Dapagliflozin for Type 2 Diabetes, Do You Need This Drug?
It appears the Food and Drug Administration (FDA) will probably approve dapagliflozin (Forxiga) for treatment of type 2 diabetes after an FDA advisory panel voted 13-1 in favor of approval on December 12, 2013. But do people with type 2 diabetes need another drug to join the already overflowing medicine chest of oral antidiabetes options?
What is dapagliflozin?
Dapagliflozin is the child of AstraZeneca and Bristol-Myers Squibb Company and is yet another drug that can be used along with diet and exercise, with or without other antidiabetes drugs, to support management of glycemic control in adults who have type 2 diabetes. The date of the expected decision is January 11, 2014.
The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee also voted 10-4 that the data provided by the drug companies was sufficient to show that the drug has an acceptable risk profile for cardiovascular events such as stroke and heart attack. That decision was reached even though there is an ongoing study (DECLARE) of that risk that is not scheduled to end until 2019.
DECLARE is a double-blind trial that involves about 17,000 individuals, and the purpose is to evaluate the effect of dapagliflozin on people with type 2 diabetes who are taking other antidiabetes medication to determine the risk of cardiovascular events, including death, when compared with placebo. If dapagliflozin is approved now, the results on its cardiovascular risks from this trial will not be available for five years, unless the study is stopped early.
Currently, dapagliflozin (under the trade name Forxiga) is approved for use in 38 countries.
How dapagliflozin works
Dapagliflozin is in a drug class called a sodium-glucose cotransporter 2 (SGLT2). The drug works by inhibiting subtype 2 of a substance called sodium-glucose transport proteins, which are responsible for most of the reabsorption of sugar (glucose) in the kidneys.
Since the kidneys of people with type 2 diabetes have a 20 to 30 percent increased ability to reabsorb glucose, they are at an elevated risk of high blood sugar. A drug such as dapagliflozin reduces the reabsorption of the extra sugar, which then allows it to leave the body in urine.
Because the drug causes an excess of sugar in the urine, significant side effects of its use include an increased risk of urinary tract infections and candidiasis. Other side effects can include tiredness, weight loss, drop in blood pressure, and dehydration.
Troubles with dapagliflozin
Dapagliflozin had been presented to the FDA advisory committee back in July 2011, but the panel voted 9 to 6 against recommending its approval because of evidence of an increased risk of bladder cancer. Specifically, 10 patients in the treatment group developed bladder cancer compared with only one in the control group.
At that time, the reviewers noted they “could not conclude with any level of confidence that the purported (cardiovascular) benefit associated with dapagliflozin use outweighed the observed imbalance in specific malignancies or potential liver toxicity risks.”
Now, however, the resubmission of the New Drug Application for dapagliflozin included new research study results that addressed these concerns. The studies involved more than 11,000 adults with diabetes, including some who were elderly, overweight, obese, or hypertensive as well as those with renal problems or a history of cardiovascular disease.
Since dapagliflozin provides only “modest but statistically significant reductions in glucose” and some weight loss help, why do people with type 2 diabetes need another drug, especially one with a gray cloud hanging over its head? And because new drugs cost more than many of the tried-but-true diabetes options on the market (including generics), does the public need another diabetes drug?
Results of a dapagliflozin study
In a randomized, double-blind trial, 406 people with type 2 diabetes were given at least 10 mg per day of dapagliflozin while 408 patients were given at least 20 mg per day of glipizide along with metformin. After one year, both groups had similar changes in hemoglobin A1c while dapagliflozin was associated with weight loss and less risk of hypoglycemia.
A review of four-year data from the study included 161 patients taking dapagliflozin and 141 taking glipizide. An analysis showed that:
- Patients taking dapagliflozin showed an average weight loss of 3.95 kilograms (nearly 9 lbs) compared with an average of 1.12 kilogram (2.7 lb) weight gain in the glipizide patients
- Mean systolic blood pressure declined in the dapagliflozin group but not in the glipizide group
- Ten times fewer patients in the dapagliflozin group experienced hypoglycemic events than those in the glipizide group
- Discontinuation of medication due to side effects was 13.3 percent in the dapagliflozin group and 11.3 percent in the glipizide group
- Urinary tract infections developed in 13.5 percent of patients taking dapagliflozin and in 9.3 percent of those in the glipizide group
People with type 2 diabetes should do their own research on medications and then discuss any medication decisions with their healthcare provider. However, that does not mean anyone whose doctor suggests dapagliflozin (if approved) should not ask questions about why it is being recommended, what the risks are, and what the advantages would be over other medications or incorporating more lifestyle changes.