FDA Approves Rybelsus (semaglutide), the First Oral GLP-1 Analog Treatment for Adults with Type 2 Diabetes

In continuation of my updates on Semaglutide

Novo Nordisk today announced that the U.S. Food and Drug Administration (FDA) has approved Rybelsus (semaglutide) tablets 7 mg or 14 mg for adults with type 2 diabetes that along with diet and exercise may improve blood sugar (glucose).  Rybelsus is the first and only glucagon-like peptide-1 (GLP-1) analog in a pill and a new option for adults with type 2 diabetes who are not achieving their A1C goal with current antidiabetic treatment.

Type 2 diabetes is a global public health issue that impacts more than 28 million people in the U.S. alone.2 Despite existing treatment options, many adults with type 2 diabetes have poorly managed blood sugar that can increase the risk of developing serious diabetes-related complications.

"GLP-1 receptor agonists are effective medications for people with type 2 diabetes but have been underutilized in part because they have, until now, only been available as an injectable treatment," said Vanita R. Aroda, MD, Director of Diabetes Clinical Research, Brigham and Women's Hospital, Boston, MA and a PIONEER clinical trial investigator. "The availability of an oral GLP-1 receptor agonist represents a significant development and primary care providers, specialists and patients alike may now be more receptive to the use of a GLP-1 therapy to help them achieve their blood sugar goals."

The approval of Rybelsus is based on results from 10 PIONEER clinical trials, which enrolled 9,543 participants and included head-to-head studies of Rybelsus vs. sitagliptin, empagliflozin and liraglutide 1.8 mg.4 In the trials, Rybelsus reduced A1C and, as a secondary endpoint, showed reductions in body weight. The most common adverse reactions in the PIONEER trials, reported in ≥5% of patients, were nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation. The types and frequency of the adverse reactions were similar across trials.

"People living with type 2 diabetes deserve more innovation, research and support to help them achieve their individual A1C goals," said Todd Hobbs, vice president and U.S. chief medical officer of Novo Nordisk. "With Rybelsus, we have the opportunity to expand use of effective GLP-1 receptor agonist therapy by providing adults with type 2 diabetes an oral medication which was previously only available as an injection to help with managing their blood sugar."

Rybelsus is approved for once-daily use in two therapeutic doses, 7 mg and 14 mg, and will be available in the U.S. beginning in Q4 2019. Initial supply of Rybelsus will come from manufacturing facilities in Denmark; however, future supply for Rybelsus will come from manufacturing facilities in the U.S. In 2015, Novo Nordisk made a strategic investment to build a new manufacturing facility in Clayton, NC to prepare for the future demand for Rybelsus. Additionally, earlier this year Novo Nordisk acquired a tableting and packaging facility in Durham, NC to meet anticipated supply needs for Rybelsus.

Novo Nordisk is working with health insurance providers with a goal of ensuring broad insurance coverage and patient access to the product. A savings card program will be available at the time of launch for eligible commercially-insured patients to keep out of pocket costs down to as little as $10 a month.

The U.S. FDA is still reviewing Novo Nordisk's new drug application (NDA) for Rybelsus seeking an additional indication to reduce the risk of major adverse cardiovascular events (MACE) such as heart attack, stroke, or cardiovascular death in adults with type 2 diabetes and established cardiovascular disease (CVD). A decision is expected in Q1 2020.

Rybelsus is currently under review by several regulatory agencies around the world, including the European Medicines Agency and the Japanese Pharmaceuticals and Medical Devices Agency.

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

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

Semaglutide found to be effective against type 2 diabetes

In continuation of my update on Semaglutide

Semaglutide is safe and effective for the treatment of type 2 diabetes, according to a review published online May 13 in Diabetes, Obesity and Metabolism.

Panagiotis Andreadis, M.D., from the Aristotle University of Thessaloniki in Greece, and colleagues conducted a systematic literature review to identify randomized controlled trials comparing semaglutide with placebo or other antidiabetic agents. The primary outcome was measured change in HbA1c from baseline.

Six placebo-controlled and seven active-controlled studies were identified. The researchers found that subcutaneous semaglutide (0.5 and 1 mg) reduced HbA1c by 1.01 percent (95 percent confidence interval [CI], 0.56 to 1.47) and 1.38 percent (95 percent CI, 1.05 to 1.70), respectively, compared to placebo. Compared to other antidiabetic agents (sitagliptin, exenatide, liraglutide, dulaglutide, and insulin glargine), both doses of semaglutide demonstrated superior glycemic efficacy. There was a beneficial effect on body weight (mean difference versus placebo −4.11 kg; 95 percent CI, −4.85 to −3.37 for semaglutide 1 mg) and systolic blood pressure with semaglutide. There was increased incidence of nausea, vomiting, and diarrhea with semaglutide. Compared to placebo, the odds ratio for diabetic retinopathy was 1.32 (95 percent CI, 0.98 to 1.77).

