Janumet XR Diabetes Pill Gains FDA Approval

FDA approves new extended release combo diabetes pill Janumet: High-sugar and high-fat diets, coupled with desk-bound lifestyles more common in today’s high-paced world are driving the rapid global rise of type 2 diabetes.

Type 2 diabetes, the kind linked more to poor diet and lack of exercise rather than to genetics, makes up 90 to 95 percent of the 300 million people now suffering from diabetes.

The mounting number of cases, as well as the complications—a higher risk for blindness, heart attacks, kidney problems, and loss of limbs—has prodded the World Health Organization to declare a diabetes epidemic.

Because their bodies don’t produce enough insulin or they’ve become resistant to the hormone, which controls blood sugar levels, people with type 2 diabetes are unable to break down carbohydrates properly.

When this happens, sugar remains in their bloodstream. To control their blood sugar, diabetes sufferers have to take many drugs that work in different ways and act on different body mechanisms. Some of these drugs have to be taken more than once daily; some are pills, others are injected.

But keeping track of these drugs—and when and how to take them—can be difficult, especially in today’s demanding and fast-paced world.

Enabling people to take their medicines consistently helps boost patient outcomes , notes David Kliff of a diabetes once-a-week injection approved recently by United States drug regulators. Kliff is publisher of Diabetic Investor, an electronic newsletter following the diabetes industry, and a diabetes survivor himself.

This is why, in recent years, drug makers have been working to make diabetes medications that can be taken less frequently.

New diabetes combo pill
A newer, more convenient version of an older diabetes medication has been recently approved by the U.S. Food and Drug Authority.

On Feb. 2, the FDA approved an extended-release version of the diabetes drug Janumet designed to be taken once a day, instead of twice a day, the drug’s maker Merck & Co Inc. said in a press release.

The agency approved Janumet XR to help patients with type 2 diabetes control their blood sugar levels, in combination with diet and exercise, the company said in a statement.

Janumet XR is a pill that combines sitagliptin, the primary ingredient in the company’s drug Januvia, with an older diabetes drug, metformin.

The new extended-release tablets targets three key defects of diabetes: insulin deficiency from pancreatic beta cells, insulin resistance, and overproduction of glucose by the liver.

Janumet XR can help many patients reach blood sugar goals, Merck said, but warned: It’s also not for use in people with type 1 diabetes or people with a diabetic ketoacidosis, caused by very high blood sugar. Diabetic ketoacidosis should be treated with insulin, the company said.

The FDA approved the new drug based on chemical studies that showed the combination pill was comparable to taking Januvia and extended release metformin separately and that extended-release metformin was as effective as immediate-release metformin.

“Janumet XR is a new treatment that adds once-daily convenience to the powerful efficacy of Janumet for patients with type 2 diabetes,” says Dr. Barry J. Goldstein, Merck’s vice president for diabetes and endocrinology, in the news release. “This is important because many patients with type 2 diabetes require treatment with multiple drugs to maintain blood sugar control, and Janumet XR is a new option to help more patients get to their glucose goals.”

The most common adverse reactions reported with the sitagliptin-metformin pill were diarrhea, upper respiratory infection and headache.

Lactic acidosis
The combination drug’s label contains a boxed warning for lactic acidosis, a rare but serious complication caused by metformin accumulation.

According to Merck, the reported incidence of lactic acidosis in patients receiving metformin is approximately 0.03 cases/1000 patient-years—but when lactic acidosis occurs, it’s fatal half of the time.

Cases have happened mainly in patients with diabetes who have significant renal impairment, but excessive alcoholic intake, liver impairment and acute congestive heart failure increase the risk for lactic acidosis.

“If acidosis is suspected, Janumet XR should be discontinued and the patient hospitalized immediately,” the company added.

Renal functions
Merck also advised doctors to assess and verify their patients’ renal functions before starting therapy with Janumet XR and check these at least once a year while the new diabetes drug is being used in therapy.

“There have been postmarketing reports of worsening renal function in patients taking sitagliptin with or without metformin, including acute renal failure, sometimes requiring dialysis,” it warned. “Janumet XR treatment should not be initiated in any patient unless measurement of creatinine clearance demonstrates that renal function isn’t reduced.”

The renal function of eldery patients being treated with Janumet XR should be carefully monitored, the company also said.

In addition, the new sitagliptin-metformin pill should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis, Merck said.

Merck also said don’t take Janumet XR if you:

• Have renal impairment (e.g., serum creatinine levels greater-than or equal to 1.5 mg/dL for men, greater-than or equal to 1.4 mg/dL for women or abnormal creatinine clearance), which may also result from cardiovascular collapse (shock), acute myocardial infarction, and septicemia.
• Are hypersensitive to metformin HCl.
• Have acute or chronic metabolic acidosis, including diabetic ketoacidosis
• Have a history of a serious hypersensitivity reaction to JANUMET XR or sitagliptin, such as anaphylaxis or angioedema.

According to Merck, there have been post-marketing reports of serious hypersensitivity reactions in patients treated with sitagliptin, one of the components of Janumet XR. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome—occurring mostly within the first three months after starting sitagliptin, although with some cases happening immediately, after the first dose.

It’s also unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using Janumet XR, the drugmaker warned.

But on September 2009, the FDA ordered Merck to revise prescribing information over the drug’s earlier, version, Janumet (sitagliptin/metformin), to include information on reported cases of acute pancreatitis in patients using these products.

The agency said 88 post-marketing cases of acute pancreatitis, including two cases of hemorrhagic or necrotizing pancreatitis in patients using sitagliptin, were reported to the agency between October 16, 2006 and February 9, 2009.

Janumet XR is available in tablets of 100 mg sitagliptin/1000 mg metformin HCl extended-release, 50 mg sitagliptin/500 mg metformin HCl extended-release, and 50 mg sitagliptin/1000 mg metformin HCl extended-release.

Doctors can individualize the dose of Janumet XR, based on the patient’s current regimen, effectiveness, and tolerability, for as long as the maximum recommended daily dose of 100 mg sitagliptin and 2000 mg metformin isn’t exceeded.

When changing between Janumet and Janumet XR, doctors are advised to maintain the same total daily dose of sitagliptin and metformin and to titrate the dose up gradually to the maximum recommended dose to reduce adverse gastrointestinal effects.

Janumet XR should be taken once daily with food)—preferably in the evening)—to reduce the gastrointestinal adverse effects associated with the metformin component.

The tablets must not be split, broken, crushed, or chewed before swallowing, the company said.