Rybelsus, Wegovy, Ozempic Vs Orlistat (Semaglutide Vs Xenical)

Ozempic Vs Orlistat compares the weight loss effects of the two drugs. Ozempic is approved primarily for the treatment of diabetes, however, its higher dose formulation, Weogvy, is FDA-approved for obesity. Hence, Ozempic is also associated with significant weight loss.

Semaglutide is a novel GLP-1 analog indicated for the treatment of diabetes and obesity. Orlistat is only indicated for the treatment of obesity.

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What is Semaglutide?

Semaglutide is a GLP-1 analog that acts as endogenous incretin. Incretins are hormones that come from the acronym “INTestinal SeCRETion of IN“Sulin”.

Incretins are hormones released when there is a glucose load. GLP-1 (Glucagon-like peptide, and Gastric inhibitory peptide) is the most common endogenous incretins.

Rybelsus is an oral formulation of Semaglutide. It is approved for the treatment of diabetes type 2.

Ozempic, like Wegovy, is a once-weekly injectable formulation of Semaglutide. It is approved for the treatment of Type 2 Diabetes. However, Ozempic is also associated with significant weight loss in diabetic individuals.

Wegovy is a GLP-1 analog. It is the brand name of Semaglutide injection administered once a week. Recent clinical trials have shown the superiority of Wegovy over most of the FDA-approved weight-loss drugs including Orlistat (Xenical).

Most drugs used for weight loss in the past are not used nowadays. Physicians are not comfortable risking their patients’ health for a weight loss of just a few pounds.

Lorcaserin (Belviq) has already been removed from the market because of the drug’s cancer-causing potential.

The maximum weight loss observed with all the weight loss medicines does not exceed 10%. Wegovy on the other hand has been observed to cause a weight loss of up to 16%.

Furthermore, the weight loss effect of the drug is maintained when Wegovy is continued for one to two years.

Semaglutide: Rybelsus, Ozempic, and Wegovy

Semaglutide is indicated for treating diabetes as well as obesity. Among the 3 formulations, Wegovy is the only one approved for weight loss.

Wegovy is more effective than other weight-loss drugs. It provides you with more sustained weight loss. Rybelsus and Ozempic have been approved for treating diabetes. Ozempic is the second most potent diabetes drug approved.

Studies have shown that while most weight loss drugs used in clinical trials offer some short-term results, they tend to be less effective over the long haul.

Second, it suppresses hunger. This is why you need to make sure you are able to keep the appetite suppressed while you are using the Semaglutide drug. Third, it has few side effects compared to other oral medications.

What is Rybelsus, Ozempic, and Wegovy?

The three Semaglutide formulations are Rybelsus, Ozempic, and Wegovy.

What is Rybelsus?

Rybelsus, an oral form of Semaglutide, is used to treat diabetes. You can take it orally at a dose of 3, 7, and 14 mg per day. It is often combined with insulin or other anti-diabetic medications and used as an adjunct to exercise and diet.

Clinical trials have shown that oral Semaglutide can reduce glycated hemoglobin by about 1.3%. Dose-dependent, the glucose-lowering effect of oral Semaglutide is also possible.

In the treatment of Obesity, Rybelsus has been found to cause a weight loss of approximately 8.1 pounds after 26 weeks.

“Rybelsus reduces HbA1C by 1.3% and cause a weight loss of 8 pounds”

What is Ozempic?

Ozempic, a Semaglutide injectable formulation, is what you will see. It can be administered subcutaneously once a week.

You can get it in either 0.5 mg or 1 mg doses. It can be used as an adjunct to exercise and diet for diabetes treatment.

Ozempic was shown to decrease glycated hemoglobin levels from 1.2% to 1.8%. Ozempic has caused a weight loss of about 13 pounds when administered at doses of 0.5 mg – 1 mg per week.

What is Wegovy?

It is a high-dose injectable Semaglutide administered once a week in a dose of 2.4 mg. It got recent FDA approval for the treatment of obesity and overweight in patients who have at least one weight-related condition such as diabetes, high cholesterol levels, or hypertension [Ref].

After four large, randomized clinical trials that confirmed its safety and effectiveness, FDA approved Wegovy for weight management and obesity.

Read: The Steps Trials

Side Effects of Semaglutide:

The first disadvantage of Semaglutide is its price. The tablet formulation, Rybelsus, costs USD 30.90 per tablet. The weekly injection costs more than USD 300 per injection.

Furthermore, most insurance companies might not include Wegovy in their list of medications simply for losing weight.

Although obesity is called the mother of most illnesses, it is not considered to be life-threatening.