"Semaglutide is a potent once-weekly glucagon-like peptide 1 receptor agonist, reducing significantly HbA1c, body weight, and systolic blood pressure. However, it is associated with increased incidence of gastrointestinal adverse events," the authors write.

Several authors disclosed financial ties to pharmaceutical companies, including Novo Nordisk, the manufacturer of semaglutide.

Ref : https://onlinelibrary.wiley.com/doi/10.1111/dom.13361

New diabetes drug may help people with obesity lose weight

In continuation of my update on semaglutide

A compound that mimics a naturally occurring hormone that regulates appetite may help people who have obesity but not diabetes to lose weight, a new study suggests. The research will be presented Sunday, March 18, at ENDO 2018, the Endocrine Society's 100th annual meeting in Chicago, Ill

The compound, semaglutide, has a chemical structure that is very similar to the hormone glucagon-like peptide 1 (GLP-1), which regulates both insulin secretion and appetite. In December, the U.S. Food and Drug Administration approved the semaglutide injection Ozempic as a once-weekly adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

"This randomized study of weight loss induced with semaglutide in people with obesity but without diabetes has shown the highest weight reductions yet seen for any pharmaceutical intervention," said lead author Patrick M. O'Neil, Ph.D., Director of the Weight Management Center and Professor of Psychiatry and Behavioral Sciences at the Medical University of South Carolina in Charleston, S.C.

The new study included 957 participants, 35 percent of whom were male. All participants had a body mass index (BMI) of at least 30, but did not have diabetes. They were randomly assigned to seven different groups. Five groups received different doses of semaglutide (between 0.05 mg and 0.4 mg) via injection once daily; a sixth group received a placebo, and a seventh group received 3 mg of the diabetes drug liraglutide. All participants received monthly diet and exercise counseling.

After one year, all participants receiving semaglutide had lost significantly more weight than those receiving placebo. The higher the dose participants received, the greater their average weight loss. Participants who received 0.05 mg of semaglutide daily lost an average of 6.0 percent of their body weight; the 0.1 mg group lost an average of 8.6 percent; the 0.3 mg group lost an average of 11.2 percent; and those receiving a daily dose of 0.4 mg lost an average of 13.8 percent. Those receiving liraglutide lost an average of 7.8 percent of their body weight, while those in the placebo group lost only 2.3 percent on average.

Sixty five percent of participants who received 0.4 mg of semaglutide per day lost at least 10 percent of their body weight, compared with 10 percent of those in the placebo group and 34 percent of the liraglutide group.

The most common adverse events in those taking semaglutide were mild/moderate nausea, as seen previously with GLP-1 receptor agonists.

https://www.endocrine.org/news-room/2018/new-diabetes-drug-may-help-people-with-obesity-lose-weight

Diabetes drug holds promise of being developed into new treatment for Alzheimer's

A drug developed for diabetes could be used to treat Alzheimer's after scientists found it "significantly reversed memory loss" in mice through a triple method of action.

The research, published in Brain Research, could bring substantial improvements in the treatment of Alzheimer's disease through the use of a drug originally created to treat type 2 diabetes.

Lead researcher Professor Christian Holscher of Lancaster University in the UK said the novel treatment "holds clear promise of being developed into a new treatment for chronic neurodegenerative disorders such as Alzheimer's disease."

Alzheimer's disease is the most common cause of dementia and the numbers are expected to rise to two million people in the UK by 2051 according to Alzheimer's Society, who part- funded the research.

Dr Doug Brown, Director of Research and Development at Alzheimer's Society, said: ""With no new treatments in nearly 15 years, we need to find new ways of tackling Alzheimer's. It's imperative that we explore whether drugs developed to treat other conditions can benefit people with Alzheimer's and other forms of dementia. This approach to research could make it much quicker to get promising new drugs to the people who need them."

Although the benefits of these 'triple agonist' drugs have so far only been found in mice, other studies with existing diabetes drugs such as liraglutide have shown real promise for people with Alzheimer's, so further development of this work is crucial."

