RYBELSUS® (semaglutide), the pill that delivered superior A1C reduction vs Januvia® (sitagliptin) at 26 weeks1
Wondering why RYBELSUS® should be a go-to for your appropriate patients? In a head-to-head trial, the only FDA-approved semaglutide in a pill for adult patients with type 2 diabetes delivered1:
Superior A1C reductions at 26 weeks1,2
Superior A1C control (<7%) at 26 weeks1,2
Superior reduction in body weight at 26 weeks1,2
Superior A1C reductions at 26 weeks1,2
Superior A1C control (<7%) at 26 weeks1,2
Superior reduction in body weight at 26 weeks1,2
Explore the study results below, and see information on competitive commercial coverage.a,b
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.
RYBELSUS® is not indicated for weight loss.
PIONEER 3: Explore the head-to-head study results for RYBELSUS® vs the most prescribed DPP-4i3
26-WEEK RESULTS
Superior A1C reduction vs Januvia®1
63% greater A1C reduction with RYBELSUS® 14 mg vs Januvia®
See study design below.
52-WEEK RESULTS
Statistically significant A1C reduction vs Januvia®2,4*
A1C reduction demonstrated at 52 weeks
ETD=estimated treatment difference.
*Endpoint not adjusted for multiplicity.
26-WEEK RESULTS
Superior A1C control vs Januvia®1,3*
1.7x more patients achieved an A1C target <7% with RYBELSUS® 14 mg vs Januvia®
See study design below.
52-WEEK RESULTS
Statistically significant A1C control vs Januvia®2,4*
Sustainable A1C control demonstrated at 52 weeks
*Endpoint not adjusted for multiplicity.
26-WEEK RESULTS
Superior weight reduction with RYBELSUS® 14 mg and 7 mg vs Januvia®1,2
RYBELSUS® is not indicated for weight loss.
Mean change in body weight from baseline to Week 26 was a confirmatory secondary endpoint.
See study design below.
52-WEEK RESULTS
Statistically significant weight reduction with RYBELSUS® 14 mg and 7 mg vs Januvia®2,4*
RYBELSUS® is not indicated for weight loss.
Mean change in body weight from baseline to Week 52 was a secondary endpoint.
ETD=estimated treatment difference.
*Endpoint not adjusted for multiplicity.
PIONEER 3 Study Design: RYBELSUS® vs Januvia®1,2
Objective
Compare treatment of RYBELSUS® to Januvia® for A1C reductions in adult patients with type 2 diabetes.
- double-blind
- double-dummy
Patients
1864 adult patients with type 2 diabetes on metformin alone or metformin with a sulfonylurea
Treatment arms
Patients were randomized to RYBELSUS® 3 mg (n=466), RYBELSUS® 7 mg (n=465), RYBELSUS® 14 mg (n=465), or Januvia® 100 mg (n=467), all once daily.
Primary endpoint
Mean change in A1C from baseline to 26 weeks1,2
Confirmatory secondary endpoint
Mean change in body weight from baseline to Week 261,2
Select secondary endpoints
Proportion of patients achieving A1C <7% at Week 26 and 52, and mean changes from baseline to Week 52 in A1C and body weight1,2
A1C=glycated hemoglobin; DPP-4i=dipeptidyl peptidase-4 inhibitor.
RYBELSUS® has wider commercial coverage than Januvia®a,b
aCalculated with noninsulin antidiabetic drugs (NIAD) market volume (previously GLP-1) to prepare for RYBELSUS® access calculations. Sources: Data from MMIT Formulary bridge. June 2024 Nomenclature and Xponent PlanTrak using week-ending 6/21/2024; only considers bridged volume; excludes cash and mail order data; based on full DCS/EDCS/CARD/OCS IC universe (Targets + Non-Targets). Unrestricted defined as Preferred + Covered.
bNovo Nordisk defines formulary coverage as Preferred, Covered, or Covered with Restrictions. Coverage status and tier vary by plan and are subject to change. Please check directly with the health plan to confirm coverage for individual patients.
Important Safety Information for RYBELSUS®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- RYBELSUS® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of RYBELSUS® and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with RYBELSUS®
Contraindications
- RYBELSUS® is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), and in patients with a prior serious hypersensitivity reaction to semaglutide or to any of the excipients in RYBELSUS®. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with RYBELSUS®
Warnings and Precautions
- Risk of Thyroid C-Cell Tumors: Patients should be further evaluated if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including RYBELSUS®. Observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue RYBELSUS® and initiate appropriate management
- Diabetic Retinopathy Complications: In a pooled analysis of glycemic control trials with RYBELSUS®, patients reported diabetic retinopathy related adverse reactions during the trial (4.2% with RYBELSUS® and 3.8% with comparator). In a 2-year trial with semaglutide injection involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with semaglutide injection (3.0%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline than among patients without a known history of diabetic retinopathy.
