FDA NewsPerspective

FDA approves first oral GLP-1 receptor agonist for diabetes

The FDA on Friday approved oral semaglutide, the first noninjectable GLP-1 receptor agonist for the treatment of type 2 diabetes, according to an agency press release.

The approval follows several large trials for oral semaglutide (Rybelsus, Novo Nordisk) that demonstrated the therapy was associated with superior HbA1c reductions vs. placebo (PIONEER 4), vs. the oral SGLT2 inhibitor empagliflozin (PIONEER 2; Jardiance, Boehringer Ingelheim) and vs. the oral DPP-IV inhibitor sitagliptin (PIONEER 3; Januvia, Merck). Oral semaglutide also provided significant weight loss at 52 weeks for participants with type 2 diabetes uncontrolled with metformin therapy.

“Patients want effective treatment options for diabetes that are as minimally intrusive on their lives as possible, and the FDA welcomes the advancement of new therapeutic options that can make it easier for patients to control their condition,” Lisa Yanoff, MD, acting director of the division of metabolism and endocrinology products in the FDA’s Center for Drug Evaluation and Research, said in the release. “Before this approval, patients did not have an oral GLP-1 option to treat their type 2 diabetes, and now patients will have a new option for treating type 2 diabetes without injections.”

In PIONEER 2, participants assigned oral semaglutide experienced a greater reduction in HbA1c vs. empagliflozin at 26 weeks (treatment policy mean reduction, –1.3%; trial product mean reduction, –0.9%; P < .0001), with similar results at 52 weeks, according to findings reported at the American Diabetes Association Scientific Sessions in June. In PIONEER 4, At 26 weeks, researchers observed similar reductions in HbA1c in the semaglutide group vs. the liraglutide group for noninferiority of semaglutide to liraglutide.

 
The FDA on Friday approved oral semaglutide, the first noninjectable GLP-1 receptor agonist for the treatment of type 2 diabetes.
Source: Shutterstock

In the placebo-controlled studies, 69% of patients assigned to 7 mg oral semaglutide and 77% of patients assigned to 14 mg oral semaglutide decreased their HbA1c to 7% or lower at 26 weeks, compared with 31% of patients assigned placebo, according to the FDA.

In a press release from Novo Nordisk announcing the approval, Vanita R. Aroda, MD, director of diabetes clinical research at Brigham and Women's Hospital in Boston and a PIONEER clinical trial investigator, said GLP-1 receptor agonists are effective medications for people with type 2 diabetes that have been underutilized.

“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,” Aroda said in the release.

The prescribing information for oral semaglutide includes a boxed warning to advise health care professionals and patients that semaglutide may present an increased risk for thyroid C-cell tumors, and that semaglutide is not recommended as the first choice of medicine for treating diabetes. Oral semaglutide is also contraindicated for individuals who have had medullary thyroid carcinoma or a family member who has ever had medullary thyroid carcinoma; adults who have had multiple endocrine neoplasia syndrome type 2; those with type 1 diabetes; and people with diabetic ketoacidosis.

Oral semaglutide also has warnings about pancreatitis, diabetic retinopathy, hypoglycemia, acute kidney injury and hypersensitivity reactions.

Oral semaglutide should be taken at least 30 minutes before the first food, beverage or other oral medication of the day with no more than 4 oz plain water. The most common adverse effects are nausea, diarrhea, vomiting, decreased appetite, indigestion and constipation.

In its release, Novo Nordisk said it is working with health insurance providers to ensure 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.

The FDA is still reviewing Novo Nordisk’s new drug application for oral semaglutide seeking an additional indication to reduce the risk for major adverse cardiovascular events in adults with type 2 diabetes and established CVD. A decision is expected in the first quarter of 2020, according to the company.

The European Medicines Agency and the Japanese Pharmaceuticals and Medical Devices Agency are also reviewing the drug. – by Regina Schaffer

Disclosure: Yanoff is acting director of the division of metabolism and endocrinology products in the FDA’s Center for Drug Evaluation and Research.

The FDA on Friday approved oral semaglutide, the first noninjectable GLP-1 receptor agonist for the treatment of type 2 diabetes, according to an agency press release.

The approval follows several large trials for oral semaglutide (Rybelsus, Novo Nordisk) that demonstrated the therapy was associated with superior HbA1c reductions vs. placebo (PIONEER 4), vs. the oral SGLT2 inhibitor empagliflozin (PIONEER 2; Jardiance, Boehringer Ingelheim) and vs. the oral DPP-IV inhibitor sitagliptin (PIONEER 3; Januvia, Merck). Oral semaglutide also provided significant weight loss at 52 weeks for participants with type 2 diabetes uncontrolled with metformin therapy.

“Patients want effective treatment options for diabetes that are as minimally intrusive on their lives as possible, and the FDA welcomes the advancement of new therapeutic options that can make it easier for patients to control their condition,” Lisa Yanoff, MD, acting director of the division of metabolism and endocrinology products in the FDA’s Center for Drug Evaluation and Research, said in the release. “Before this approval, patients did not have an oral GLP-1 option to treat their type 2 diabetes, and now patients will have a new option for treating type 2 diabetes without injections.”