The second disadvantage of Semaglutide is its side effects. It has been associated with medullary thyroid cancer and MEN 2 syndrome.

It can cause inflammation of the pancreas, kidney injury, gastrointestinal side effects, and gallbladder disease.

The gastrointestinal side effects affect most individuals and can manifest as bloating, heartburn, excessive abdominal gases, nausea, constipation, and altered bowel habits.

Semaglutide has also been associated with worsening symptoms of diabetes-related eye disease (Diabetic retinopathy). lastly, the fear of injection and injection-related side effects are always there.

Conclusion:

Given the long time-course and the long-term usage of glucagon-like peptide-1 (GLP-1), long-term persistence and maintenance of blood glucose levels can be achieved.

This provides a good basis for better metabolic control and improved glycemic control which can possibly lead to a reduction in body weight. GLP-1 analogs have been well tolerated even in high doses of 2.4 mg per week injections (Wegovy).

Orlistat (Xenical):

Orlistat or Xenical is a drug that inhibits the absorption of dietary fats. It is primarily used to treat obese and overweight individuals.

What is Orlistat (Xenical, Alli)

Orlistat or Xenical is a drug that inhibits the absorption of dietary fats. It is primarily used to treat obese and overweight individuals.

Side effects of Orlistat or Xenical include nausea, vomiting, abdominal cramping, bloating, constipation, sleepiness, and vomiting.

The Pros and Cons of Xenical (Orlistat):

The pros of Xenical are obvious. It is safer than any other fat-loss drug. It has minimal side effects and is more safe than most other diet pills. In fact, the low-dose Orlistat can also be bought as an OTC diet pill for weight loss.

The only downside to Xenical is the fact that it does not work for everyone. It is best for people who consume a lot of fats and oils.

People who consume less dietary fat may not benefit from taking Orlistat. Furthermore, most people lose some weight during their initial treatment days but start gaining weight again after some time.

The relapse rate is higher compared to Wegovy, a novel injectable diabetes medicine intended for weight loss in morbidly obese individuals.

Xenical (Orlistat) should be taken only with food. Xenical is taken with the first bolus of each meal (twice or thrice daily depending on the number of meals per day).

Xenical (Orlistat) causes significant gastrointestinal side effects. It causes the deficiency of fat-soluble vitamins and supplementation with fat-soluble vitamins is usually recommended especially with long-term treatment.

Recently, the FDA issued a Black Box warning with Orlistat. More than 30 cases of severe liver injury have been reported.

Patients should be cautious and report any new onset of symptoms such as abdominal pain, nausea, jaundice, or altered sleep pattern after treatment initiation.

How effective is Xenical (Orlistat)?

It is not a magic pill to lose weight quickly. The short-term weight loss will depend upon the patient’s metabolic response to the drug.

The weight loss with Xenical is variable. It has been estimated to cause a weight loss of 3.05 kg vs. 1.9 kg with a placebo medicine; P <.001 after 6 months of treatment.

Most weight loss physicians are not happy with just a 3 kg weight loss. A 120 kgs person losing weight of just 3 kg is nothing.

However, when combined with other weight-losing therapies and lifestyle modification, the results could be amplified.

Other studies have observed a weight loss of 5 – 10% with orlistat when combined with extensive lifestyle intervention.

Conclusion:

Given the long time-course and the long-term usage of glucagon-like peptide-1 (GLP-1), long-term persistence and maintenance of blood glucose levels can be achieved.

This provides a good basis for better metabolic control and improved glycemic control which can possibly lead to a reduction in body weight. GLP-1 analogs have been well tolerated even in high doses of 2.4 mg per week injections (Wegovy).

Ozempic Vs Orlistat: Pharmacokinetics

Rybelsus and Ozempic Vs Orlistat: Effect on Blood Glucose:

Orlistat is not a medicine used to treat diabetes. However, when you lose weight and when you are not able to absorb dietary calories from fats, your blood glucose may not spike after meals. 

In clinical trials, Orlistat was observed to cause a reduction in A1C by about 0.5% [Ref]. Semaglutide, on the other hand, is the second most potent diabetes drug. It is associated with an A1C reduction of -1.2% to -1.8%.

Semaglutide Vs Orlistat: Effect on Bodyweight:

The average weight loss after 6 months to a year of taking Semaglutide ranges from 7 to 16 %. Rybelsus use is associated with about 7 to 10% weight loss, Ozempic with 9 to 12%, while Wegovy is associated with up to 16% body weight loss.

Compared to Semaglutide (Rybelsus, Ozempic, and Wegovy), Orlistat (Xenical) use is associated with about 5% to 10% weight loss only.

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