FDA Approves Victoza (liraglutide) for the Treatment of Pediatric Patients 10 Years or Older with Type 2 Diabetes

In continuation of my update on Victoza (liraglutide)

The U.S. Food and Drug Administration   approved Victoza (liraglutide) injection for treatment of pediatric patients 10 years or older with type 2 diabetes. Victoza is the first non-insulin drug approved to treat type 2 diabetes in pediatric patients since metformin was approved for pediatric use in 2000. Victoza has been approved to treat adult patients with type 2 diabetes since 2010.

“The FDA encourages drugs to be made available to the widest number of patients possible when there is evidence of safety and efficacy,” said Lisa Yanoff, M.D, acting director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research. “Victoza has now been shown to improve blood sugar control in pediatric patients with type 2 diabetes. The expanded indication provides an additional treatment option at a time when an increasing number of children are being diagnosed with this disease.”

Type 2 diabetes is the most common form of diabetes, occurring when the pancreas cannot make enough insulin to keep blood sugar at normal levels. Although type 2 diabetes primarily occurs in patients over the age of 45, the prevalence rate among younger patients has been rising dramatically over the past couple of decades. The Diabetes Report Card published by the U.S. Centers for Disease Control and Prevention estimates that more than 5,000 new cases of type 2 diabetes are diagnosed each year among U.S. youth younger than age 20.

Victoza improves blood sugar levels by creating the same effects in the body as the glucagon-like peptide (GLP-1) receptor protein in the pancreas. GLP-1 is often found in insufficient levels in type 2 diabetes patients. Like GLP-1, Victoza slows digestion, prevents the liver from making too much glucose (a simple sugar), and helps the pancreas produce more insulin when needed. As noted on the label, Victoza is not a substitute for insulin and is not indicated for patients with type 1 diabetes or those with diabetic ketoacidosis, a condition associated with diabetes where the body breaks down fat too quickly because there is inadequate insulin or none at all. Victoza is also indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease; however, its effect on major adverse cardiovascular events in pediatrics was not studied and it is not indicated for this use in children.

The efficacy and safety of Victoza for reducing blood sugar in patients with type 2 diabetes was studied in several placebo-controlled trials in adults and one placebo-controlled trial with 134 pediatric patients 10 years and older for more than 26 weeks. Approximately 64% of patients in the pediatric study had a reduction in their hemoglobin A1c (HbA1c) below 7% while on Victoza, compared to only 37% who achieved these results with the placebo. HbA1c is a blood test that is routinely performed to evaluate how well a patient’s diabetes is controlled, and a lower number indicates better control of the disease. These results occurred regardless of whether the patient also took insulin at the same time. Adult patients who took Victoza with insulin or other drugs that increase the amount of insulin the body makes (e.g., sulfonylurea) may have an increased risk of hypoglycemia (low blood sugar). Meanwhile, pediatric patients 10 years and older taking Victoza had a higher risk of hypoglycemia regardless of whether they took other therapies for diabetes.

The prescribing information for Victoza includes a Boxed Warning to advise health care professionals and patients about the increased risk of thyroid C-cell tumors. For this reason, patients who have had, or have family members who have ever had medullary thyroid carcinoma (MTC) should not use Victoza, nor should patients who have an endocrine system condition called multiple endocrine neoplasia syndrome type 2 (MEN 2). In addition, people who have a prior serious hypersensitivity reaction to Victoza or any of the product components should not use Victoza. Victoza also carries warnings about pancreatitis, Victoza pen sharing, hypoglycemia when used in conjunction with certain other drugs known to cause hypoglycemia including insulin and sulfonylurea, renal impairment or kidney failure, hypersensitivity and acute gallbladder disease. The most common side effects are nausea, diarrhea, vomiting, decreased appetite, indigestion and constipation.

https://en.wikipedia.org/wiki/Liraglutide

This Diabetes Drug Saves Lives. You Can Thank The FDA

Researchers are announcing that Victoza, a diabetes drug sold by Danish drug giant Novo Nordisk , prevents heart attacks, strokes and cardiovascular deaths.

 liraglutide-Victoza

It is only the second diabetes drug ever to do so. The first, Jardiance, a pill sold by Eli Lilly LLY -0.91% and Boehringer Ingelheim , presented its positive results just last year. Researchers say that the new results could change the way that doctors treat diabetes, shifting the treatments doctors reach for after metformin, the tried-and-true first-line drug, which is generic. “There’s a building momentum that maybe we do need to rethink the way diabetes is cared for in America,” says John Buse, the University of North Carolina, Chapel Hill researcher who led the study, which was funded by Novo Nordisk.

And doctors and Novo Nordisk itself give credit to the new diabetes data to a surprising source: Tougher regulations for diabetes drugs from the Food and Drug Administration, which many in industry had previously decried, saying it was keeping new drugs from the market and hurting patients. “I can almost guarantee you that these trials would not have been done if it had not been for the FDA regulations,” says Buse, who has been a consultant to many companies for years. “Before the guidance I was constantly pushing on companies to do these trials.”

