Rybelsus
Rybelsus Uses, Dosage, Side Effects, Food Interaction and all others data.
Rybelsus is a glucagon-like peptide 1 (GLP-1) analog used to manage type 2 diabetes along with lifestyle changes, such as dietary restrictions and increased physical activity. Other members of this drug class include Exenatide and Liraglutide. Rybelsus was developed by Novo Nordisk and approved by the FDA for subcutaneous injection in December 2017. The tablet formulation was approved for oral administration in September 2019. Rybelsus works by binding to and activating the GLP-1 receptor, thereby stimulating insulin secretion and reducing blood glucose.
The subcutaneous injection is administered once weekly and the tablet is administered once a day. Rybelsus offers a competitive advantage over other drugs used to manage diabetes, which may require several daily doses. Clinical trials have determined that this drug reduces glycosylated hemoglobin (HbA1c) levels and reduces body weight, proving to be effective for patients with type 2 diabetes. In June 2021, semaglutide was approved by the FDA for chronic weight management in adults with general obesity or overweight who have at least one weight-related condition: this marks semaglutide as the first approved drug for such use since 2014.
Rybelsus reduces HbA1c, systolic blood pressure, and body weight. After 12 weeks of treatment, semaglutide decreased fasting and postprandial glucose by increasing insulin production and decreasing glucagon secretion (which is normally associated with increases in blood sugar). Rybelsus also lowers fasting triglycerides and VLDL cholesterol, exerting beneficial effects on cardiovascular health.
| Trade Name | Rybelsus |
| Availability | Prescription only |
| Generic | Semaglutide |
| Semaglutide Other Names | Semaglutide, Sémaglutide |
| Related Drugs | Farxiga, Praluent, Repatha, metformin, Xarelto, simvastatin, Brilinta, Ozempic, Trulicity, phentermine |
| Weight | 14mg, 3mg, 7mg, 2mg/1.5ml(0.25mgor0.5mgdose, 1mgdose, |
| Type | Oral tablet, subcutaneous solution, 2 mg/1.5 ml, 4 mg/3 ml) |
| Formula | C187H291N45O59 |
| Weight | Average: 4113.641 Monoisotopic: 4111.11537713 |
| Protein binding | Semaglutide binds with high affinity to plasma albumin, promoting high levels of drug stability. It is more than 99% bound to albumin. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | Novo Nordisk Limited |
| Available Country | Canada, United Kingdom, United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Rybelsus is a glucagon-like peptide 1 receptor agonist used to improve glycemic control in type 2 diabetes mellitus.
Rybelsus is indicated to improve glycemic control in adults diagnosed with type 2 diabetes mellitus, and is used as an adjunct to diet and exercise. However, semaglutide is not a suitable first-line drug for diabetes that has not been controlled by diet and exercise. In addition, it has not been studied in patients with pancreatitis. Rybelsus is not intended for use in patients with type 1 diabetes or to treat diabetic ketoacidosis.
Rybelsus is indicated for chronic weight management in adults with obesity or overweight with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol), for use in addition to a reduced-calorie diet and increased physical activity.
Rybelsus is also used to associated treatment for these conditions: BMI >27 kg/m2, BMI >30 kg/m2, Type 2 Diabetes Mellitus, Chronic Weight Management
How Rybelsus works
Mechanism of glycemic control
GLP-1 is a physiological hormone that promotes glycemic control via several different mechanisms, including insulin secretion, slowing gastric emptying, and reducing postprandial glucagon secretion. The homeostasis of glucose is dependent on hormones such as insulin and amylin, which are secreted by the beta cells of the pancreas. Rybelsus is 94% similar to human GLP-1. Analogs of this hormone such as semaglutide stimulate the synthesis of insulin by stimulating pancreatic islet cells and reducing glucagon secretion. They directly bind with selectivity to the GLP-1 receptor, causing various beneficial downstream effects that reduce blood glucose in a glucose-dependent fashion.
Mechanism of cardiovascular benefit and weight loss
In hypercholesterolemia, semaglutide is believed to reduce the progression of atherosclerosis via decreased gut permeability and decreased inflammation. Weight loss is believed to occur via the reduction of appetite and food cravings after semaglutide administration.
Toxicity
Overdoses of up to 4 mg in one ingestion have been reported, with nausea being the most commonly reported symptom. All patients in clinical trials who experienced an overdose recovered fully. Appropriate supportive care should be given according and dictated by the patient's condition. Prolonged observation and treatment may be required, as the half-life of this drug is about one week. There is no antidote to an overdose with semaglutide.