This is the first time that a triple receptor drug has been used which acts in multiple ways to protect the brain from degeneration. It combines GLP-1, GIP and Glucagon which are all growth factors. Problems with growth factor signaling have been shown to be impaired in the brains of Alzheimer's patients.

The study used APP/PS1 mice, which are transgenic mice that express human mutated genes that cause Alzheimer's. Those genes have been found in people who have a form of Alzheimer's that can be inherited. Aged transgenic mice in the advanced stages of neurodegeneration were treated.

In a maze test, learning and memory formation were much improved by the drug which also:-

• enhanced levels of a brain growth factor which protects nerve cell functioning
• reduced the amount of amyloid plaques in the brain linked with Alzheimer's
• reduced both chronic inflammation and oxidative stress
• slowed down the rate of nerve cell loss

Professor Holscher said: "These very promising outcomes demonstrate the efficacy of these novel multiple receptor drugs that originally were developed to treat type 2 diabetes but have shown consistent neuro- protective effects in several studies."

"Clinical studies with an older version of this drug type already showed very promising results in people with Alzheimer's disease or with mood disorders"

"Here we show that a novel triple receptor drug shows promise as a potential treatment for Alzheimer's but further dose-response tests and direct comparisons with other drugs have to be conducted in order to evaluate if this new drugs is superior to previous ones."

Type 2 diabetes is a risk factor for Alzheimer's and has been implicated in the progression of the disease. Impaired insulin has been linked to cerebral degenerative processes in type 2 diabetes and Alzheimer's disease. Insulin desensitisation has also been observed in the Alzheimer's disease brain. The desensitisation could play a role in the development of neurodegenerative disorders as insulin is a growth factor with neuroprotective properties.

Ref : http://www.research.lancs.ac.uk/portal/en/publications/-(ccd64550-72ab-4d4b-9e42-986da99f7b36).html

Diabetes drug holds promise of being developed into new treatment for Alzheimer's

Liraglutide drug lowers blood sugar levels in diabetic patients taking large doses of insulin

In continuation of my update on   Liraglutide

Dr. Ildiko Lingvay, Associate Professor of Internal Medicine and Clinical Sciences at UT Southwestern Medical Center, designed the clinical trial, which looked at the effectiveness of liraglutide in patients who were taking high doses of insulin. 

"We have a growing population of obese patients who require larger and larger doses of insulin. The insulin causes them to put on more weight, which in turn means their glucose levels remain out of control. We wanted to test whether treating such patients with liraglutide would have an effect," said Dr. Lingvay.

Liraglutide, produced by Novo Nordisk, has several effects on the body: It increases insulin secretion; it reduces hunger; and it decreases glucagon secretion. Insulin and glucagon are molecules produced by the pancreas that have opposing effects, with insulin reducing blood sugar levels and glucagon increasing blood sugar levels. Insulin is secreted by beta cells in the pancreas and glucagon is secreted by alpha cells in the pancreas.

The study enrolled 71 Type 2 diabetes patients who were injecting large amounts of insulin each day, in most cases four or five shots a day. All of the patients had HbA1C levels that were 7.5 or higher (the goal for patients with diabetes is 7 or below). All of the patients were also overweight.

The patients in the study were randomly assigned to give themselves a daily injection of either a placebo or liraglutide in addition to their current therapy with a high dose of insulin. The results of the trial were clear, with the average HbA1C level of patients taking the drug dropping from 8.9 to 8, while long-term blood sugar levels were unchanged in the placebo group. The liraglutide patients also lost 4 ½ pounds on average, while the placebo group gained a small amount on average.

"This is less improvement than we normally see with liraglutide in patients who are not on insulin, but this is a huge improvement in a population that is so difficult to treat," said Dr. Lingvay.

Although the study was blinded - neither patients nor researchers knew which group a patient was assigned to - Ms. Sweat said that after a few weeks of being in the study she was sure that she had been assigned to the liraglutide group because her blood sugars were dropping dramatically.

"I thought I was doing the drug because my sugar finally went to normal," she said. "From the day I was diagnosed, my sugar was always high. After I started the study, for the first time in my life, my HbA1C went down, and I kept thinking, 'I must be taking the drug.' "

When the study ended, her physician prescribed liraglutide for her-whose attempt with other drugs were not successful."I give myself a shot every morning," the Garland woman said, adding that not only is her blood sugar level consistently better than it had been at any time before the study, but she has maintained a modest weight loss since the study began as well.

The study that Dr. Lingvay designed also looked at the mechanisms of action of liraglutide on this group of patients and the effect of the drug on the underlying disease, measuring insulin and glucagon blood levels following a meal.

