Is semaglutide good for long-term weight loss? A Comprehensive Analysis

October 9, 2025 •

4 min read

Studies show that once-weekly semaglutide can lead to a mean weight loss of 10% to 15% of body weight [1.3.3, 1.2.6]. But a key question remains for many: is semaglutide good for long-term weight loss and maintenance? The answer requires a deeper look into its mechanism, clinical trial data, and what happens when the medication is discontinued.

Quick Summary

Semaglutide demonstrates significant and sustained weight loss for up to four years with continued use [1.2.1]. However, treatment is required to maintain these results, as discontinuing the drug often leads to weight regain [1.4.3].

Key Points

Sustained Efficacy: Clinical trials show semaglutide can sustain significant weight loss (around 10% of body weight) for up to four years with continuous use [1.2.1, 1.2.4].
Chronic Treatment Needed: Obesity is a chronic disease; continuous treatment with semaglutide is necessary to maintain weight loss and health benefits [1.4.3].
Weight Regain is Common: Discontinuing semaglutide typically leads to regaining a substantial portion (around two-thirds) of the lost weight within a year [1.4.3].
Cardiovascular Benefits: Beyond weight loss, semaglutide significantly reduces the risk of major cardiovascular events in patients with obesity and established heart disease [1.8.2].
Mechanism of Action: It works by mimicking the GLP-1 hormone to suppress appetite, slow stomach emptying, and regulate blood sugar [1.7.2, 1.7.5].
Common Side Effects: The most frequent side effects are gastrointestinal (nausea, diarrhea) and are usually transient and mild-to-moderate [1.3.3].
Not a 'Cure': Semaglutide is a long-term management tool, not a one-time fix. Its effectiveness depends on consistent, ongoing administration [1.3.2].

Understanding Semaglutide and Its Mechanism of Action

Semaglutide is a medication classified as a glucagon-like peptide-1 (GLP-1) receptor agonist [1.7.2]. It was initially developed to treat Type 2 diabetes but has proven highly effective for chronic weight management [1.2.6]. It works by mimicking the natural GLP-1 hormone in the body, which has several effects that contribute to weight loss [1.7.5]:

Appetite Suppression: Semaglutide acts on the brain's appetite centers, particularly the hypothalamus, to increase feelings of fullness and reduce hunger and food cravings [1.7.1, 1.7.3]. This leads to a natural reduction in calorie intake.
Slowed Gastric Emptying: The medication slows down how quickly the stomach empties its contents. This prolongs the feeling of satiety after a meal, helping to curb overeating [1.7.2].
Blood Sugar Regulation: By enhancing the body's insulin response to high blood sugar, semaglutide helps stabilize glucose levels, which can indirectly influence hunger and energy [1.7.2].

These combined actions help individuals consume fewer calories and make adhering to a healthier lifestyle more manageable [1.7.5].

Long-Term Efficacy: What the Clinical Trials Show

The most extensive evidence for semaglutide's long-term effectiveness comes from the Semaglutide Treatment Effect in People with Obesity (STEP) and SELECT clinical trials. A key analysis from the SELECT trial, which followed over 17,000 adults, found that patients taking semaglutide sustained clinically significant weight loss for up to four years [1.2.1, 1.2.4].

Key findings from long-term studies:

Sustained Weight Loss: At 208 weeks (4 years), patients on semaglutide showed an average weight reduction of 10.2%, compared to just 1.5% for those on a placebo [1.2.1]. They also saw a significant reduction in waist circumference [1.2.4].
Clinically Meaningful Results: After two years, over half of the adults taking semaglutide moved down at least one BMI category, and 12% achieved a healthy BMI (under 25), compared to just 1% in the placebo group [1.3.4].
Cardiovascular Benefits: The SELECT trial also demonstrated that semaglutide reduces the risk of major adverse cardiovascular events (like heart attack or stroke) by 20% in people with pre-existing cardiovascular disease and obesity, irrespective of the amount of weight lost [1.8.2]. This benefit was observed to start as early as three months into treatment [1.8.4].

The Critical Role of Continuous Treatment

While effective, the benefits of semaglutide are tied to its continued use. Obesity is considered a chronic disease, and like other chronic conditions, it requires long-term treatment [1.3.2, 1.4.3].

Studies on what happens after discontinuing semaglutide consistently show a pattern of weight regain. An extension of the STEP 1 trial found that one year after stopping the medication, participants regained approximately two-thirds of the weight they had lost [1.4.3]. Similarly, cardiometabolic improvements like lower blood pressure and better lipid profiles also reverted toward baseline levels after withdrawal [1.4.3].