In PIONEER 2, participants assigned oral semaglutide experienced a greater reduction in HbA1c vs. empagliflozin at 26 weeks (treatment policy mean reduction, –1.3%; trial product mean reduction, –0.9%; P < .0001), with similar results at 52 weeks, according to findings reported at the American Diabetes Association Scientific Sessions in June. In PIONEER 4, At 26 weeks, researchers observed similar reductions in HbA1c in the semaglutide group vs. the liraglutide group for noninferiority of semaglutide to liraglutide.

 
The FDA on Friday approved oral semaglutide, the first noninjectable GLP-1 receptor agonist for the treatment of type 2 diabetes.
Source: Shutterstock

In the placebo-controlled studies, 69% of patients assigned to 7 mg oral semaglutide and 77% of patients assigned to 14 mg oral semaglutide decreased their HbA1c to 7% or lower at 26 weeks, compared with 31% of patients assigned placebo, according to the FDA.

In a press release from Novo Nordisk announcing the approval, Vanita R. Aroda, MD, director of diabetes clinical research at Brigham and Women's Hospital in Boston and a PIONEER clinical trial investigator, said GLP-1 receptor agonists are effective medications for people with type 2 diabetes that have been underutilized.

“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,” Aroda said in the release.

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The prescribing information for oral semaglutide includes a boxed warning to advise health care professionals and patients that semaglutide may present an increased risk for thyroid C-cell tumors, and that semaglutide is not recommended as the first choice of medicine for treating diabetes. Oral semaglutide is also contraindicated for individuals who have had medullary thyroid carcinoma or a family member who has ever had medullary thyroid carcinoma; adults who have had multiple endocrine neoplasia syndrome type 2; those with type 1 diabetes; and people with diabetic ketoacidosis.

Oral semaglutide also has warnings about pancreatitis, diabetic retinopathy, hypoglycemia, acute kidney injury and hypersensitivity reactions.

Oral semaglutide should be taken at least 30 minutes before the first food, beverage or other oral medication of the day with no more than 4 oz plain water. The most common adverse effects are nausea, diarrhea, vomiting, decreased appetite, indigestion and constipation.

In its release, Novo Nordisk said it is working with health insurance providers to ensure 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.

The FDA is still reviewing Novo Nordisk’s new drug application for oral semaglutide seeking an additional indication to reduce the risk for major adverse cardiovascular events in adults with type 2 diabetes and established CVD. A decision is expected in the first quarter of 2020, according to the company.

The European Medicines Agency and the Japanese Pharmaceuticals and Medical Devices Agency are also reviewing the drug. – by Regina Schaffer

Disclosure: Yanoff is acting director of the division of metabolism and endocrinology products in the FDA’s Center for Drug Evaluation and Research.

    Perspective
    Debra L. Simmons

    Debra L. Simmons

    It is exciting to have the first oral GLP-1 receptor agonist approved for type 2 diabetes. Many people are fine with taking an injection; however, they may prefer a pill if one is available. For this particular class to be the first with an oral agent is something that is exciting for everyone. The requirement to abstain from food or other medications for 30 minutes after taking the drug should not temper enthusiasm; most patients now understand that some medications simply require a little more effort. Compared with taking an injection, this is a more convenient option for many people with type 2 diabetes.

    • Debra L. Simmons, MD, MS, FACE, FACP
    • Professor of Medicine, University of Utah Director of Clinical Affairs
      Utah Diabetes and Endocrinology Center

    Disclosures: Simmons reports no relevant financial disclosures.

    Perspective
    George Grunberger

    George Grunberger

    Given the uniformly positive findings from phase 3 trials across the disease spectrum of type 2 diabetes, this approval does not come as a surprise. This is excellent news for all patients and prescribing health care professionals. We need as many options as possible for our patients, and the lack of hypoglycemia and absence of weight gain indeed with oral semaglutide, most patients have lost weight mean more options to hopefully improve our management and prevent the complications of uncontrolled type 2 diabetes. It remains to be seen how patients will accept the drug’s limitations ie, need for at least a 30-minute wait before any other medications can be taken and abstinence from any oral intake for that amount of time in their daily routines. However, for those needle-phobic patients, having the first-ever oral GLP-1 receptor agonist on the market is truly groundbreaking. It is unfortunate that the class warnings are still included for C-cell tumor risk, risks for pancreatitis and hypoglycemia and that the drug should not to be taken as a first line therapy, etc. To my knowledge, the C-cell hyperplasia has only been seen in rodents, and there has been no statistically significant increase of pancreatitis with oral semaglutide. The risk for hypoglycemia is due to sulfonylurea and insulin and not semaglutide. Semaglutide was effective as a monotherapy in drug-naive patients. It will be interesting to see how many of the people currently injecting semaglutide weekly would be interested in switching to a daily oral preparation vs. those who have not yet injected a GLP-1 receptor agonist.

    • George Grunberger, MD, FACP, FACE
    • Chairman, Grunberger Diabetes Institute
      Bloomfield Hills, Michigan

    Disclosures: Grunberger reports no relevant financial disclosures.