The findings: Insulin production went up.

"The results were counterintuitive," said Dr. Lingvay. "One might expect that patients with such long-standing disease would have little or no residual beta-cell function and improvements would be driven through suppression of glucagon. To the contrary, we found that liraglutide exerted its hypoglycemic effect through improving insulin secretion."

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."

Diabetes drug found no better than placebo at treating nonalcoholic fatty liver disease: But randomized, double-blind clinical trial suggests better way to conduct future trials

A diabetes medication described in some studies as an effective treatment for nonalcoholic fatty liver disease (NAFLD) works no better than a placebo, report researchers at University of California San Diego School of Medicine, after conducting the first randomized, double-blind, controlled clinical trial of sitagliptin, an oral antihyperglycemic marketed by Merck & Co. under the name Januvia.

 

Januvia (sitagliptin)

Writing in the Journal of Hepatology, a multidisciplinary team headed by study senior author Rohit Loomba, MD, professor of medicine in the Division of Gastroenterology and director of the NAFLD Translational Research Unit at UC San Diego School of Medicine, found that sitagliptin was not significantly better than a placebo in reducing liver fat, as measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and other technologies.

The team included Claude Sirlin, MD, professor and vice chair (translational research) of radiology at UC San Diego School of Medicine, and Richard Ehman, MD, professor of radiology at Mayo Clinic. The labs, led by Sirlin and Ehman, invented and validated the advanced noninvasive imaging techniques applied in this study.

NAFLD is the accumulation of fat in the livers of people who drink little or no alcohol. It is the leading cause of chronic liver disease in the United States. Roughly one-quarter of Americans -- an estimated 100 million adults and children -- have NAFLD, which can progress to a more serious form called nonalcoholic steatohepatitis, which in turn can develop into cirrhosis, liver cancer and liver failure.

Currently, there are no approved, specific therapies for NAFLD. However, it is commonly associated with diabetes, which has prompted researchers to test diabetes medications, such as metformin, rosiglitazone and liraglutide, as potential treatments.

Sitagliptin is another possibility. In clinical trials conducted in patients with type 2 diabetes, sitagliptin has been shown to be effective in improving glycemic (blood sugar) control, cholesterol, lipoproteins and other health measures compared to placebo.

"But human trials of sitagliptin have been limited to date because they have lacked important tools like a placebo arm and allocation concealment (in which researchers do not know what the next treatment allocation will be, further preventing selection bias in testing)," said Loomba.

In the new study, 50 NAFLD patients with pre-diabetes or early diabetes were randomized into two groups: one received a 100 milligram oral dose of sitagliptin daily for 24 weeks, the other received a placebo. Primary outcome was assessed by changes to liver fat measured by MRI-PDFF, conducted by the Liver Imaging Group in the Department of Radiology at UC San Diego Health.

At end-of-treatment, Loomba and colleagues found no significant differences between sitagliptin and placebo across a range of measures. Neither study group experienced any adverse effects.

While the study did not support earlier findings that sitagliptin was an effective treatment for NAFLD, Loomba said it provided new evidence that clinical trials with patients at higher risk of diabetes do not necessarily need a liver biopsy to be efficiently screened for potential therapeutic agents.

"Biopsies present their own complications, such as possible pain and infection," said Loomba. "MRI-PDFF, and magnetic resonance elastography (a non-invasive imaging technique that measures the stiffness of soft tissues) proved to be accurate, quantitative, and useful over the study duration in measuring the state and progression of disease. These technologies should be further investigated in clinical trials, especially those of longer duration."

Liraglutide drug makes highly desirable foods less appealing to people

In continuation of my update on Liraglutide

Understanding the motivations that drive humans to eat is an important consideration in the development of weight loss therapies. Now a study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) helps explain how the diabetes and weight loss drug liraglutide acts on brain receptors to make enticing foods seems less desirable. The findings were recently presented at ENDO 2016, the annual meeting of the Endocrine Society, and will appear in the May issue of the journal Diabetologia.

"We know that everything that controls our body weight and metabolism is integrated by the brain," said senior author Christos S. Mantzoros, MD, Director of the Human Nutrition Unit in the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Professor of Medicine at Harvard Medical School. "This includes both internal stimuli such as hormones and stress, and external stimuli, such as the smell and appearance of enticing foods."

The Mantzoros laboratory has been studying the differences in the brain activity of individuals who are overweight and individuals of normal weight when they are exposed to desirable foods. These differences are quantified through computer-based neurocognitive testing, as well as imaging tests using fMRI (functional magnetic resonance imaging) to observe alterations in the activity of specific brain areas.

