Rybelsus for Weight Loss



Rybelsus (GLP-1 oral medicine)

Rybelsus is an oral medication that contains Semaglutide, a GLP-1 receptor agonist.

GLP-1 receptor agonists act on the GLP-1 receptors in brain cells to increase satiety, decrease hunger, suppress appetite, and reduce body weight.

Although it is approved as a diabetes medication, prescribing Rybelsus for weight loss purposes is considered an off-label use and is not covered under the relief system for pharmaceutical side effects as it is an unapproved drug for obesity treatment.

Prescribing Rybelsus requires a medical examination, informed consent regarding potential side effects, and regular monitoring of side effects by a physician.

Weight Loss Effect

The percentage of weight loss of 5% or more
Rybelsus 3mg
Rybelsus 7mg

In a study conducted at 93 facilities across nine countries for type 2 diabetes, the proportion of subjects who experienced a weight loss of 5% or more after 26 weeks (approximately 6 months) was reported to be 21.3% for the 3mg dose of Rybelsus, 28.7% for the 7mg dose, and 44.3% for the 14mg dose, compared to 15.7% for the placebo group (Figure7).

In other studies, the proportion of subjects who experienced a weight loss of 5% or more after 26 weeks was reported to be 11% for the 7mg dose of Rybelsus, 36% for the 14mg dose, and 7% for the placebo group, and after 52 weeks (approximately one year), the proportions were 12% for the 7mg dose, 41% for the 14mg dose, and 6% for the placebo group.

The average weight loss rate for the Rybelsus 14mg group at six months was reported to be -2.2% to -4.2%9-13.

Weight change after discontinuation

After discontinuing GLP-1 therapy, appetite gradually returns to normal and weight is more likely to be regained without any action. It is important to combine dietary and exercise therapy to establish habits that make weight loss easier.

Dosage and Administration of Rybelsus

Rybelsus3mg / 7mg / 14mg

How to take Rybelsus

Take one tablet with about half a glass of water (less than 120mL) on an empty stomach before the first meal or drink of the day. After taking the tablet, do not eat, drink, or take any other medication for at least 30 minutes. Do not split, chew, or take two tablets at once.


Start with 3mg once a day and increase to 7mg once a day after one month.

If the effect is insufficient even after taking 7mg for more than one month, increase to 14mg once a day.

Treatment Period

We recommend a treatment period of 6 to 12 months. The dosage and duration will be determined based on the progress of the treatment.

Those who cannot take Rybelsus

  1. Patients under 18 years of age or over 75 years of age.
  2. Patients with diabetes, pancreatitis, cholelithiasis, cholecystitis, severe renal or hepatic dysfunction.
  3. Patients with a history of abdominal surgery or bowel obstruction.
  4. Patients with eating disorders, BMI less than 18.5, body fat percentage less than 15% for men and 25% for women.
  5. Patients with obesity caused by endocrine disorders or drugs such as steroids.
  6. Patients with thyroid disease or a family history of multiple endocrine neoplasia type 2.
  7. Those who are planning to be pregnant, who are pregnant or under breast feeding.
  8. Patients with depression or suicide attempts.
  9. Those who are allergic to Semaglutide (Rybelsus, Ozempic), additives (Salcaprozate sodium, povidone, crystalline cellulose, magnesium stearate)

Side effects of Rybelsus

The following are side effects in patients with type 2 diabetes; no studies have been conducted for side effects in patients other than type 2 diabetes.

side effect>5%1~5%0.5~1%Frequency unknown
Metabolism, Nutritiondecrease in appetite
Nerve systemheadachedizziness, impaired taste
Eyediabetic retinopathy
Gastrointestinalnausea, diarrheaconstipation, vomiting, abdominal discomfort, abdominal pain, abdominal distension, GERDbloating, gastritis, belching
Liver, bile ductsGall stone
Generalpowerless, malaise
Blood testElevated level of lipaseElevated level of amylase or CK
  • Gastrointestinal symptoms: Nausea, vomiting, diarrhea, and constipation are the most common side effects. Most are mild to moderate and transient and it will decrease with continued treatment. Please consult your doctor if the symptoms are severe.
  • Hypoglycemia (low blood sugar): Hypoglycemia has been reported in patients with type 2 diabetes. If you experience strong hunger, fatigue, cold sweats, tremors, palpitations, or fever, take 10g of sugar or 100mL of juice containing sugar and rest. Please make sure that no hypoglycemic symptoms occur before driving a car, operating machinery, or working at height.
  • Acute pancreatitis (0.1%): Seek urgent medical attention if symptoms such as severe abdominal pain, back pain, vomiting, or fever occur.
  • Cholelithiasis (gallstones), cholecystitis (inflammation of the gallbladder), cholangitis (inflammation of the bile ducts), obstructive jaundice.,frequency unknown: abdominal pain may occur after a greasy meal or at the night after overeating. In acute pancreatitis caused by gallstones, the pain begins abruptly and is maximal within minutes. Elevated amylase and lipase are not predictive of the development of pancreatitis, but they are diagnostic indicators when symptoms are present. Seek urgent medical attention if you experience severe abdominal pain.
  • Anaphylactic shock/angioedema: An overreaction of immune response (allergic reaction) may cause symptoms such as decreased blood pressure, fainting, edema of the face, lips, and skin, rash, and difficulty breathing due to edema of the airways. If anaphylactic symptoms occur, call an ambulance immediately because injection treatment at a hospital is necessary.
  • Medullary thyroid carcinoma: In a 2-year carcinogenicity study in rats and mice using subcutaneous semaglutide, an increased incidence of thyroid C-cell tumors was reported in the patients with usual or lower dose of Rybelsus treatment.

