Rybelsus ®(Oral Semaglutide)

Xultophy®(Insulin Degludec And Liraglutide)

Prescription Only

Rybelsus tablets (semaglutide) are used by adults with type 2 diabetes to manage blood sugar levels. Taken once daily, Rybelsus is combined with diet and exercise. It boosts...

Prescription Only

Xultophy is an injection pen combining insulin degludec and liraglutide. Insulin degludec provides long-acting glucose control, while liraglutide assists in regulating blood...

Dosage & Administration

Administration

Oral. Learn more.

Subcutaneous. Learn more.

Dosing

Start RYBELSUS® with 3 mg once daily for 30 days. The 3 mg dosage is intended for treatment initiation. •After 30 days on the 3 mg dosage, increase the dosage to 7 mg once daily. •The dosage may be increased to 14 mg.. Learn more.

Administer XULTOPHY® 100/3.6 by subcutaneous injection once-daily at the same time each day with or without food. See complete table for starting dose and titration schedule in the PI.. Learn more.

Latin Shorthand

Initiate RYBELSUS® at 3 mg qd for 30 days. Then, escalate to 7 mg qd after 30 days. Consider up-titrating to 14 mg qd.. Learn more.

Administer XULTOPHY® 100/3.6 by SC injection qd at the same time each day with or without food.. Learn more.

Financial Assistance

Out-Of-Pocket Costs With Copay Card

$25. Learn more.

Insurance Specific Copay. Learn more.

Annual Cap

$150 for a 1-month supply; $300 for a 2-month supply; $450 for a 3-month supply. Learn more.

Learn more.

Assistance Expiration

24 months. Learn more.

Learn more.

Generics

No lower-cost generic available

Physician Advisory

Adverse Reactions

Most common adverse reactions (incidence ≥5%) are nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation.. Learn more.

• Most common adverse reactions (incidence ≥5%) in clinical trials are nasopharyngitis, headache, nausea, diarrhea, increased lipase and upper respiratory tract infection. • Immunogenicity-related events, including urticaria, were more common among liraglutide-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials.. Learn more.

Mechanism of Actions (MoA)

GLP-1 Receptor Agonists. Learn more.

Special Populations

What is the risk of using RYBELSUS® during pregnancy?

The available data with RYBELSUS® use in pregnant women are insufficient to evaluate the drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Clinical considerations should be noted regarding the risks of poorly controlled diabetes during pregnancy.

How should RYBELSUS® be used during pregnancy?

RYBELSUS® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

What animal reproduction studies have been conducted with RYBELSUS®?

In pregnant rats, embryofetal mortality, structural abnormalities, and alterations to growth occurred at maternal exposures below the maximum recommended human dose (MRHD) based on AUC. Similar findings were observed in rabbits and cynomolgus monkeys at exposures below the MRHD.

What is the estimated background risk of major birth defects and miscarriage?

The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with an HbA1c >7, and has been reported to be as high as 20–25% in women with a HbA1c >10. In the general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

What are the clinical considerations for poorly controlled diabetes during pregnancy?

Poorly controlled diabetes during pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. It also increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.

Is there any information on RYBELSUS® use during lactation?

There are no data on the presence of semaglutide (active ingredient in RYBELSUS®) in human milk, its effects on the breastfed infant, or milk production. Semaglutide was detected in the milk of lactating rats. Due to species-specific differences, the clinical relevance of these data is not clear.

What should be considered regarding lactation and RYBELSUS®?

Breastfeeding is not recommended during treatment with RYBELSUS® due to potential accumulation of certain substances (such as SNAC) in breast milk. There are alternative formulations of semaglutide that can be used during lactation.

When should RYBELSUS® be discontinued in relation to a planned pregnancy?

RYBELSUS® should be discontinued in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide.

Is RYBELSUS® safe for pediatric use?

The safety and effectiveness of RYBELSUS® have not been established in pediatric patients (younger than 18 years).

How is RYBELSUS® affected by renal impairment?

The safety and effectiveness of RYBELSUS® was evaluated in patients with moderate renal impairment, showing no clinically relevant change in semaglutide pharmacokinetics. No dose adjustment of RYBELSUS® is recommended for patients with renal impairment.

How is RYBELSUS® affected by hepatic impairment?