That fact–that companies and patients are likely to benefit from the FDA’s toughness–goes against one of the common narratives in the drug industry and among the FDA’s critics: that high regulations slow patients’ access. In some cases, it’s clear, they also create a bar for industry to leap over, and deliver billions of dollars in spoils to companies that actually manage to help patients, not just blood test results.

The Victoza result is exactly the kind of marketing claim that makes a drug company salivate: Novo Nordisk can now tell patients and their insurers that the alternative to its drug is an earlier death.

In the study, presented this evening at the annual meeting of the American Diabetes Association and published in the New England Journal of Medicine, 9,340 patients were randomly assigned to receive either Victoza or placebo for a median of 3.8 years. For those on Victoza, 13% had a heart attack, stroke or death, compared to 14.9% on placebo, a 13% decrease in risk. Reductions in cardiovascular death (22%) and death from any cause (15%) were also statistically significant. A supposed side effect of the drug, pancreatitis, did not show up at all, and patients on Victoza lost 2.3 kilograms (about 5 pounds) more than those on placebo.

Diet Drugs: Which Ones Work?

Any of the prescription weight-loss drugs on the market can help obese people shed pounds, although some seem more effective than others, a new study finds.

Currently, five drugs are approved in the United States for managing obesity. But little has been known about how they stack up against one another, said Dr. Siddharth Singh, the lead researcher on the new study.

The findings  based on more than 29,000 people in total show all five drugs can work. But people on certain drugs tended to be more successful, at least over one year.

Specifically, people using Qsymia (phentermine-topiramate) or Victoza (liraglutide) had the highest odds of shedding at least 5 percent of their initial weight. Those taking Xenical (orlistat) had the lowest odds.

phentermine liraglutide

 orlistat  lorcaserin

 Bupropion/naltrexone 

However, there is no single drug that's "best" for everyone, stressed Singh, an assistant clinical professor at the University of California, San Diego.

He cautioned that his team's numbers are just averages across study groups. Plus, he said, the side effects of each medication vary, and that is an important factor in treatment decisions.

"Obesity treatment always needs to be personalized," Singh said.

Nikhil Dhurandhar, a spokesman for the Obesity Society, agreed that people respond differently to any given weight-loss drug.

"In general, if you give drug 'X,' there will be a wide variation in patients' responses," said Dhurandhar, who is also a professor of nutritional sciences at Texas Tech University in Lubbock. He wasn't involved in the study.

Some people will have "zero" weight loss   or even gain weight -- while others will see the pounds drop off, Dhurandhar said.

He also stressed that there is no such thing as a magic weight-loss pill.

"These drugs can help you eat less through effects on appetite," Dhurandhar explained. "But you have to change your diet and get regular exercise."

"Medications are supplements, not substitutes, to your efforts," he said.

For the study, Singh's team analyzed findings from 28 clinical trials testing the five approved drugs for obesity: Qsymia, Victoza and Xenical, along with Belviq (lorcaserin) and Contrave (naltrexone-bupropion).

On average, the researchers found, each drug worked better than a placebo in helping obese adults lose weight over a year. But certain medications seemed more effective than others.

People on Qsymia typically lost the most weight -- almost 20 pounds more, versus study patients given placebo pills. They were also nine times more likely to drop at least 5 percent of their initial weight, the researchers found.

People taking Xenical or Belviq tended to shed the fewest pounds -- 6 to 7 pounds more than placebo users. Contrave and Victoza patients typically lost 11 to 12 pounds more, compared with placebo.

But not everyone benefited. In studies of all of the drugs, Singh noted, a significant number of people dropped out because of side effects.

And those dropouts were more common with certain medications, the study found. People taking Contrave or Victoza were almost three times more likely to quit a trial over side effects, compared with placebo users. According to Victoza's maker, the drug can cause inflammation of the pancreas or kidney problems.

Just as people vary in their weight-loss success with any given drug, their risks of side effects will differ, too, Singh said.

He pointed to Contrave as an example. Because it contains the antidepressant bupropion, it carries a boxed warning about the potential risk of suicidal thoughts. So it might not be the best choice for someone with psychiatric conditions that could make them more vulnerable, Singh said.

Victoza, meanwhile, is an injection drug prescribed for controlling high blood sugar in people with type 2 diabetes. So if a patient needs medication for diabetes as well as weight loss, Victoza might be a good option, Singh said.

Most of the medications have been approved only in the past few years, so one question is whether they maintain their effects over the long run, Singh said.

"We do need more long-term data," Dhurandhar agreed.

Still, he said, medications are an important option for managing obesity. And if one does not work, Dhurandhar added, he'd recommend trying another.