About Rybelsus treatment and pregnancy

Rybelsus cannot be used during pregnancy or lactation. Please discontinue use at least 2 months before starting pregnancy preparation. There have been no reports of effects on male fertility.

If diarrhea or vomiting persists during taking Rybelsus, the absorption of warfarin may be impaired. Avoid combined use with thyroid hormone (thyradin, Levothyroxine Sodium Hydrate). Severe hypoglycemia has been reported when combing with insulin and other diabetic medications. Do not use diabetic medications as diet pills concomitantly if you are prescribed from another hospital. There are no interactions with orlistat (Xenical), although safety with other anti-obesity drugs and diet herbs has not been established.

Although there is no direct interaction between Rybelsus and alcohol, excessive alcohol consumption inhibits glycogen production and glycogenesis in the liver and can cause hypoglycemia alone. Excessive alcohol consumption should be avoided during Rybelsus treatment.

Fees(Tax included)

Fees (Tax included)
Consultation feeFirst visit ¥3,850
Revisit ¥1,650
Rybelsus 3mg30tablets
Rybelsus 7mg30tablets
Rybelsus 14mg30tablets
Blood test ¥3,982
Urine test¥1,056

※ A medical examination is required for a prescription. An additional consultation fee will apply.
※ Blood tests are required at the first visit and once every 3 months thereafter for side effects check.

List of references/websites
  1. O’Neil PM, Birkenfeld AL, McGowan B, Mosenzon O, Pedersen SD, Wharton S, Carson CG, Jepsen CH, Kabisch M, Wilding JPH. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2. Epub 2018 Aug 16. PMID: 30122305.
  2. Davies M, Pieber TR, Hartoft-Nielsen ML, Hansen OKH, Jabbour S, Rosenstock J. Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA. 2017 Oct 17;318(15):1460-1470. doi: 10.1001/jama.2017.14752. PMID: 29049653; PMCID: PMC5817971.
  3. M.S. Capehorn, A.-M. Catarig, J.K. Furberg, A. Janez, H.C. Price, S. Tadayon, B. Vergès, M. Marre, Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10), Diabetes & Metabolism, Volume 46, Issue 2, 2020, Pages 100-109, ISSN 1262-3636, https://doi.org/10.1016/j.diabet.2019.101117. (https://www.sciencedirect.com/science/article/pii/S1262363619301326)
  4. ノボノルディスクファーマ株式会社 2型糖尿病治療剤 経口GLP-1受容体作動薬 セマグルチド(遺伝子組換え)リベルサス錠3mg リベルサス錠7mg リベルサス錠14mg 2021年9月改定(第2版)
  5. MSD Connect リベルサス 作用機序 https://www.msdconnect.jp/products/rybelsus/action_mechanism.xhtml 最終アクセス 2021/11/27.
  6. Ottney A. Glucagon-like peptide-1 receptor agonists for weight loss in adult patients without diabetes. Am J Health Syst Pharm. 2013 Dec 1;70(23):2097-103. doi: 10.2146/ajhp130081. PMID: 24249759.
  7. Aroda VR, Rosenstock J, Terauchi Y, Altuntas Y, Lalic NM, Morales Villegas EC, Jeppesen OK, Christiansen E, Hertz CL, Haluzík M; PIONEER 1 Investigators. PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes. Diabetes Care. 2019 Sep;42(9):1724-1732. doi: 10.2337/dc19-0749.
  8. Gibbons C, Blundell J, Tetens Hoff S, Dahl K, Bauer R, Baekdal T. Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes. Diabetes Obes Metab. 2021 Feb;23(2):581-588. doi: 10.1111/dom.14255. Epub 2020 Nov 27. PMID: 33184979; PMCID: PMC7839771.
  9. Yamada Y, Katagiri H, Hamamoto Y, Deenadayalan S, Navarria A, Nishijima K, Seino Y; PIONEER 9 investigators. Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial. Lancet Diabetes Endocrinol. 2020 May;8(5):377-391. doi: 10.1016/S2213-8587(20)30075-9. PMID: 32333875.
  10. Yabe D, Nakamura J, Kaneto H, Deenadayalan S, Navarria A, Gislum M, Inagaki N; PIONEER 10 Investigators. Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2020 May;8(5):392-406. doi: 10.1016/S2213-8587(20)30074-7. PMID: 32333876.
  11. Rosenstock J, Allison D, Birkenfeld AL, Blicher TM, Deenadayalan S, Jacobsen JB, Serusclat P, Violante R, Watada H, Davies M; PIONEER 3 Investigators. 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 Apr 16;321(15):1466-1480. doi: 10.1001/jama.2019.2942. PMID: 30903796; PMCID: PMC6484814.
  12. Rodbard HW, Rosenstock J, Canani LH, Deerochanawong C, Gumprecht J, Lindberg SØ, Lingvay I, Søndergaard AL, Treppendahl MB, Montanya E; PIONEER 2 Investigators. Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial. Diabetes Care. 2019 Dec;42(12):2272-2281. doi: 10.2337/dc19-0883. Epub 2019 Sep 17. PMID: 31530666.
  13. Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, Jeppesen OK, Lingvay I, Mosenzon O, Pedersen SD, Tack CJ, Thomsen M, Vilsbøll T, Warren ML, Bain SC; PIONEER 6 Investigators. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2019 Aug 29;381(9):841-851. doi: 10.1056/NEJMoa1901118. Epub 2019 Jun 11. PMID: 31185157.

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