New Drugs Make Diabetics Pee Out Excess Sugar

man and woman toilet sign

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.”

  • Marry

    I was diagnosed with type 2 Diabetes and put on Metformin on June 26th, 2014. I started the ADA diet and followed it 100% for a few weeks and could not get my blood sugar to go below 140. Finally i began to panic and called my doctor, he told me to get used to it. He said I would be on metformin my whole life and eventually insulin. At that point i knew something wasn’t right and began to do a lot of research. On April 13th I found this book on
    w­j­e­5­9­2­.­com/Cure-Diabetes-Naturally.html . I read the book from end to end that night because everything the writer was saying made absolute sense. I started the diet that day and the next morning my blood sugar was down to 100, the next day was in the 90’s and now i have a fasting blood sugar between Mid 70’s and the 80’s. My doctor took me off the metformin after just one week of being on this lifestyle change. I have lost over 30 pounds in a month. I now work out twice a day and still have tons of energy. I have lost 6+ inches around my waist and I am off my high blood pressure medication too. I have about 20 more pounds to go till my body finds its ideal weight. The great news is, this is a lifestyle I can live with, it makes sense and it works. God Bless the writer. I wish the ADA would stop enabling consumers and tell them the truth. You can get off the drugs, you can help yourself, but you have to have a correct lifestyle and diet. No more processed foods.

    • Ez Acosta

      It pays to advocate for our own health. The standards of health in conventional medicine is atrocious. Im glad you found the path out of sickness. So much of this countries ills goes back to nutrition and clean living and food. The truth is out there.

  • Kimberly Ryan

    In 2007, I was diagnosed with severe fibromyalgia, placed on narcotic therapy, extremely active, petite, until three years ago. Cannot take Lyrica or gabapentin due to severe allergies and Cymbalta doesn’t help. I was taken off these medications because of all the studies contraindicated their effectiveness. Now I’m not on anything. I’ve gained almost 50 pounds, due to decreased activity, in severe pain, have increased neuropathy and muscle weakness, all of which are not being addressed. To add fuel to the fire, I had a brain aneurysm in 4/2000 which left me with traumatic brain injury, as well as, physical side effects. I’ve kept these to a minimum by staying physically fit and active. Because my health has deteriorated and by not being as physical, these side effects are becoming more apparent again. There is no one treating fibromyalgia in my area and I also live in NYS with the strict regulations of narcotics. I don’t fit the “normal” treatment for this diagnosis, nor do I have a history of alcohol or drug abuse, yet I cannot get help. It’s unfortunate that someone who goes from being highly active all their life, athletic, loves the outdoors, lives alone, owns their own house, used to be an RN, becomes someone who struggles to get through the day. It’s not right.