New FDA approval: semaglutide, the first oral GLP-1 agonist for type 2 diabetes

The FDA has now approved the first oral semaglutide, Rybelsus, for the treatment of type 2 diabetes. This approval marks a breakthrough advancement in the field of clinical diabetology. Rybelsus is the first "protein" based molecule to be administered orally and not subcutaneously via an injection.

Oral administration of semaglutide is made possible through the use of SNAC compound. SNAC helps escort and transport the semaglutide intact across the gastrointestinal epithelial cells. It assists in bypassing the harsh acidic environment of the stomach.

Various clinical trials, under the name PIONEER, have consistently shown A1c improvements and weight loss benefits with Rybelsus – thus leading to this landmark FDA acceptance.

Rybelsus comes at three doses; 3, 7, and 14 milligrams. Patients should start at 3 mg per day for one month before advancing to the 7 mg, and if needed, to the 14 mg daily dosage. Rybelsus should be taken in an empty stomach, with no more than 4 ounces of plain water, and at least 30 minutes before breakfast.

Similar to other GLP-1 agonists, oral semaglutide can cause gastrointestinal side effects like nausea and diarrhea. Providers should be cautious when prescribing Rybelsus in those with a predisposed risk for pancreatitis, diabetic retinopathy, or kidney injury. It should not be prescribed in people with a personal or family history of medullary thyroid carcinoma.

GT

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Semaglutide

Diabetes

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FDA APPROVAL 

DRUG THERAPY

September 2019

The U.S. Food and Drug Administration today approved Rybelsus (semaglutide) oral tablets to improve control of blood sugar in adult patients with type 2 diabetes, along with diet and exercise. Rybelsus is the first glucagon-like peptide (GLP-1) receptor protein treatment approved for use in the United States that does not need to be injected. GLP-1 drugs are non-insulin treatments for people with type 2 diabetes.

“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,” 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. “Before this approval, patients did not have an oral GLP1 option to treat their type 2 diabetes, and now patients will have a new option for treating type 2 diabetes without injections.”

  • 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. GLP-1, which is a normal body hormone, is often found in insufficient levels in type 2 diabetes patients. Like GLP-1, Rybelsus slows digestion, prevents the liver from making too much sugar, and helps the pancreas produce more insulin when needed.

The efficacy and safety of Rybelsus in reducing blood sugar in patients with type 2 diabetes were studied in several clinical trials, two of which were placebo-controlled and several of which were compared to other GLP-1 injection treatments. Rybelsus was studied as a stand-alone therapy and in combination with other diabetes treatments, including metformin, sulfonylureas (insulin secretagogues), sodium-glucose co-transporter-2 (SGLT-2) inhibitors, insulins and thiazolidinediones, all in patients with type 2 diabetes.

In the placebo-controlled studies, Rybelsus as a stand-alone therapy resulted in a significant reduction in blood sugar (hemoglobin A1c) compared with placebo, as determined through HbA1c tests, which measure average levels of blood sugar over time. After 26 weeks, 69% of those taking 7 mg once daily and 77% of those taking 14 mg once daily of Rybelsus decreased their HbA1c to lower than 7%, compared with 31% of patients on placebo.

The prescribing information for Rybelsus includes a boxed warning to advise health care professionals and patients about the potential increased risk of thyroid c-cell tumors, and that Rybelsus is not recommended as the first choice of medicine for treating diabetes.

  • Patients who have ever had medullary thyroid carcinoma (MTC) or who have a family member who has ever had MTC are advised not to use Rybelsus.

  • Additionally, patients who have ever had an endocrine system condition called multiple endocrine neoplasia syndrome type 2 (MEN 2) are advised not to use Rybelsus.

  • Rybelsus is not for use in patients with type 1 diabetes and people with diabetic ketoacidosis.

Rybelsus also has warnings about pancreatitis (inflammation of the pancreas), diabetic retinopathy (damage to the eye’s retina), hypoglycemia (low blood sugar), acute kidney injury and hypersensitivity reactions.

  • It is not known whether Rybelsus can be used by patients who have had pancreatitis.

  • The risk of hypoglycemia increased when Rybelsus was used in combination with sulfonylureas or insulin.

Rybelsus should be taken at least 30 minutes before the first food, beverage or other oral medication of the day, with no more than 4 ounces of plain water. Rybelsus slows digestion, so patients should discuss other medications they are taking with their health care provider before starting Rybelsus.

  • The most common side effects are nausea, diarrhea, vomiting, decreased appetite, indigestion and constipation.


Dosage and Administration:

Instruct patients to take Rybelsus at least 30 minutes before the first food, beverage, or other oral medications of the day with no more than 4 ounces of plain water only. Waiting less than 30 minutes, or taking with food, beverages (other than plain water) or other oral medications will lessen the effect of Rybelsus. Waiting more than 30 minutes to eat may increase the absorption of Rybelsus.

  • Swallow tablets whole. Do not cut, crush, or chew tablets.

  • Start Rybelsus with 3 mg once daily for 30 days. After 30 days on the 3 mg dose, increase the dose to 7 mg once daily.

  • Dose may be increased to 14 mg once daily if additional glycemic control is needed after at least 30 days on the 7 mg dose.

Warnings and Precautions:

  • Pancreatitis: Has been reported in clinical trials. Discontinue promptly if pancreatitis is suspected. Do not restart if pancreatitis is confirmed.

  • Diabetic Retinopathy Complications: Has been reported in a cardiovascular outcomes trial with semaglutide injection. Patients with a history of diabetic retinopathy should be monitored.

  • Hypoglycemia: When Rybelsus is used with an insulin secretagogue or insulin, consider lowering the dose of the secretagogue or insulin to reduce the risk of hypoglycemia.

  • Acute Kidney Injury: Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions.

  • Hypersensitivity Reactions: Discontinue Rybelsus if suspected and promptly seek medical advice.