The Food and Drug Administration (FDA) has given its seal of approval to Boehringer Ingelheim’s Jardiance (empagliflozin) tablets, as an addition to diet and exercise for adults with Type 2 diabetes.
Type 2 diabetes affects about 26 million people and accounts for more than 90 percent of diabetes cases diagnosed in the United States. Over time, high blood sugar levels can increase the risk of serious complications, including heart disease, blindness, and nerve and kidney damage.
Dr. Curtis J. Rosebraugh of the FDA’s Center for Drug Evaluation and Research said in a press statement, “Jardiance provides an additional treatment option for the care of patients with Type 2 diabetes. It can be used alone or added to existing treatment regimens to control blood sugar levels in the overall management of diabetes.”
Jardiance is a sodium glucose co-transporter 2 (SGLT2) inhibitor. It works by blocking the reabsorption of glucose (blood sugar) by the kidneys, increasing glucose excretion in urine, and lowering blood sugar levels in people with diabetes. The drug’s safety and effectiveness were studied in seven clinical trials of 4,480 patients with Type 2 diabetes. The trials showed that Jardiance improved hemoglobin A1c levels (a measure of blood sugar control) compared to a placebo.
Dr. Gerald Bernstein, director of the diabetes management program at the Friedman Diabetes Institute at Beth Israel Medical Center, and an associate clinical professor of medicine at the Icahn School of Medicine at Mount Sinai in New York, told Healthline, “Years ago, a primary goal of diabetes treatment was to keep glucose out of the urine. The ability to do self-blood [glucose] testing is a much better way to monitor, and people don’t have to check their urine as much. In recent years, a new category of drug that causes the body to spill glucose in the urine in a controlled way has emerged. It is normal for a lot of glucose to enter the kidney, but before it gets into the urine, it is reabsorbed back into the bloodstream.”
Bernstein added, “[Jardiance] is an additional drug in that category. This drug blocks a limited amount of that reabsorption so that glucose does spill into the urine. Two things occur. The glucose level in the blood is reduced, and some calories are wasted. Over time that could mean a better A1c and a slow, safe loss of weight. It is approved for use in addition to good nutrition and exercise. It is always good to have an additional version of a drug. The fact that its cousin has been in use and has so far been safe should ease its clinical acceptance.”
Jerry Meece, R.Ph., CDE, and owner of Clinical Services at Plaza Pharmacy and Wellness Center in Gainesville, Tex., who has incorporated diabetes care into his pharmacy practice, told Healthline, “Jardiance is the third SGLT2 inhibitor introduced; the other two are Invokana (canagliflozin) and Farxiga (dapagliflozin). What we used to think was a bad thing, having a lot of glucose in the urine, ends up [when you are taking this drug] being a sign of new possibilities. It drops A1c in the neighborhood of one percent.”
According to Meece, SGLT2 inhibitors are unique in that they are the only class of drug that is insulin independent. “Every other oral drug requires some relationship with insulin. This drug works as an insulin independent drug, meaning that regardless of where you are in the disease state, or how long you’ve had diabetes, it works basically the same way. The only limiting factor being renal disease, or renal involvement,” said Meece.
One of the benefits of Jardiance is that it helps with weight loss without causing hypoglycemia, or a dangerous drop in blood sugar levels, said Meece. “When you are basically urinating glucose, you are urinating calories, and you lose 200 to 300 calories per day taking this drug. It does it without causing hypoglycemia, and that’s not a small thing to overlook, because hypoglycemia itself ends up causing a lot of admissions every year to the emergency department,” he said.
Meece is also enthusiastic that Jardiance is what he dubs “durable.” “You take it now and a year from now it is working like when you started taking it. That’s a good thing. With a lot of drugs, when you start taking them it’s just a matter of months to a year when they are not as effective as they were,” he said.
Jardiance can also contribute to a slight reduction in blood pressure, according to Meece.
According to the FDA, Jardiance has been studied as a stand-alone therapy and in combination with other Type 2 diabetes drugs, including metformin, sulfonylureas, pioglitazone, and insulin. The FDA states in a press release that Jardiance should not be used to treat people with Type 1 diabetes; for those who have diabetic ketoacidosis; or for those with severe renal impairment, end stage renal disease, or for patients on dialysis.
The FDA is requiring four post-marketing studies for Jardiance:
- an ongoing cardiovascular outcomes trial
- a study of how the drug works in the bodies of children and teens
- a pediatric safety and efficacy study
- and a nonclinical (animal) juvenile toxicity study with a focus on renal development, bone development, and growth
According to the FDA, Jardiance can cause dehydration, leading to a drop in blood pressure (hypotension) that can result in dizziness or fainting, and a decline in renal function. The elderly, patients with impaired kidney function, and patients taking diuretics to treat other conditions appeared to be more susceptible to this side effect.
The most common side effects of Jardiance are urinary tract infections and female genital infections, especially in those who are prone to these infections.
“If you leak urine, which is mostly going to happen in older people, when that urine dries, you are going to leave sugar on the skin. In the pelvic area, where it is moist, it is a setup for fungal and bacterial infections,” Bernstein said. “I always advise the drug companies to institute programs of hygiene so that people understand what they need to do and make sure there is no glucose deposited on the skin. They can use a wash and dry, or a washcloth with water, at least a couple times a day. The glucose is totally soluble so all of it will go away.”
Meece thinks that despite these side effects, the new drug will be embraced. “It’s an effective drug. This could well be a second drug eventually added on to metformin, as a one-two punch,” he said. “I think you will see more of that used.”
Bernstein agreed that the new drug has benefits. “You are not only lowering the blood sugar; in Type 2 that does two things. It actually increases the sensitivity of the insulin to the beta cells, because as the sugar comes back towards normal, the beta cell, within its genetic capability, functions better,” he said. “You are putting out about 250 calories a day, so you are losing weight at a very slow pace, which is best for the body, so the body adapts and doesn’t get into trouble. It’s turning out to be an advantageous drug.”
In related news, the FDA has also cleared Regeneron Pharmaceuticals’ Eylea (aflibercept) injection to treat diabetic macular edema (DME). Eylea is a vascular endothelial growth factor (VEGF) inhibitor.
DME, or “swelling of the macula,” is a common eye condition for patients with diabetes. It is the most frequent cause of vision loss in patients with diabetes and can eventually lead to blindness.
DME occurs when blood vessels in the retina are damaged by chronic high blood sugar levels caused by diabetes. This allows fluid from blood vessels to leak into the retina, causing macular swelling. The macula is the part of the retina responsible for central, fine vision.
Dr. George D. Yancopoulos, chief scientific officer of Regeneron and president of Regeneron Laboratories, said in a press statement, “Diabetic macular edema is a leading cause of vision loss among working-age adults in the United States, and we are pleased to be able to offer a new treatment option to these patients.Our clinical studies have demonstrated that treatment with Eylea can help improve and maintain vision with every eight-week dosing after five initial monthly doses. Eylea is the first VEGF inhibitor approved for dosing on a less than monthly basis for the treatment of DME.”