Food Interaction
- Take on an empty stomach. For oral use of semaglutide, take 30 minutes before the first meal of the day.
- Take with plain water. For oral use of semaglutide, do not exceed 4 ounces of water (1/2 cup).
[Moderate] MONITOR: Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists delay gastric emptying, which may impact the absorption of concomitantly administered oral medications.
Mild to moderate decreases in plasma concentrations of coadministered drugs have been demonstrated in pharmacokinetic studies for some GLP-1 receptor agonists (e.g., exenatide, lixisenatide), but not others.
The impact of dual GLP-1 and GIP receptor agonist tirzepatide on gastric emptying was reported to be greatest after a single dose of 5 mg but diminished after subsequent doses.
According to the prescribing information, liraglutide did not affect the absorption of several orally administered drugs to any clinically significant extent, including acetaminophen, atorvastatin, digoxin, griseofulvin, lisinopril, and an oral contraceptive containing ethinyl estradiol-levonorgestrel.
Likewise, no clinically relevant effect on absorption was observed for concomitantly administered oral drugs studied with albiglutide (digoxin, ethinyl estradiol-norethindrone, simvastatin, warfarin), dulaglutide (acetaminophen, atorvastatin, digoxin, ethinyl estradiol-norelgestromin, lisinopril, metformin, metoprolol, sitagliptin, warfarin), or semaglutide (atorvastatin, digoxin, ethinyl estradiol-levonorgestrel, metformin, warfarin).
In addition, coadministration of acetaminophen after a first dose of tirzepatide 5 mg reduced the acetaminophen peak plasma concentration (Cmax) by 50% and delayed its median time to peak plasma concentration (Tmax) by 1 hour, but no significant impact on Cmax and Tmax was observed after coadministration at week 4, and the overall exposure of acetaminophen was unaffected.
Nevertheless, potential clinical impact on other oral medications cannot be ruled out, particularly those with a narrow therapeutic index or low bioavailability, those that depend on threshold concentrations for efficacy (e.g., antibiotics), and those that require rapid gastrointestinal absorption (e.g., hypnotics, analgesics).
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MANAGEMENT: Pharmacologic response to concomitantly administered oral medications should be monitored more closely following the initiation or discontinuation of treatment with a GLP-1 receptor agonist or a dual GLP-1 and GIP receptor agonist.
Rybelsus Alcohol interaction
[Moderate] GENERALLY AVOID:
Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes.
Hypoglycemia most frequently occurs during acute consumption of alcohol.
Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise.
The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia.
Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion.
By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia.
[Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes.
A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.
Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis.
Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan.
Alcohol should not be consumed on an empty stomach or following exercise.
Rybelsus Drug Interaction
Moderate: insulin glargine, albuterolUnknown: aspirin, aspirin, diphenhydramine, ubiquinone, rosuvastatin, duloxetine, empagliflozin, escitalopram, atorvastatin, pregabalin, metoprolol, metoprolol, cyanocobalamin, ascorbic acid, cholecalciferol, alprazolam, zinc sulfate, cetirizine
Rybelsus Disease Interaction
Major: suicidal behavior and ideation, thyroid cancerModerate: GI adverse events, hypoglycemia, pancreatitis, retinopathy
Volume of Distribution
The volume of distribution of semaglutide is 8L to 9.4L. It crosses the placenta in rats.
Elimination Route
The Cmax of semaglutide was 10.9 nmol/L, with AUC of 3123.4 nmol h/L and a Tmax of 56 h in one clinical trial, achieved within 1-3 days. The absolute bioavailability is 89%. Steady-state concentration of the oral tablet is achieved in 4-5 weeks. Average steady state concentrations of semaglutide are the mean steady state concentrations after dosing at 0.5mg to 1mg range from 16 nmol/L to 30 nmol/L.
Half Life
One of the major properties of semaglutide is its long half-life of 168 h. The long half-life is attributed to its albumin binding. This lowers the renal clearance and protects semaglutide from metabolic breakdown.
Clearance
The clearance rate of semaglutide is 0.039 L/h according to one clinical study. On the FDA label, semaglutide clearance is reported to be about 0.05 L/h in patients with type 2 diabetes mellitus.
Elimination Route
This drug is mainly cleared by the kidneys, and is found excreted in both the urine and feces. The main elimination route is the urine by corresponding to 53% of an ingested radiolabeled dose, with 18.6% found in the feces. A smaller amount of 3.2% was found to be exhaled. Hepatic impairment does not appear to affect the clearance of this drug and dose adjustments are not required in patients with decreased liver function.
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