In subjects with different degrees of hepatic impairment, no clinically relevant change in semaglutide pharmacokinetics was observed. No dose adjustment of RYBELSUS® is recommended for patients with hepatic impairment.

Is there a risk to the fetus from exposure to liraglutide during pregnancy?

Based on animal reproduction studies, there may be risks to the fetus from exposure to liraglutide during pregnancy. XULTOPHY® 100/3.6 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Are there available data on the use of XULTOPHY® 100/3.6, insulin degludec, or liraglutide in pregnant women?

There are no available data with XULTOPHY® 100/3.6, insulin degludec, or liraglutide in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. There are clinical considerations regarding the risks of poorly controlled diabetes in pregnancy.

What are the findings from animal reproduction studies for insulin degludec during pregnancy?

For insulin degludec, rats and rabbits were exposed in animal reproduction studies at 5 times (rat) and 10 times (rabbit) the human exposure at a dose of 0.75 U/kg/day. No adverse outcomes were observed for pregnant animals and offspring.

What are the findings from animal reproduction studies for liraglutide during pregnancy?

For liraglutide, animal reproduction studies identified increased adverse developmental outcomes from exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 1.8 mg/day.

What is the estimated background risk of major birth defects and miscarriage in the general population and in women with pre-gestational diabetes?

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a peri-conceptional HbA1c >7 and has been reported to be as high as 20 to 25% in women with a peri-conceptional HbA1c >10.

What are the disease-associated maternal and/or embryo/fetal risks related to poorly controlled diabetes in pregnancy?

Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.

Are there data on the presence of liraglutide or insulin degludec in human milk, their effects on the breastfed infant, or effects on milk production?

There are no data on the presence of liraglutide or insulin degludec in human milk, the effects on the breastfed infant, or the effects on milk production. In lactating rats, insulin degludec and liraglutide, the two components of XULTOPHY® 100/3.6, were present in milk.

What are the safety and effectiveness considerations for pediatric use of XULTOPHY® 100/3.6?

Safety and effectiveness of XULTOPHY® 100/3.6 have not been established in pediatric patients.

Are there age-related differences in safety and effectiveness for geriatric patients using XULTOPHY® 100/3.6?

No overall differences in safety or effectiveness of XULTOPHY® 100/3.6 were observed between patients 65 years of age and older and younger patients. Age had no clinically relevant effect on the pharmacokinetics of XULTOPHY® 100/3.6.

What are the considerations for XULTOPHY® 100/3.6 use in patients with renal impairment?

There is limited experience with XULTOPHY® 100/3.6 in patients with mild and moderate kidney impairment and when used in these patients, additional glucose monitoring and XULTOPHY® 100/3.6 dose adjustments may be required on an individual basis. XULTOPHY® 100/3.6 has not been studied in patients with severe kidney impairment.

Are there any differences in insulin degludec pharmacokinetics in patients with kidney impairment?

No clinically relevant difference in the pharmacokinetics of insulin degludec was identified in a study comparing healthy subjects and subjects with kidney impairment, including subjects with end stage kidney disease.

What is the effect of liraglutide on kidney impairment?

The safety and efficacy of liraglutide was evaluated in a 26-week clinical study that included patients with moderate kidney impairment. There is limited experience with liraglutide in patients with end stage kidney disease.

Are there considerations for XULTOPHY® 100/3.6 use in patients with hepatic impairment?

XULTOPHY® 100/3.6 has not been studied in patients with hepatic impairment.

Are there any differences in insulin degludec pharmacokinetics in patients with hepatic impairment?

No clinically relevant difference in the pharmacokinetics of insulin degludec, one of the components of XULTOPHY® 100/3.6, was identified in a study comparing healthy subjects and subjects with hepatic impairment.

What is the effect of liraglutide on hepatic impairment?

There is limited experience in patients with mild, moderate, or severe hepatic impairment with liraglutide, one of the components of XULTOPHY® 100/3.6.

Does liraglutide, a component of XULTOPHY® 100/3.6, have an impact on gastric emptying?

Liraglutide, one of the components of XULTOPHY® 100/3.6, slows gastric emptying. XULTOPHY® 100/3.6 has not been studied in patients with pre-existing gastroparesis.

