When a new medication comes into the marketplace, some clinicians will begin prescribing it right away while others will wait for more information.
Now that we have had the first SGLT2 inhibitor, canagliflozin, available for over three months, our Doctor of Pharmacy Candidates, Natasha Patel, Kori Lawie, Jordan Mustonen and Demetrios Pappas called over 300 clinicians across the country to find out if they were using this new drug. Over 100 of these clinicians had never heard of the drug and another 120 had heard of it but were not using it because they were not familiar enough with it. The rest felt they had enough information to make educated decisions. We have taken some of their comments to share with you, to help you decide if you would like to prescribe this medication for your patients.
Dr. Paul Norwood, MD, Endocrinologist, Valley Endocrine, Fresno, CA
“Invokana is a welcome addition to our diabetic treatments. I have written many prescriptions of Invokana. There is some mild weight loss and decrease in HbA1c of 0.8 to 1%. Copay cards make the med cost $5 for private insurance, though I consider these copay cards less desirable than a reasonable overall cost. The cost of the med is about $180 per month. Too high but I still use it. I use it third line: first metformin, second a glp-1, third Invokana, fourth insulin or actos. Usually insulin. There are few side effects. There is about a 300 cal per day loss in the urine. Normally glucose flows into the urine at 180 mg/dl; in diabetics, it flows at 240 mg/dl and with Invokana it flows at 90 mg/dl. I use it third line because there is evidence with glp-1 meds that there is some pancreatic preservation. Invokana is purely for glucose lowering.
“I wish studies were done on type 1 diabetics. I have prescribed the medication to a type 1 diabetic. My theory is that it will decrease the glucose rise. It does do this. I had the opportunity of being involved in several clinical trials with this medication thus I am very familiar with them….
“One must realize that the glucose has already passed through the glomerulus. Why is this important? The glomerulus is where the diabetic damage is in diabetics. The glucose is past the glomerulus with or without the invokana and the re-absorption of the glucose into the body is inhibited by invokana in the renal tubules. My point is if the glucose is past the glomerulus, there is no advantage in re-absorption of the calories and glucose back into the body. Thus this is why this is such a great medication. It makes a small calorie leak. It changes a diet from a 2200 calorie diet to a 1900 calorie diet.”
Dr. Morton Field, MD, PCP, Beverly Hills, CA
“I know about it but I do not know if I would use it for sugars. Patients come to me on 17 different medications and leave my office on only 2 medications so I try to get patients on as little medication as possible.”
Dr. Gregory Castello, MD, PCP, Lombard, IL
“It causes you to spill sugar in your urine and is associated with lower blood sugars and improved diabetes care. It is associated with weight loss as well because you are losing anywhere from 160-320 calories a day in your urine. Absolutely there are concerns about yeast infections, urinary tract infections and there may be some cancer risks.” “Would not recommend this drug as a weight loss drug if you are on multiple drugs for diabetes and currently uncontrolled but I do use it for my diabetes patients.”
Dr. Sanjay Kaul, MD, Brownsville, KY
Referring to FDA approval data for canagliflozin, “I questioned whether the company’s (Johnson & Johnson) use of interim data from CANVAS to seek approval for canagliflozin and then continuing the same trial post-approval was actually in compliance with the 2008 FDA guidance, which calls for completed trials.” “They’re using 1 set of end points for crossing the first hurdle, the preapproval study, then using an efficacy end point for post-approval. Technically speaking, there are some statistical issues with that.” “To me, the most interesting thing was to see how FDA is interpreting its own guidance documents… That was an interesting twist…because the guidance was not very clear on that.” “From a patient perspective, I believe that the 4 to 7-fold increased risk for genital mycotic infections seen with canagliflozin, is what will make or break the drug once it’s on the market.” Although treatable, “It’s not appealing. That’s what I think…we’ll see.” “Nonetheless, “I think the FDA did the right thing and has demanded an array of post-approval studies, and I am currently prescribing the medication.”
Dr. Alan J. Garber, MD, Endocrinologist, Houston, TX
“Canagliflozin provides another therapeutic option for patients with type 2 diabetes. This option is beneficial since it’s not dependent on endogenous insulin secretion, has no proclivity for excess risk of hypoglycemia, and is generally associated with modest weight reduction.” “At this point I use canagliflozin as a second-line agent following metformin and lifestyle modification or for patients who can’t tolerate metformin.” “At the present time, the only other category of agents about which we can get enthusiastic are the incretins — the GLP-1 agonists and DPP-4 inhibitors — I would see an SGLT2 inhibitor competing in that same space.” Regarding the risk of UTIs, cancer, and other unknown adverse events, “You have to treat the diabetes with something. Regardless of what it is you choose, all of those ‘somethings’ are associated with adverse events… There’s no medication that’s free of any concern, but there is, of course, lots of concern about untreated diabetes. So you just have to find the best medication that suits the patient’s profile and try to make a good match that way.”
Dr. Fernando L. Gonzalez, MD, South Bend, IN
“Canagliflozin was associated with significantly higher rates of genital mycotic infections in both men and women, as well as more adverse events related to osmotic diuresis. The infections were symptomatic, easily diagnosed, and readily treated with topical or oral antifungals.” “The adverse events related to increased urination were typically mild. These side effects led to very few study discontinuations,” said Dr. Gonzalez. “The mechanistic studies have identified two factors as being responsible for the clinically meaningful reductions in blood pressure seen with canagliflozin in this study, which amounted to a mean 3.5 mm Hg decrease in systolic blood pressure at 100 mg/day and a 4.7 mm Hg reduction at 300 mg/day.” “It appears that about half of the blood pressure reduction is due to the negative salt and water balance, on the order of 750-1,000 cc, occurring in the first 3-4 days of treatment, and the other half is related to the weight loss accompanying canagliflozin therapy.” “I like the medication and use it in my practice.”
Dr. Ralph A. DeFronzo, San Antonio, TX
“It’s a widespread misconception that the medications are associated with an increased risk of urinary tract infections.” “It’s very commonly stated that this class of drugs is associated with an increase in UTIs [urinary tract infections]. In fact, if you look at the data rather than what’s said, this really in my opinion doesn’t hold up. You can see it in the studies, where there’s no significant difference between the groups.” “I am very optimistic about this medication and class of drugs and use it with no reservations.”
Mayer Davidson, MD, Charles R. Drew University in Los Angeles, CA
“I think that there’s a real niche for this class of drugs.” “In addition to canagliflozin’s effect on HbA1C, patients get two other benefits as well: weight loss and a 5-mm drop in systolic blood pressure.” “But a 10% to 15% genital infection rate is something to consider.” “The treatment protocol at our center requires giving metformin first and then adding a sulfonylurea if a second drug is needed.” “If that doesn’t work, we add a third drug — at the moment, a [thiazolidinedione] TZD. As you know, there are a lot of contraindications for TZD — that’s where I currently use canagliflozin in my practice, as a third drug.” “This is a unique drug, because all the other drugs depend on the beta cells to secrete insulin, [which] over time, get weaker, so eventually that’s why people have to go on insulin.”