Rybelsus® - Semaglutide as the world's first and only oral GLP-1 analogue

People with type 2 diabetes have too little endogenous GLP-1 (glucagon-like peptide 1) or its effect is reduced. Semaglutide, mimicking natural GLP-1, can compensate for this^.1 It lowers blood glucose, supports weight loss and cardiovascular burden reduction^.1,2,* ^Rybelsus® (semaglutide) is now approved in Switzerland as the world’s first and only oral GLP-1 analog for patients with inadequately controlled T2DM^.1

When we eat, our intestines produce a substance called GLP-1. This stimulates the secretion of insulin in the pancreas in a glucose-dependent manner and inhibits that of glucagon. In addition, GLP-1 slows gastric emptying, increases the feeling of satiety and centrally regulates cravings. This prevents the blood sugar from rising too high. In patients with type 2 diabetes, too little GLP-1 is probably released or its effect is impaired, which increases the blood glucose level and subsequently also the long-term blood glucose value HbA1C. The latter is a risk factor for various secondary diseases.

Semaglutide – a modern and potent GLP-1 analogue

Semaglutide is a modern and potent GLP-1 analogue that mimics natural GLP-1.^1,2 The optimized active ingredient is degraded in a delayed manner, which prolongs its duration of action and opens up new application possibilities.⁴ Semaglutide can do the following:

It lowers elevated blood glucose in a glucose-dependent manner, thereby significantly lowering patients’ HbA1C.^1,2
By regulating the feeling of satiety and hunger, it can lead to weight loss.^1,2,*

All of this helps patients with inadequately controlled type 2 diabetes and obesity (BMI ≥ 28) achieve their treatment goals and prevent microvascular and macrovascular sequelae thanks to Semaglutide.^1,2,* For these patients, a reduction in their cardiovascular burden is of key importance (prevention of myocardial infarction, stroke, etc.).³ The PIONEER 6 clinical trial of the cardiovascular outcome of oral semaglutide was able to demonstrate a numerically reduced cardiovascular risk (vs. placebo).^1,5,*

Semaglutide (^Rybelsus®) as the world’s first and only oral GLP-1 analogue

In diabetes therapy, a departure for new shores is now beginning. Since April 2020, ^Rybelsus® has been approved by Swissmedic in Switzerland for patients with T2DM, as the world’s first and only oral GLP-1 analog. The good efficacy of Semaglutide opens up about the simple intake of Rybelsus^® an even larger group of patients: now it is possible to choose between a once-daily Rybelsus^® tablet and the once-weekly subcutaneous Ozempic^® be chosen.1,2 With Rybelsus^® 7 out of 10 patients achieve a treatment target of HbA1C ≤7%, with sustained effect.¹ This and the consistent weight loss with ^Rybelsus® is significantly better compared to other modern antidiabetic agents.^1,2,*,** The individually tunable patient benefit enables the optimization of compliance and thus effective prevention of secondary diseases.⁶

* ^Rybelsus® and ^Ozempic® are indicated for the treatment of inadequately controlled type 2 diabetes mellitus in addition to diet and exercise, but are not indicated for weight loss or reduction of cardiovascular events. ** Clinical trials showed significantly better glycemic control (baseline HbA1C during study duration) and weight reduction (change in body weight during study duration) for semaglutide vs. placebo (PIONEER 8^)1,7, vs. empagliflozin (PIONEER 2^)1,8, vs. sitagliptin (PIONEER 3 and PIONEER 7^)1,9,10, and vs. liraglutide (PIONEER 4)1^,11.

Abbreviations: CVOT: cardiovascular outcome study; GLP-1: glucagon-like peptide 1; T2DM: type 2 diabetes.

References

^Rybelsus® Specialty Information, www.swissmedicinfo.ch.
^Ozempic® SmPC, www.swissmedicinfo.ch.
SGED/SSED Working Group. Recommendations of the Swiss Society of Endocrinology and Diabetology (SGED/SSED) for the treatment of type 2 diabetes mellitus (2020). Status: January 23, 2020. Available at: https://www.sgedssed.ch/fileadmin/user_upload/6_Diabetologie/61_Empfehlungen_Facharzt/-2020_Swiss_Recomm_Medis_DE_def.pdf, last accessed 05/2020.
Lau et al. Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide. J Med Chem. 2015; 58:7370-80.
Husain et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2019;381(9):841-51.
Polonsky et al. Patient perspectives on once-weekly medications for diabetes. Diabetes Obes Metab. 2011;13(2):144-9.
Zinman et al. Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. Diabetes Care. 2019;42(12):2262-71.
Rodbard et al. Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial. Diabetes Care. 2019;42(12):2272-81.
Rosenstock 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):1466-80.
Pieber et al. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019;7(7):528-39.
Pratley et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet. 2019;394(10192):39-50.

Limitatio ^Rybelsus®: For the treatment of patients with type 2 diabetes mellitus; in exclusively following combination therapies when adequate glycemic control is not achieved by these antidiabetic agents.