Rybelsus ®(Oral Semaglutide)	Xultophy®(Insulin Degludec And Liraglutide)

Prescription Only Rybelsus tablets (semaglutide) are used by adults with type 2 diabetes to manage blood sugar levels. Taken once daily, Rybelsus is combined with diet and exercise. It boosts...	Prescription Only Xultophy is an injection pen combining insulin degludec and liraglutide. Insulin degludec provides long-acting glucose control, while liraglutide assists in regulating blood...
Dosage & Administration	Dosage & Administration comparison data
Administration
Oral. Learn more.	Subcutaneous. Learn more.
Dosing
Start RYBELSUS® with 3 mg once daily for 30 days. The 3 mg dosage is intended for treatment initiation. •After 30 days on the 3 mg dosage, increase the dosage to 7 mg once daily. •The dosage may be increased to 14 mg.. Learn more.	Administer XULTOPHY® 100/3.6 by subcutaneous injection once-daily at the same time each day with or without food. See complete table for starting dose and titration schedule in the PI.. Learn more.
Latin Shorthand
Initiate RYBELSUS® at 3 mg qd for 30 days. Then, escalate to 7 mg qd after 30 days. Consider up-titrating to 14 mg qd.. Learn more.	Administer XULTOPHY® 100/3.6 by SC injection qd at the same time each day with or without food.. Learn more.
Financial Assistance	Financial Assistance comparison data
Out-Of-Pocket Costs With Copay Card
$25. Learn more.	Insurance Specific Copay. Learn more.
Annual Cap
$150 for a 1-month supply; $300 for a 2-month supply; $450 for a 3-month supply. Learn more.	Learn more.
Assistance Expiration
24 months. Learn more.	Learn more.
Generics
No lower-cost generic available	No lower-cost generic available
Physician Advisory	Physician Advisory comparison data
Adverse Reactions
Most common adverse reactions (incidence ≥5%) are nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation.. Learn more.	• Most common adverse reactions (incidence ≥5%) in clinical trials are nasopharyngitis, headache, nausea, diarrhea, increased lipase and upper respiratory tract infection. • Immunogenicity-related events, including urticaria, were more common among liraglutide-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials.. Learn more.
Mechanism of Actions (MoA)
GLP-1 Receptor Agonists. Learn more.	GLP-1 Receptor Agonists. Learn more.
Special Populations
What is the risk of using RYBELSUS® during pregnancy? The available data with RYBELSUS® use in pregnant women are insufficient to evaluate the drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Clinical considerations should be noted regarding the risks of poorly controlled diabetes during pregnancy. How should RYBELSUS® be used during pregnancy? RYBELSUS® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. What animal reproduction studies have been conducted with RYBELSUS®? In pregnant rats, embryofetal mortality, structural abnormalities, and alterations to growth occurred at maternal exposures below the maximum recommended human dose (MRHD) based on AUC. Similar findings were observed in rabbits and cynomolgus monkeys at exposures below the MRHD. What is the estimated background risk of major birth defects and miscarriage? The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with an HbA1c >7, and has been reported to be as high as 20–25% in women with a HbA1c >10. In the general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. What are the clinical considerations for poorly controlled diabetes during pregnancy? Poorly controlled diabetes during pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. It also increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Is there any information on RYBELSUS® use during lactation? There are no data on the presence of semaglutide (active ingredient in RYBELSUS®) in human milk, its effects on the breastfed infant, or milk production. Semaglutide was detected in the milk of lactating rats. Due to species-specific differences, the clinical relevance of these data is not clear. What should be considered regarding lactation and RYBELSUS®? Breastfeeding is not recommended during treatment with RYBELSUS® due to potential accumulation of certain substances (such as SNAC) in breast milk. There are alternative formulations of semaglutide that can be used during lactation. When should RYBELSUS® be discontinued in relation to a planned pregnancy? RYBELSUS® should be discontinued in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide. Is RYBELSUS® safe for pediatric use? The safety and effectiveness of RYBELSUS® have not been established in pediatric patients (younger than 18 years). How is RYBELSUS® affected by renal impairment? The safety and effectiveness of RYBELSUS® was evaluated in patients with moderate renal impairment, showing no clinically relevant change in semaglutide pharmacokinetics. No dose adjustment of RYBELSUS® is recommended for patients with renal impairment. How is RYBELSUS® affected by hepatic impairment? In subjects with different degrees of hepatic impairment, no clinically relevant change in semaglutide pharmacokinetics was observed. No dose adjustment of RYBELSUS® is recommended for patients with hepatic impairment.	