Oral semaglutide vs injection: Which is better for you?

June 13, 2025

In the field of diabetes treatment and weight management, Semaglutide has become a shining star. As a glucagon-like peptide-1 (GLP-1) receptor agonist, it works by mimicking the GLP-1 hormone naturally produced by the human body, effectively controlling blood sugar and promoting weight loss. However, faced with two dosage forms, oral tablets and injections, many patients are often confused: which form is more suitable for my situation? This article will comprehensively compare the advantages and disadvantages of these two delivery methods to help you make a wise choice.

1. Understanding the two forms of semaglutide

Oral semaglutide (trade name Rybelsus) is the first and currently the only oral GLP-1 receptor agonist, approved by the FDA for the treatment of type 2 diabetes in 2019. Its innovation lies in breaking through the limitation that peptide drugs are usually destroyed by the gastrointestinal tract and achieving effective absorption through special absorption enhancers.

Injectable semaglutide is available in two forms: once-weekly Ozempic (for diabetes treatment) and Wegovy (a higher dose specifically for weight management). The injectable form is more directly absorbed in the body and has higher bioavailability.

2. Comparison of effectiveness: blood sugar control and weight loss effects

Clinical studies have shown that both formulations are excellent in reducing blood sugar , but there are some differences:

● HbA1c reduction : High-dose oral semaglutide (14 mg) can reduce HbA1c by about 1.2-1.4%, while the injection (1 mg) reduces it by an average of 1.5-1.8%. For patients with higher requirements for blood sugar control, the injection may have a slight advantage.

● Weight loss effect : Under standard dosage, oral dosage forms can reduce weight by an average of about 4-5kg, while injection dosage forms can reduce weight by 6-8kg. It is particularly noteworthy that Wegovy (semaglutide 2.4mg), which is specifically used for weight loss, can reduce weight by an average of about 15%, with a more significant effect.

● Speed of onset : Injectable dosage forms usually take effect faster because they enter the blood circulation directly; oral dosage forms require accumulation over several weeks to reach a stable blood drug concentration.

3. Convenience and User Experience

The obvious advantage of oral dosage forms is the mode of administration:

● No injection required, no needle fear

● Once a day, can be incorporated into morning routine

● Easy to carry, worry-free travel

● No injection site reactions (such as redness, swelling, and induration)

However, oral medications have strict requirements for taking : they must be taken on an empty stomach with a small amount of water, and no food or water can be consumed within 30 minutes after taking the medication. This poses a challenge to the daily routines of many people.

Although the injection form only needs to be taken once a week, it requires mastery of injection techniques and may cause temporary discomfort at the injection site. Its advantage is that it is not affected by mealtimes and the medication time is more flexible.

4. Comparison of side effects

The side effect profiles of the two dosage forms are similar , mainly including:

● Gastrointestinal reactions (nausea, vomiting, diarrhea, constipation)

Loss of appetite

Possible gallbladder problems

Rare risk of pancreatitis

Clinical data show:

The oral dosage form has a slightly lower incidence of gastrointestinal side effects, which may be related to its gradual absorption characteristics.

● Injectable dosage forms may have more obvious side effects at first due to higher peak blood concentrations, but they usually subside as the body adapts

V. Applicable population and special considerations

Oral medications may be more suitable for :

● Patients who refuse injections

● People who have a regular lifestyle and can strictly follow medication requirements

● Patients who only need moderate blood sugar control/weight loss

● People who travel frequently or have an active lifestyle

Injectables may be more ideal :

● Those who need stronger blood sugar control

● Seeking significant weight loss (especially if BMI ≥ 30 or ≥ 27 with obesity-related diseases)

● Those who have difficulty remembering to take their daily medications

● Sensitive gastrointestinal tract, more suitable for people with weekly side effects "shock" rather than daily mild discomfort

Note for special populations :

● Dose adjustment is required for patients with renal insufficiency (applicable to both formulations)

● Contraindicated in patients with a personal/family history of medullary thyroid cancer or MEN2 syndrome

● Safety during pregnancy has not been established and should be used with caution

Both oral and injectable semaglutide have their own strengths. There is no absolute "better", only "more suitable". You need to fully communicate with your doctor based on your personal situation to maximize the treatment effect while minimizing the interference in your life. No matter which form you choose, it can only achieve the best effect with lifestyle adjustments. Any drug treatment should be combined with diet, exercise and behavioral changes.