As a two-drug combination with metformin or a sulfonylurea
As a triple combination with a combination of metformin and a sulfonylurea
In combination with basal insulin with or without metformin.

Minimum BMI 28. Additional weight loss medications are not covered by health insurance.

Rybelsus® ^Z: Semaglutide 3 mg, 7 mg, 14 mg per tablet. I: ^Rybelsus® is used for the treatment of adults with inadequately controlled type 2 diabetes mellitus in addition to diet and exercise: – as monotherapy in case of contraindication or intolerance to metformin; – in combination with other blood glucose-lowering drugs. See Clinical Efficacy section for results on combinations studied in clinical trials and cardiovascular safety. D: Starting dose of ^Rybelsus® is 3 mg once daily. After 1 month, increase dose to 7 mg once daily (maintenance dose). If blood glucose-lowering effect is insufficient after one month of treatment Increase maintenance dose to 14 mg once daily. Dose adjustment not required in the elderly and patients with impaired hepatic or renal function. ^Rybelsus® is a tablet for once-daily oral use. Swallow ^Rybelsus® whole on an empty stomach with up to half a glass of water (120 ml). Wait at least 30 minutes before taking first meal, first drink, or other oral medication. KI: Hypersensitivity to the active substance or to one of the excipients according to “Composition”. VM: Do not use ^Rybelsus® in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Use of GLP-1 receptor agonists may be associated with adverse gastrointestinal effects. Discontinue ^Rybelsus® if pancreatitis is suspected. Increased risk of hypoglycemia when combined with sulfonylurea or insulin. Monitor patients with a history of diabetic retinopathy. IA: Semaglutide delays gastric emptying. This may affect the absorption of other drugs used at the same time. UW: Very common: hypoglycemia when used with insulin or SU, nausea, diarrhea; common: hypoglycemia when used with other OAD, decreased appetite, complications of diabetic retinopathy, vomiting, abdominal pain, abdominal tightness, constipation, dyspepsia, gastritis, gastroesophageal reflux, flatulence, increased lipase, increased amylase, fatigue. Occasional: increased heart rate, belching, cholelithiasis, weight loss. Rare: anaphylactic reactions. P: 3 mg: Packs of 30 tablets. 7 mg: packs of 30 and 90 tablets, 14 mg: packs of 30 and 90 tablets (B). Version 1.0. For detailed information, please visit www.swissmedicinfo.ch.

▼Thismedicinal product is subject to additional monitoring. For further information, see ^Rybelsus® technical information at www.swissmedicinfo.ch.

Limitatio ^Ozempic®: For the treatment of patients with type 2 diabetes, in exclusive combination therapy with metformin, a sulfonylurea, or a combination of metformin and a sulfonylurea, when adequate glycemic control is not achieved with these oral antidiabetic agents. For treatment as combination therapy with a basal insulin alone or a combination of a basal insulin with metformin when adequate glycemic control is not achieved with these treatments. Minimum BMI 28. Additional weight loss medications are not covered by health insurance.

^Ozempic® Z: Semaglutide 1.34 mg/ml. I: ^Ozempic® is used to treat adults with inadequately controlled type 2 diabetes mellitus as an adjunct to diet and exercise: as monotherapy when contraindicated or intolerant to metformin; in combination with other antihyperglycemic drugs. D: The starting dose of ^Ozempic® is 0.25 mg once weekly. After 4 weeks, the dose should be increased to 0.5 mg once weekly. To improve blood glucose control, after at least 4 more weeks at a dose of 0.5 mg once per week, the dose may be increased to 1 mg once per week. Dose adjustment is not required in the elderly, in patients with impaired renal or hepatic function. ^Ozempic® is used once a week at any time and independently of meals. AI: Hypersensitivity to the active substance or to one of the excipients according to “Composition”. VM: ^Ozempic® should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. The use of GLP-1 receptor agonists may be associated with adverse gastrointestinal effects. If pancreatitis is suspected, ^Ozempic® should be discontinued. Patients receiving ^Ozempic® in combination with a sulfonylurea or insulin may be at increased risk for hypoglycemia. ^Ozempic® should be used in patients with diabetic retinopathy only under close ophthalmologic control. IA: Gastric emptying delayed by Semaglutide may affect the absorption of concomitant oral medications. UW: Very common: hypoglycemia when used with insulin or sulfonylurea, nausea, diarrhea. Common: hypoglycemia when used with other OAD’s, decreased appetite, dizziness, complications of diabetic retinopathy, vomiting, abdominal pain, abdominal tightness, constipation, dyspepsia, gastritis, gastroesophageal reflux, belching, flatulence, cholelithiasis, increased lipase, increased amylase, weight loss, fatigue. Occasional: dysgeusia, increased heart rate, injection site reactions, acute pancreatitis. Rare: Anaphylactic reaction. P: ^Ozempic® DualDose 0.25 mg or 0.5 mg: 1 prefilled pen of 1.5 ml; ^Ozempic® FixDose 1 mg: 2 prefilled pens of 1.5 ml, 1 prefilled pen of 3 ml (B). V4.0. For detailed information, please visit www.swissmedicinfo.ch.