In this new work, the researchers examined the glucagon-like peptide (GLP) hormone, which is secreted by the gastrointestinal tract to regulate metabolism. They also examined the drug liraglutide, which is an analog, or mimicker, of the GLP hormone.

Liraglutide prolongs the action of GLP-1 receptors (protein molecules that respond to the GLP hormone's signal) and is known to work through the digestive tract and the pancreas. Previous animal studies had shown that GLP-1 may also act on the brain, but this had not been confirmed in humans.

Liraglutide drug makes highly desirable foods less appealing to people: Understanding the motivations that drive humans to eat is an important consideration in the development of weight loss therapies. Now a study led by researchers at Beth Israel Deaconess Medical Center helps explain how the diabetes and weight loss drug liraglutide acts on brain receptors to make enticing foods seems less desirable.

Adding liraglutide to diet and exercise plan may help people lose weight, reduce diabetes risk

In continuation of my update on liraglutide

For people with prediabetes who are overweight or obese, adding 3.0 mg of liraglutide for three years to a diet and exercise plan may lead to major health improvements, new industry-sponsored research suggests. The results will be presented Monday, April 4, at ENDO 2016, the annual meeting of the Endocrine Society, in Boston.

"Treatment with subcutaneous liraglutide 3.0 mg for three years, combined with a reduced-calorie diet and increased physical activity, can help people to not only lose weight, but also reduce the risk of Type 2 diabetes and improve cardiometabolic risk factors, which may ultimately reduce the risk of cardiovascular disease - the number one cause of death globally," said lead study author Ken Fujioka, MD, director of nutrition and metabolic research, and director for weight management at Scripps Research Institute in La Jolla, California.

"Type 2 diabetes is a major cause of death in the US. Both obesity, a chronic disease with serious health consequences, and prediabetes, typically defined as blood glucose concentrations that are higher than normal but lower than diabetes thresholds, increase the risk of developing Type 2 diabetes," Fujioka said. "For people with overweight or obesity and prediabetes, losing between 5 and 10 percent of their body weight can reduce their risk of Type 2 diabetes and other obesity-related health consequences."

Adding liraglutide to diet and exercise plan may help people lose weight, reduce diabetes risk

Diabetes drug liraglutide ineffective in patients with advanced heart failure

In continuation of my update on liraglutide

In an attempt to correct defects in the energy generation that contributes to poor pump function among heart failure patients, researchers examined whether the diabetes drug liraglutide, could improve the condition of patients with advanced heart failure. Despite improvements in blood sugar control, the therapy did not improve the clinical stability or pumping action of the heart in patients with advanced heart failure. Kenneth B. Margulies, MD, a professor of Medicine and research director for Heart Failure and Transplantation in the Perelman School of Medicine at the University of Pennsylvania, presented data from the Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT) study at the American Heart Association Scientific Sessions 2015.

Heart failure, a chronic condition in which the heart does not pump enough blood through the body, affects more than 5 million Americans.

"Abnormalities in the way the heart generates energy from fats and glucose, including resistance to the normal actions of insulin, have been shown to contribute to a patient's risk of heart failure. But no current heart failure treatments target these metabolic derangements," said Margulies, the principle investigator of the study. "Because liraglutide counters insulin resistance, and earlier pilot studies suggest that severely weakened hearts have the greatest metabolic defects and potential benefit, it seemed most appropriate test the efficacy of liraglutide in a group of patients with advanced heart failure. Unfortunately, the results were not what we had anticipated."

Diabetes drug liraglutide ineffective in patients with advanced heart failure

FDA Advisory Committee Votes 14-1 in Favor of Saxenda (liraglutide) for Obesity

In continuation of my update on Lirglutide

Novo Nordisk today announced that the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) of the Food and Drug Administration (FDA) has completed its meeting regarding the New Drug Application (NDA) for Saxenda, the intended brand name for liraglutide 3 mg, a once-daily human GLP-1 analogue for the treatment of obesity.

FDA Advisory Committee Votes 14-1 in Favor of Saxenda (liraglutide) for Obesity

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...

Liraglutide as Additional Treatment in Type 1 Diabetes

In continuation of my update on Liraglutide...

 Results of a small, observational study conducted at the University at Buffalo suggest that liraglutide (below structure) , an injectable medication used to treat type 2 diabetes, also helps type 1 diabetics on insulin achieve optimal control of their blood glucose levels.

More....

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....