New type of diabetes drug in pipeline, but safety issues exist
On January 11, a Food and Drug Administration (FDA) advisory panel voted 10 to 5 to approve a new type of diabetes drug, canagliflozin; however, several panel members, including some who voted in favor of approval, raised concerns regarding harm to the kidneys or cardiovascular system. Unlike conventional medications for diabetes that work by stimulating insulin production, canagliflozin increases the excretion of glucose into the urine by the kidneys. The drug is under development by Johnson & Johnson and if approved will be marketed as Invokana.
Clinical trials of more than 10,000 individuals worldwide have reported that the medication improved blood-sugar levels and also resulted in weight loss and reduction of blood pressure. The drug is aimed for adults suffering from type 2 diabetes and would be taken once a day. One concern raised by doctors on the panel was that it should not be used on patients with impaired kidney function. A study of this group of people found that canagliflozin was not as effective on them as it was for those with normal kidney function. In addition, the panel felt that the drug was inappropriate for use on patients with severe kidney disease.
The clinical trials raised other concerns for the drug including an elevated risk of strokes, heart attacks, and other cardiovascular problems within the first 30 days of use. In addition, canagliflozin was found to raise LDL (“bad cholesterol”) levels; however, it also raised the levels of HDL (“good cholesterol”). The votes of the panel members indicated whether or not they felt the benefits outweighed the risks. Some noted that the FDA could address such concerns by requiring Johnson & Johnson to include appropriate warnings with the drug if it is eventually approved. The FDA is not required to follow the recommendations of its advisory committees; however, it usually does.
The drugs currently on the market to treat diabetes, including insulin, also have side effects such as weight gain and hypoglycemia, or a dangerously low blood sugar level. The subjects in the canagliflozin clinical trials experienced fewer episodes of hypoglycemia compared to those taking another diabetes drug, glimepiride, or Amaryl, but a similar rate compared to patients taking the drug sitagliptin, or Januvia.
Dr. Peter Stein, the diabetes disease area leader for Janssen, Johnson & Johnson’s pharmaceutical division, noted that he was gratified that the panel voted to approve the drug and said the company would continue to monitor patients for potential safety risks. He explained, “We have a strong belief that canagliflozin is a medication which really offers a new option for Type 2 diabetes patients.”
Dapagliflozin, manufactured by Bristol-Myers Squibb and AstraZeneca, was rejected by the FDA in 2012 because of safety concerns, including a possible increased risk of breast and bladder cancers. However, it was approved in Europe in November 2012 under the name Forxiga.
Take home message:
Diabetes is basically a lack of sufficient inulin and/or a resistance to insulin, which is necessary to metabolize glucose. Canagliflozin rids the body of some of its circulating insulin. Thus, the question becomes: why not put less glucose into one’s body? Many type 2 diabetics are overweight or obese; thus, if they ate less and lost weight, their diabetic condition could be improved or resolved. In addition to the renal (kidney) cardiovascular risks addressed by the panel, the drug has another risk. Glucose is also a nutrient for bacteria; thus, kidney and bladder infections are more likely to occur with its presence in the urine.
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