Rybelsus® vs. Metformin: Which Medication Suits You Better?

Rybelsus® is the brand name for oral Semaglutide, the first and currently only oral glucagon-like peptide-1 (GLP-1) medication approved for blood sugar control in adults with Type 2 Diabetes Mellitus. Oral Semaglutide also has significant weight-reducing benefits.¹

However, these attributes aren’t unique to Semaglutide. With the brand-name medication being unaffordable to many, cheaper alternatives are currently being explored. One of them is the old drug Metformin. Thus, the Rybelsus® vs. Metformin comparison has now become a hot internet topic.

Metformin is a first-line diabetes medication with various other indications in both children and adults.² It’s widely prescribed due to its therapeutic and cost advantages.³ Studies also show that Metformin can make people lose weight.⁴ The question is: How does it compare with oral Semaglutide?

This article compares the oral medications Semaglutide and Metformin in terms of their efficacy, risks, cardiovascular benefits, and accessibility. We’ll also debunk some common misconceptions about oral Semaglutide and explain how Henry Meds can help you get a compounded version of this medication affordably, sustainably, and safely.

What Is Oral Semaglutide, and How Does It Work?

Semaglutide is a medication belonging to the glucagon-like peptide-1 (GLP-1) receptor agonist class. It mimics the natural human gut hormone GLP-1, which stimulates your pancreas to enhance insulin release and restrict glucagon secretion. This dual action lowers blood sugar levels.⁵

GLP-1 also slows down digestion and suppresses appetite, reducing caloric intake and body weight. However, GLP-1 stays effective for only a few minutes. Semaglutide, which stays longer in the body, amplifies GLP-1’s effects — leading to better blood sugar and weight management.⁵

Semaglutide was initially available only as an injectable owing to the challenges of absorbing protein-like medications, such as this GLP-1 agonist, in the gut. Scientific advancements have led to the development of the tablet form, making this medication easier for some patients to take.⁶

Henry Meds compounds both an oral and a sublingual version. Sublingual Semaglutide is taken by mouth and absorbed under the tongue, bypassing the limitations of intestinal absorption like strict timing of intake.

What Is Metformin, and How Does It Work?

Metformin belongs to a class of drugs referred to as “biguanides,” also proven effective in blood sugar management. A cornerstone of Type 2 Diabetes management, Metformin helps regulate your blood sugar levels in several ways:²

• Metformin decreases how much sugar your intestines absorb after meals.

• This biguanide limits the amount of sugar (specifically, glucose) your liver releases into the bloodstream.

• Metformin improves how your cells respond to insulin — or insulin-sensitivity — promoting glucose entry into the cells and decreasing blood glucose. This effect is most pronounced in the muscles and fat cells, where the body’s energy consumption and storage mechanisms are most active.

Of these actions, insulin sensitivity enhancement is the biggest contributor to Metformin’s ability to curb blood sugar spikes and reduce weight.⁴

Is Oral Semaglutide Better Than Metformin?

To know whether oral Semaglutide or Metformin is better, we must compare them on various clinical aspects. Patient factors must also be considered.

Is Oral Semaglutide or Metformin Better for Weight Loss in People Without Type 2 Diabetes Mellitus?

For adults with weight loss resistance without Type 2 Diabetes Mellitus, clinical trials reveal that high-dose brand-name oral Semaglutide daily with lifestyle modifications can cause weight loss of as much as 15.1% after 68 weeks of treatment.⁷ Meanwhile, a maximum daily dose of Metformin was shown to cause modest weight loss, reducing body weight by 5.6% after six months — with reduced evening caloric consumption but little physical activity change.⁴

Both medications can influence weight. However, oral Semaglutide delivered greater weight loss in a longer study, suggesting potentially stronger and sustained effects.

Is Oral Semaglutide or Metformin Better for Weight Loss in Patients with Type 2 Diabetes Mellitus?

Both oral Semaglutide and Metformin are used for blood sugar management in Type 2 Diabetes, but their impact on blood sugar levels differs.

In studies of patients with Type 2 Diabetes, daily intake of low doses of brand-name oral Semaglutide significantly lowered HbA1c, a measure of long-term blood sugar control, by as much as 1.1% from initial levels after 26 weeks of treatment. Additionally, participants lost about 5 pounds (2.3 kg) on average during this period.⁸ This suggests that the GLP-1 receptor agonist is highly effective in improving blood sugar levels and weight over long periods.