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy - Hypoglycemia: Patients receiving RYBELSUS® in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia
- Acute Kidney Injury: There have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis, in patients treated with GLP-1 receptor agonists, including semaglutide. Some of these events have been reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Monitor renal function when initiating or escalating doses of RYBELSUS® in patients reporting severe adverse gastrointestinal reactions
- Severe Gastrointestinal Adverse Reactions: Use of RYBELSUS® has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving RYBELSUS® (7 mg 0.6%, 14 mg 2%) than placebo (0.3%). RYBELSUS® is not recommended in patients with severe gastroparesis
- Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with RYBELSUS®. If hypersensitivity reactions occur, discontinue use of RYBELSUS®, treat promptly per standard of care, and monitor until signs and symptoms resolve. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials, cholelithiasis was reported in 1% of patients treated with RYBELSUS® 7 mg. Cholelithiasis was not reported in RYBELSUS® 14 mg or placebo-treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: RYBELSUS® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking RYBELSUS®
Adverse Reactions
- Most common adverse reactions (incidence ≥5%) are nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation
Drug Interactions
- RYBELSUS® stimulates insulin release in the presence of elevated blood glucose concentrations. When initiating RYBELSUS®, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
- RYBELSUS® delays gastric emptying and has the potential to impact the absorption of other oral medications. Closely follow RYBELSUS® administration instructions when coadministering with other oral medications and consider increased monitoring for medications with a narrow therapeutic index, such as levothyroxine
Use in Specific Populations
- Pregnancy: Available data with RYBELSUS® are not sufficient to determine a drug associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Discontinue RYBELSUS® in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide
- Lactation: A clinical lactation study reported semaglutide concentrations below the lower limit of quantification in human breast milk. However, salcaprozate sodium (SNAC) and/or its metabolites are present in human milk. Because of the unknown potential for serious adverse reactions in the breastfed infant due to the possible accumulation of SNAC, an absorption enhancer for RYBELSUS®, and because there are alternative formulations of semaglutide that do not contain SNAC that can be used during lactation, advise patients that breastfeeding is not recommended during treatment with RYBELSUS®
- Pediatric Use: Safety and effectiveness of RYBELSUS® have not been established in pediatric patients
Please click here for RYBELSUS® Prescribing Information, including Boxed Warning.
Important Safety Information for RYBELSUS®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- RYBELSUS® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of RYBELSUS® and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with RYBELSUS®
Important Safety Information for RYBELSUS®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- RYBELSUS® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of RYBELSUS® and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with RYBELSUS®
Contraindications
- RYBELSUS® is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), and in patients with a prior serious hypersensitivity reaction to semaglutide or to any of the excipients in RYBELSUS®. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with RYBELSUS®
Warnings and Precautions
- Risk of Thyroid C-Cell Tumors: Patients should be further evaluated if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including RYBELSUS®. Observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue RYBELSUS® and initiate appropriate management
- Diabetic Retinopathy Complications: In a pooled analysis of glycemic control trials with RYBELSUS®, patients reported diabetic retinopathy related adverse reactions during the trial (4.2% with RYBELSUS® and 3.8% with comparator). In a 2-year trial with semaglutide injection involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with semaglutide injection (3.0%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline than among patients without a known history of diabetic retinopathy.
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy - Hypoglycemia: Patients receiving RYBELSUS® in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia
- Acute Kidney Injury: There have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis, in patients treated with GLP-1 receptor agonists, including semaglutide. Some of these events have been reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Monitor renal function when initiating or escalating doses of RYBELSUS® in patients reporting severe adverse gastrointestinal reactions
- Severe Gastrointestinal Adverse Reactions: Use of RYBELSUS® has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving RYBELSUS® (7 mg 0.6%, 14 mg 2%) than placebo (0.3%). RYBELSUS® is not recommended in patients with severe gastroparesis
- Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with RYBELSUS®. If hypersensitivity reactions occur, discontinue use of RYBELSUS®, treat promptly per standard of care, and monitor until signs and symptoms resolve. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials, cholelithiasis was reported in 1% of patients treated with RYBELSUS® 7 mg. Cholelithiasis was not reported in RYBELSUS® 14 mg or placebo-treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: RYBELSUS® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking RYBELSUS®
Adverse Reactions
- Most common adverse reactions (incidence ≥5%) are nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation
Drug Interactions
- RYBELSUS® stimulates insulin release in the presence of elevated blood glucose concentrations. When initiating RYBELSUS®, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
- RYBELSUS® delays gastric emptying and has the potential to impact the absorption of other oral medications. Closely follow RYBELSUS® administration instructions when coadministering with other oral medications and consider increased monitoring for medications with a narrow therapeutic index, such as levothyroxine
Use in Specific Populations
- Pregnancy: Available data with RYBELSUS® are not sufficient to determine a drug associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Discontinue RYBELSUS® in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide
- Lactation: A clinical lactation study reported semaglutide concentrations below the lower limit of quantification in human breast milk. However, salcaprozate sodium (SNAC) and/or its metabolites are present in human milk. Because of the unknown potential for serious adverse reactions in the breastfed infant due to the possible accumulation of SNAC, an absorption enhancer for RYBELSUS®, and because there are alternative formulations of semaglutide that do not contain SNAC that can be used during lactation, advise patients that breastfeeding is not recommended during treatment with RYBELSUS®
- Pediatric Use: Safety and effectiveness of RYBELSUS® have not been established in pediatric patients
Please click here for RYBELSUS® Prescribing Information, including Boxed Warning.
References:
- RYBELSUS® [package insert]. Plainsboro, NJ: Novo Nordisk Inc.
- Rosenstock J, Allison D, Birkenfeld AL, et al. Effect of additional oral semaglutide vs sitagliptin on glycated hemoglobin in adults with type 2 diabetes uncontrolled with metformin alone or with sulfonylurea: the PIONEER 3 randomized clinical trial. JAMA. 2019;321(15):1466-1480.
- IQVIA weekly NPA (TRx count), latest 26 weeks ending 9/18/2023.
- Data on file. Novo Nordisk Inc; November 2018.