Is there a risk to the fetus from exposure to liraglutide during pregnancy? Based on animal reproduction studies, there may be risks to the fetus from exposure to liraglutide during pregnancy. XULTOPHY® 100/3.6 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Are there available data on the use of XULTOPHY® 100/3.6, insulin degludec, or liraglutide in pregnant women? There are no available data with XULTOPHY® 100/3.6, insulin degludec, or liraglutide in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. There are clinical considerations regarding the risks of poorly controlled diabetes in pregnancy. What are the findings from animal reproduction studies for insulin degludec during pregnancy? For insulin degludec, rats and rabbits were exposed in animal reproduction studies at 5 times (rat) and 10 times (rabbit) the human exposure at a dose of 0.75 U/kg/day. No adverse outcomes were observed for pregnant animals and offspring. What are the findings from animal reproduction studies for liraglutide during pregnancy? For liraglutide, animal reproduction studies identified increased adverse developmental outcomes from exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 1.8 mg/day. What is the estimated background risk of major birth defects and miscarriage in the general population and in women with pre-gestational diabetes? In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a peri-conceptional HbA1c >7 and has been reported to be as high as 20 to 25% in women with a peri-conceptional HbA1c >10. What are the disease-associated maternal and/or embryo/fetal risks related to poorly controlled diabetes in pregnancy? Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Are there data on the presence of liraglutide or insulin degludec in human milk, their effects on the breastfed infant, or effects on milk production? There are no data on the presence of liraglutide or insulin degludec in human milk, the effects on the breastfed infant, or the effects on milk production. In lactating rats, insulin degludec and liraglutide, the two components of XULTOPHY® 100/3.6, were present in milk. What are the safety and effectiveness considerations for pediatric use of XULTOPHY® 100/3.6? Safety and effectiveness of XULTOPHY® 100/3.6 have not been established in pediatric patients. Are there age-related differences in safety and effectiveness for geriatric patients using XULTOPHY® 100/3.6? No overall differences in safety or effectiveness of XULTOPHY® 100/3.6 were observed between patients 65 years of age and older and younger patients. Age had no clinically relevant effect on the pharmacokinetics of XULTOPHY® 100/3.6. What are the considerations for XULTOPHY® 100/3.6 use in patients with renal impairment? There is limited experience with XULTOPHY® 100/3.6 in patients with mild and moderate kidney impairment and when used in these patients, additional glucose monitoring and XULTOPHY® 100/3.6 dose adjustments may be required on an individual basis. XULTOPHY® 100/3.6 has not been studied in patients with severe kidney impairment. Are there any differences in insulin degludec pharmacokinetics in patients with kidney impairment? No clinically relevant difference in the pharmacokinetics of insulin degludec was identified in a study comparing healthy subjects and subjects with kidney impairment, including subjects with end stage kidney disease. What is the effect of liraglutide on kidney impairment? The safety and efficacy of liraglutide was evaluated in a 26-week clinical study that included patients with moderate kidney impairment. There is limited experience with liraglutide in patients with end stage kidney disease. Are there considerations for XULTOPHY® 100/3.6 use in patients with hepatic impairment? XULTOPHY® 100/3.6 has not been studied in patients with hepatic impairment. Are there any differences in insulin degludec pharmacokinetics in patients with hepatic impairment? No clinically relevant difference in the pharmacokinetics of insulin degludec, one of the components of XULTOPHY® 100/3.6, was identified in a study comparing healthy subjects and subjects with hepatic impairment. What is the effect of liraglutide on hepatic impairment? There is limited experience in patients with mild, moderate, or severe hepatic impairment with liraglutide, one of the components of XULTOPHY® 100/3.6. Does liraglutide, a component of XULTOPHY® 100/3.6, have an impact on gastric emptying? Liraglutide, one of the components of XULTOPHY® 100/3.6, slows gastric emptying. XULTOPHY® 100/3.6 has not been studied in patients with pre-existing gastroparesis.

Rybelsus ® Alternatives