However, some research suggests that not everyone regains all the weight. One study found that about 56% of patients maintained their weight loss or continued to lose weight a year after stopping the medication, though a smaller percentage (around 18%) regained all they had lost or more [1.4.2, 1.4.4]. This highlights the variability in individual responses and the importance of ongoing lifestyle interventions [1.4.6].

Comparison with Other Weight Loss Options

When considering long-term options, it's helpful to compare semaglutide to other treatments.


Treatment Approach	Average Long-Term Weight Loss	Key Considerations
Semaglutide (2.4mg)	10-15% sustained with continued use [1.3.3, 1.2.2]	Requires weekly injection; potential for GI side effects; weight regain upon discontinuation [1.4.3].
Tirzepatide	18-21% [1.6.1, 1.6.4]	A dual GLP-1/GIP agonist, may be more effective for weight loss than semaglutide alone [1.6.3]. Also requires continuous use.
Lifestyle Intervention Alone	2-5% [1.3.3, 1.2.5]	Challenging to sustain; body may adapt to resist weight loss [1.4.5].
Bariatric Surgery	20-30%	Invasive procedure; requires significant lifestyle changes; potential for complications and weight regain over time. Semaglutide may be used to treat weight regain after surgery [1.2.5].

Potential Side Effects and Safety

The most common side effects of semaglutide are gastrointestinal and include nausea, diarrhea, vomiting, constipation, and abdominal pain [1.5.1, 1.5.3]. These are typically mild to moderate, often occur during the initial dose-escalation period, and tend to subside over time [1.3.3]. Starting with a low dose and increasing it gradually can help manage these effects [1.5.1].

More serious, though less common, side effects can include:

Pancreatitis (inflammation of the pancreas) [1.5.5]
Gallbladder problems (like gallstones) [1.2.5]
Changes in vision [1.5.2]
Kidney problems [1.5.5]
Risk of thyroid C-cell tumors (based on animal studies, the risk in humans is not fully known) [1.5.2]. It is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 [1.5.2].

Conclusion

So, is semaglutide good for long-term weight loss? The evidence strongly indicates that it is highly effective for achieving and, crucially, sustaining significant weight loss and cardiovascular benefits for as long as it is taken [1.2.1, 1.2.4]. The key is to view obesity as a chronic disease that requires ongoing management. Semaglutide is not a short-term cure but a long-term treatment. Discontinuation will likely lead to weight regain, underscoring the need for continuous therapy combined with a healthy lifestyle to maintain its profound benefits.

For an authoritative source on the primary clinical trial, visit: https://www.nejm.org/doi/full/10.1056/NEJMoa2307563 [1.8.2].

Frequently Asked Questions

Long-term studies, such as the SELECT trial, show that patients on semaglutide can sustain an average weight loss of about 10.2% of their initial body weight over four years with continuous treatment [1.2.1].

Current evidence suggests that ongoing treatment is required to maintain weight loss. Studies show that when semaglutide is discontinued, patients tend to regain a significant portion of the weight they lost, as the medication's effects on appetite and satiety wear off [1.4.3].

The most common side effects are gastrointestinal, including nausea, diarrhea, vomiting, and constipation. These effects are typically mild-to-moderate and often decrease over time as the body adjusts to the medication [1.5.1, 1.3.3].

Yes. In patients with overweight or obesity and pre-existing cardiovascular disease, semaglutide has been shown to reduce the risk of major adverse cardiovascular events (like heart attack and stroke) by 20% [1.8.2]. It also improves factors like blood pressure and cholesterol [1.3.5].

Upon stopping semaglutide, the medication's effects dissipate. This leads to a return of appetite and hunger, and most people regain a significant amount of the weight they lost. One study found that a year after withdrawal, participants regained about two-thirds of their prior weight loss [1.4.3, 1.4.5].

Studies of up to four years have shown semaglutide to be generally safe, with a lower rate of serious adverse events compared to placebo [1.2.1]. However, it does carry risks, including potential gastrointestinal issues, pancreatitis, and a warning for thyroid tumors. It should only be used under medical supervision [1.5.2, 1.5.4].

Tirzepatide, a dual GLP-1/GIP agonist, has shown slightly greater weight loss results in some studies, with patients potentially losing up to 20% of their body weight [1.6.2, 1.6.4]. Both medications require continuous use for sustained results and share similar side effect profiles, though some users report fewer severe side effects with tirzepatide [1.6.1].