By comparison, daily near-maximum doses of Metformin can reduce HbA1c by as much as 2.0% after 14 weeks.⁹ Additionally, a maximum daily dose of Metformin can lead to a 6 pound (2.7 kg) body weight reduction after 16 weeks.¹⁰

On the surface, it may seem that Metformin has advantages over oral Semaglutide. However, progressive decline in insulin production in longstanding Type 2 Diabetes Mellitus reduces this medication’s effectiveness over time, making it necessary to switch to other Diabetes drugs or combine it with another.¹¹ Research shows that combining Metformin with brand-name Semaglutide can enhance the biguanide’s effects when they’re beginning to level off or wane.¹²

Oral Semaglutide vs. Metformin: Which Protects You Better from Heart Disease?

In clinical trials, brand-name Semaglutide tablets produced the following indirect cardiovascular benefits:¹³

• Reduced body weight

• Healthy blood pressure levels

• Enhanced blood sugar control

• Improved lipid levels

Also importantly, this GLP-1 receptor agonist produced direct heart-protective benefits, particularly lower risk of nonfatal heart attack and stroke, hospitalization from heart failure, and death from heart disease.¹³

On the other hand, the more established oral Diabetes medication Metformin is known to improve lipid levels and prevent heart enlargement and failure in patients with blood sugar control issues.¹⁴

Cardiovascular improvement comes with weight loss of at least 5-10%.¹⁵ As previously stated, both medications can make individuals lose at least 5% of their body weight. However, intake must be combined with lifestyle modifications, including a healthy diet and regular exercise.

How Do You Take Semaglutide and Metformin Tablets?

Patients need to take one brand-name Semaglutide tablet per day as soon as they wake up. The medication should be taken on an empty stomach, with up to 4 ounces or 120 mL of water. Patients should wait for at least 30 minutes before eating food or taking other drugs, which can impair Semaglutide absorption.¹⁶

Henry Meds’ oral Compounded Semaglutide may be taken the same way. Oral Compounded Semaglutide is available for patients who prefer this route due to familiarity and ease of storage. Meanwhile, sublingual Compounded Semaglutide is an alternative that doesn’t need strict timing because it’s absorbed under the tongue, not the gut. Both forms have their advantages. Whichever you prefer, your clinician will give you instructions for proper intake.

On the other hand, short-acting Metformin is taken at doses of 500 mg twice daily (a low dose). Metformin 500-mg extended-release tablets may be taken once a day. The safety of extended-release Metformin in children has not been determined. Both Metformin preparations may be taken with meals.¹⁷

What Conditions Can Oral Semaglutide and Metformin Treat?

Oral Semaglutide has been approved by the US FDA as an adjunct to diet and exercise for managing blood sugar levels in adults with Type 2 Diabetes Mellitus.¹⁸ Meanwhile, Metformin is the preferred first-line medication for Type 2 Diabetes in both adults and children 10 years and older. Metformin is also used off-label for weight management and treating prediabetes, and polycystic ovary syndrome, among other conditions.¹⁹

What Are the Side Effects of Oral Semaglutide and Metformin?

Brand-name oral Semaglutide’s most common side effects frequently involve the digestive system. The symptoms include nausea, vomiting, and diarrhea.²⁰

Rare but serious adverse effects have been documented in studies after intake of brand-name Semaglutide. These side effects include the following:²⁰

• Hypoglycemia (severely low blood sugar levels)

• Back and joint pain

• Infection

• Acute gallbladder disease

• Increased heart rate

• Acute pancreatitis

• Allergic reaction

• Acute kidney failure

• Visual blurring in adults with Type 2 Diabetes Mellitus

• Medullary thyroid cancer and a related cancer syndrome, multiple endocrine neoplasia type 2

However, those who reported such adverse events already had pre-existing medical conditions before starting the treatment. Careful patient selection can prevent these potential side effects.²⁰

Possible drug interactions may arise when brand-name Semaglutide pills are taken alongside other Diabetes medications like insulin, causing severe hypoglycemia in some patients.²⁰ Other oral drug treatments that must be taken on the same schedule as Semaglutide tablets, such as thyroid and osteoporosis medications, can also produce drug interactions.²¹ However, Henry Meds’ sublingual Compounded Semaglutide lets you avoid this problem.

