“bad”) cholesterol, which could be a concern because patients with diabetes are already at increased risk of heart disease. The potential for increased rates of heart attack, stroke and other cardiac events is being specifically monitored in large ongoing studies of both canagliflozin and dapagliflozin, but full results are not expected for several years.

Ongoing bladder safety scrutiny with dapagliflozin

Additionally, patients taking dapagliflozin in clinical trials showed a small increase in bladder cancer diagnoses compared with control patients. In fact, dapagliflozin was rejected for approval by the FDA two years ago because of concerns over bladder cancer and liver toxicity.

The agency’s concerns about these risks were eased by additional data from dapagliflozin’s manufacturer this time around, but the drug’s approval included a requirement that it be studied for bladder cancer risk in patients in ongoing trials as well as in new animal studies looking specifically at effects on the bladder.

Canagliflozin does not appear to be associated with bladder cancer or liver toxicity, the FDA concluded.

More agents in the pipeline

Several other SGLT2 inhibitors may soon be available as well. One of them, empagliflozin, is in late-stage studies, and the FDA is expected to decide on its approval by the end of March.

Who should get these drugs, and when?

Dr. Vouyiouklis says obese patients with type 2 diabetes and normal kidney function stand to benefit most from SGLT2 inhibitors. In general, these drugs seem to be best tolerated by patients with normal kidney function and less well tolerated by those with moderate kidney disease (they should not be used by patients with severe kidney disease). They are not approved for use by pregnant women, patients under 18 or individuals with type 1 diabetes.

“Although SGLT2 inhibitors are approved for use as single drug therapy, metformin remains my choice for first-line oral therapy,” says Dr. Vouyiouklis. “Because SGLT2 inhibitors are relatively new and their long-term effects are not yet known, I prefer to reserve them for use as add-on therapy. I believe they will be a useful addition, especially in obese patients who are seeking to lose weight.”

Tags: diabetes, Type 1 diabetes, Type 2 diabetes
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  • Carley

    I can foresee uncontrolled diabetics with type 2 getting worse with the thought of eating what they want without worry of increased insulin release and peeing out the excess sugar…Just hope the docs monitor what they eat and enforce food nutrition and not use this as a weight loss scheme!

    • delicate white.

      That is a very sizeist assumption. You are assuming that obese people are not intelligence. Discriminating against obese people doesn’t help them.

      • winston smith

        siseist??? really? what new name can fools with to much time on their hands come up with?

    • ashley38370048

      Ever heard for testing? The above comment is just silly. Intelligent diabetics test often and NEVER indiscriminately eat anything they want. BTW, diabetics do not worry about “increased insulin release”. Do you even know what you are talking about?

    • Christa

      Carley, have you ever been obese?? If you have not you have no clue what obese people go thru. Even if you are a dietician, if you have never been significantly overweight, you have no clue how hard you have to work against the ‘fat gene”. Yes there is such a thing as the fat gene. It is thru my entire family along with diabetes. Obese people have to work at nutrition and fighting for weight loss 4 times as much as other “normal people”

      I get so tired of the talk from persons who have never had s weight problem . So Unless you have been an obese person, save our comments for something you actually have experience on. This is not one of those things.

    • Thor

      Doctors can’t enforce food nutrition. They can monitor your weight, blood, etc, and send you to a nutritionist or psychologist but thats about as far as they can go. Its up to the individual to enforce what they put in their mouth at meal and snack time, not the doctor, nutritionist, or counselor.

  • Treatment Diaries

    Diabetics have a lot to deal with. Exchanging insight and encouraging one another goes a long way toward adherence and well being.

  • Tia Singleton

    Can this drug assist pre-diabetic patients?

    • BillC

      If you do a search for Invokana Reviews, there’s a fair number of prediabetic people who are saying they’re getting really good results when combined with diet and exercise.

    • miamirn

      Thanks for posting this!

  • david k

    The new drug has indeed helped me losing the sugar level, which was not possible with other drugs over time.

  • David Becknell

    Being a 10 year diabetic battling my weight and blood sugar, this looks promising. My new doctor recommended this for me today. I guess we will see after my blood work.

    • BillC

      Saw my diabetic nurse yesterday and she’s going to ask my doctor about putting me on it. Apparently it works quite well from what she said. 0.5 to 1.0 lower A1c plus weight loss… Count me in!

  • Sue Phillips

    My endo suggested I add the farxiga and after researching it and reading alot of user reviews I declined. So many side effects I do not want. Yeast infections are debilitating for me. Sometimes it takes me a complete month for them to go away. I can’t and won’t suffer like that. Men do not know the pain they cause. There is no way I want to take a drug that increases my bad cholesterol….dr would increase statin dose to the point I won’t be able to lift my arms or legs from muscle pain. Do I want bladder cancer as well? This drug was rejected 2 yrs ago by the FDA, now it is OK? It has not been on the market long enough to determine longterm side effects. I do not want to be the governments guinea pig.

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  • Craig Galat

    I can see myself benefiting greatly from this.

  • ashley38370048

    I’ve been in a clinical trial for Farxiga® and couldn’t be happier with the result. My blood sugar is under much better control as I now target 70 instead of 100 as before. I’m no longer gaining weight and am actually hoping that I can someday lose enough to get rid of diabetes.

  • Jusu

    My Dad a diabetes patient but very thin, so can too take these pills.

  • Segopotso Tiro

    Are the drugs available in South Africa