Diabetes Drug Victoza May Help the Heart: Study

In continuation of my update on liraglutide

The blood sugar-lowering drug Victoza (liraglutide) cuts the risk of heart attack and stroke in type 2 diabetes patients, a new study finds.

Heart disease is the leading cause of death among people with type 2 diabetes, the researchers noted.

The study was funded by the drug's maker, Novo Nordisk, and the U.S. National Institutes of Health. It included more than 9,300 adults from 32 countries who have type 2 diabetes and a high risk of heart disease.

About half took Victoza, while the other half took an inactive placebo. Both groups also took other medications for health problems, such as high blood pressure and high cholesterol, the study authors said.

Tracking patients for three years, the researchers found that compared with patients in the placebo group, people who took Victoza had a 13 percent lower risk of heart attack or stroke. They also had a 22 percent lower risk of death from heart disease; a 15 percent lower risk of death from any cause; and a 22 percent lower risk of new evidence of advanced kidney disease.

Some patients did discontinue the drug due to "gastrointestinal events," according to the report.

The study was presented June 13 at the American Diabetes Association's annual meeting, in New Orleans. It was also published simultaneously in the New England Journal of Medicine.

"I've been excited about liraglutide for a long time because I think it's unique," said study senior author Dr. John Buse. He directs the Diabetes Care Center at the University of North Carolina, Chapel Hill.

"This is the first diabetes drug that has shown across-the-board benefits for cardiovascular diseases, and this suggests it plays a role in treating atherosclerosis [hardening of the arteries], which is what leads to heart attacks and strokes," Buse said in a university news release.

One diabetes expert called the study "encouraging."

Victoza "is a relatively new medication, given by daily injection," said Dr. Allison Reiss, who runs the inflammation laboratory at Winthrop-University Hospital in Mineola, N.Y.

Still, the long-term effectiveness of the drug is unknown, Reiss added. "It will be important to follow these patients over the next few years to see whether [Victoza] benefits continue and to investigate how it is working," she said.

The researchers explained that Victoza is from a newer class of diabetes drugs known as GLP-1 agonists. These medications work in the pancreas to cut the production of an anti-insulin hormone called glucagon. The drugs boost insulin production and help control blood sugar levels.

As a secondary mechanism, Victoza also works on the brain to help lower appetite and boost feelings of "fullness" when eating, Buse's team explained.

Reiss noted that because of this activity, Victoza can help spur weight loss -- and that might be the prime factor driving the improvements in heart health.

Dr. Gerald Bernstein coordinates the Friedman Diabetes Program at Lenox Hill Hospital in New York City. He said that Victoza -- and other drugs in its class -- are being increasingly used, so "decreased cardiovascular risk is an important finding."

Victoza Label Updated to Include Data Showing Superior Efficacy When Compared to Januvia

 In continuation of my update on Liraglutide

Victoza Label Updated to Include Data Showing Superior Efficacy When Compared to Januvia:  Novo Nordisk received approval from the U.S. Food and Drug Administration (FDA) to update the product label for Victoza (liraglutide [rDNA origin] injection) to include data showing superior blood...

FDA approves Liraglutide for Type 2 Diabetes, with a warning.....

Liraglutide, marketed under the brand name Victoza, is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been developed by Novo Nordisk for the treatment of type 2 diabetes. The product was approved by the European Medicines Agency (EMEA) on July 3, 2009, Now the same drug has been approved  by the FDA.

The interesting part of this approval lies in the fact that, Liraglutide was reviewed by an FDA advisory panel which expressed serious concerns that the drug may cause thyroid tumors. Whereas based on the studies and consistent with the relevant literature it is obvious that the rodent C-cell tumors induced by dosing of liraglutide were caused by a non-genotoxic, specific receptormediated mechanism to which rodents are particularly sensitive whereas non-human primates and humans are not. Liraglutide improves control of blood glucose.  It reduces meal-related hyperglycaemia (for 12 hours after administration) by increasing insulin secretion, delaying gastric emptying, and suppressing prandial glucagon secretion.

As per the claim by the company, the advantages are:

a) acts in a glucose-dependent manner, and  stimulate insulin secretion only when blood glucose levels are

    higher than normal. Consequently, it shows negligible risk of hypoglycemia;

b) has the potential for inhibiting apoptosis and stimulating regeneration of beta cells;

c) decreases appetite and maintains body weight, as shown in a head-to-head study versus glimepiride;

d) lowers blood triglyceride levels and only mild and transient side effects, mainly gastrointestinal &
e) has a half-life after subcutaneous injection of 11–15 hours and hence once-daily GLP-1 derivative.

But the FDA, warned that the once-daily injection shouldn't be used as an initial (first-line) treatment until additional studies are completed, since the drug may cause thyroid tumors or a rare disease called medullary thyroid cancer. People at risk for this type of cancer shouldn't use the drug, the FDA stressed. Hope the further studies will rule out the possibility of the drug causing thyroid tumors..

For details, one can read the press release....