Overdosing on Semaglutide may result in more gastrointestinal symptoms. Notably, two cases of nausea, vomiting, and abdominal pain after tenfold dosing with Semaglutide have been reported.²²

Metformin, on the other hand, may cause gastrointestinal side effects in up to a third of patients, including dyspepsia, diarrhea, heartburn, abdominal pain, bloating, metallic taste, nausea, vomiting, and eating disorders. Vitamin B12 malabsorption, deficiency, or both may also occur.²

When taken alone, Metformin does not cause blood sugar to drop below normal levels. However, it may dangerously enhance the blood glucose-lowering effects of insulin and other drugs for Diabetes.²

Severe lactic acidosis can result from acute Metformin overdose or in patients with severely compromised kidney function.² Lactic acidosis is a potentially life-threatening condition wherein lactic acid accumulates in the bloodstream and weakens the heart.²³ However, there is no evidence that lactic acidosis occurs with Metformin intake at the usual doses.²

How Much Do Oral Semaglutide and Metformin Cost?

Brand-name oral Semaglutide packs a punch in terms of its therapeutic benefits, but its price tag can be hefty at $935.77 per month.²⁴ In contrast, Metformin, a well-established treatment for Type 2 Diabetes, offers a much friendlier option at around $44.20 ($34.50-$60.80) for a 30-day supply.²⁵ Metformin has lower-cost generic forms, unlike brand-name oral Semaglutide.

However, cost shouldn't overshadow your health goals. You can stay compliant with your weight management regimen when you subscribe to Henry Meds’ affordable services. Our treatment programs can help you gain affordable, safe, and sustainable access to the tablet or sublingual Compounded Semaglutide, which have the same health-promoting advantages as brand-name oral Semaglutide.

What Is the Disadvantage of Brand-Name Oral Semaglutide Compared to Metformin?

The cost of brand-name Semaglutide pills may hinder patients from accessing this medication. By comparison, anyone with a valid doctor’s prescription can find generic Metformin at most pharmacies for a fraction of the cost.

However, as mentioned, clinical research shows that oral Semaglutide is more effective than older medications in body weight and blood sugar management. Semaglutide may be prescribed together with Metformin if the biguanide begins to lose effectiveness.

Ultimately, the choice depends on your individual needs, budget, and healthcare professional's recommendations. If you’re already subscribed to one of Henry Meds’ weight management programs, the providers on our platform can help you choose the most suitable option.

How Can Henry Meds Help You Stay Compliant with Your Weight Management Regimen?

Pharmaceutical compounding is the process of customizing a medication to meet a patient's needs. Compounded medicines remain easily accessible when branded prescription medications become scarce. Licensed pharmacists can skillfully compound medications to a form that is easier to take and has the right dosage.²⁶

In January 2024, the net price after discounts of a month’s worth of branded GLP-1 agonists like Semaglutide reached as high as $761.²⁷ Meanwhile, Henry Meds’ GLP-1 treatment programs, which can make Compounded Semaglutide accessible to suitable patients, cost only $249 without hidden fees.

The Henry Meds platform links you to a network of licensed healthcare providers you can consult online for your weight management concerns. They will prescribe tablet or sublingual Semaglutide if it’s suitable for you.

Henry Meds also connects you with compounding pharmacies licensed by the FDA and the state Boards of Pharmacy, and US board-certified pharmacists who can make a version of this GLP-1 medication with the right dose and form. They can also have it delivered conveniently to your doorstep.

No need to worry about medication shortages and high costs. Have peace of mind in knowing that US-licensed medical professionals are overseeing your therapy. Henry Meds can make your health journey easier, more affordable, and more sustainable. 

Oral Semaglutide vs. Metformin: The Bottom Line

Oral Semaglutide and Metformin are FDA-approved medications that can effectively lower blood sugar and body weight and produce heart-healthy benefits. At first glance, Metformin may have certain advantages over oral Semaglutide. However, this old prescription medicine can lose its effectiveness over time, while oral Semaglutide’s actions are sustained over long periods.

It may also seem at first that Metformin offers more value for your money than oral Semaglutide. However, this biguanide’s waning effects can make it cost-ineffective as time passes. Meanwhile, oral Semaglutide’s price challenges can easily be addressed by pharmacological compounding.

Henry Meds gives you access to a wide network of US-licensed medical practitioners and pharmacists and compounding pharmacies that are licensed by the FDA and the state Boards of Pharmacy. Our weight management programs can make Compounded Semaglutide available to you at a more  affordable cost if the medication is suitable for you. Begin your weight loss journey and receive the treatment you deserve by making an appointment with us today.

FAQs

Is Oral Semaglutide Recommended as the First-Choice Medicine for Treating Diabetes?

Semaglutide has proven effective in controlling blood sugar levels and body weight. Studies show that it’s superior to non-GLP-1 agents and the once-daily GLP-1 medication Liraglutide.²⁸ Given these findings, the FDA authorized a label update in 2023 that allowed adults with Type 2 Diabetes Mellitus to use oral Semaglutide as a first-line medication for blood glucose control.²⁹

However, it’s important to remember the following about oral Semaglutide:

• Oral Semaglutide is not a one-size-fits-all solution. Your healthcare provider considers your individual needs, medical history, and current medications before recommending the best treatment plan.

• Potential side effects and medication interactions can make oral Semaglutide unsuitable for some individuals.

• Cost and insurance plans can be factors. Brand-name oral Semaglutide can be expensive, and insurance coverage may vary.³⁰

Ultimately, the best medication that combines both weight management and Diabetes treatment is personalized and tailored to your specific needs. Talk to your provider on the Henry Meds platform to understand all available options and determine the right approach to managing your medical condition effectively.

Does Oral Semaglutide Lower Blood Sugar Immediately?

Oral Semaglutide does not offer an immediate blood sugar drop like an insulin injection. However, it can lower blood sugar levels over time. This GLP-1 medication stimulates insulin secretion and prevents the release of insulin’s antagonistic hormone glucagon.

The sustained effect of oral Semaglutide lowers HbA1c, a measure of blood sugar control over three months. Research on brand-name oral Semaglutide demonstrates significant blood glucose reductions after consistent intake.⁸

Is Oral Semaglutide a High-Risk Medication?

Oral Semaglutide offers impressive benefits, but like most medications, it's not without potential risks. The most commonly reported adverse effect of this GLP-1 agonist is gastrointestinal disturbance, which usually gets better over time.

Serious side effects are rare but have been reported in clinical trials on brand-name oral Semaglutide. These risks can be prevented or mitigated through the following measures:

• Careful patient screening: Identifying individuals who may be more susceptible to certain side effects, e.g. Diabetes-related eye conditions like diabetic retinopathy, can help avoid such risks altogether.²⁰

• Close monitoring: Regular consultations with your healthcare provider can help detect any potential issues early on.³¹

• Dose adjustments: If needed, your doctor can adjust your oral Semaglutide dose to minimize the risk of side effects while still achieving its benefits.³¹

Importantly, the decision to take any medication is one you should make with your healthcare provider. If you subscribe to a Henry Meds weight management program, your medical practitioner will take time to evaluate your health status and discuss Semaglutide’s potential benefits and risks during your consultation.

Can You Take Metformin and Oral Semaglutide Together?

Yes, you may take oral Semaglutide and Metformin together if your healthcare provider recommends this combination. Combining Metformin and oral Semaglutide can be a powerful strategy in the treatment of Type 2 Diabetes Mellitus, especially when Metformin alone is not enough. The combination can also help manage body weight in adults with Type 2 Diabetes.¹²

Keep in mind, however, that the timing of intake of these medications matters if you’re taking the brand-name version, as opposed to the compounded sublingual form. Take Metformin at least 30 minutes after brand-name oral Semaglutide for optimal absorption and to avoid potential interactions.³¹ Avoid self-medication and always consult your doctor before deciding to combine medications. Your provider can help determine the best dose and schedule for you.

Combining oral Semaglutide and Metformin can be effective in managing blood sugar levels and body weight in suitable patients. However, individual needs and potential side effects have to be considered before starting with this treatment regimen. If you’re already enrolled in one of our treatment programs, you may ask your provider on the Henry Meds platform if this combination is appropriate for your health goals.

Disclaimers:

To help you trust the information we provide, every article written by Henry relies on peer-reviewed studies and medically reviewed facts. We ensure that data, ideas, and figures cited are reliable, current, and accurate. Our team of medical reviewers aims to help you cut through the noise with clear and authoritative primary and secondary sources.

Nothing in this article is intended to be prescriptive or medical advice. Talk to your doctor before starting a new diet and exercise plan. The information presented is about our medically supervised weight management programs and is not an advertisement for a specific drug.

Please note: Henry Meds does not offer Rybelsus®, which is only available from the Novo Nordisk company. Compounded Semaglutide is a patient-specific medication created in a state Board of Pharmacy or FDA-licensed compounding facility per a prescription from a licensed healthcare professional. Compounded drugs are required to exclusively use ingredients from FDA-licensed facilities, and test sterile compounds for potency, sterility, and purity. While compounded drugs are legal, they do not undergo pre-market approval from the FDA as they are not made in large batches for the public. Compounds are made based on specific orders from a medical professional. Because of that, the dose, route of administration, safety, and efficacy may differ from commercially available, brand-name drugs. Henry Meds exclusively works with licensed sterile compounding pharmacies in the United States.