The Long-Term Weight Loss Effects of Semaglutide in People with Obesity but No Diabetes

 

In recent years, semaglutide has emerged as one of the most promising medications in the fight against obesity. Originally developed to treat type 2 diabetes, semaglutide has since gained attention—and regulatory approval—for its potent weight loss effects, even in individuals without diabetes. But how effective is semaglutide in the long run? And is it a sustainable option for weight management in people with obesity but no diabetes?

Let’s dive into what the science says and explore how semaglutide could reshape the future of weight loss treatment.

What is Semaglutide?

Semaglutide is a medication that mimics a naturally occurring hormone in the body called glucagon-like peptide-1 (GLP-1). This hormone plays a crucial role in regulating appetite, food intake, and blood sugar levels. By activating GLP-1 receptors, semaglutide helps people feel fuller sooner and reduces hunger between meals.

Initially prescribed for managing type 2 diabetes (marketed as Ozempic), semaglutide was later formulated at a higher dose (2.4 mg weekly) and approved by the FDA in 2021 for chronic weight management under the brand name Wegovy®.

Long-Term Weight Loss: What the Research Shows

One of the most comprehensive studies examining semaglutide's effects on people with obesity but without diabetes is the STEP 1 trial, published in the New England Journal of Medicine in 2021. The trial enrolled over 1,900 adults with obesity or overweight (with at least one weight-related condition) but no history of diabetes. Participants received either weekly semaglutide injections or a placebo, along with lifestyle counseling.

Key results after 68 weeks (around 16 months):

• Participants taking semaglutide lost an average of 14.9% of their body weight.

• In contrast, those in the placebo group lost just 2.4%.

• Nearly 70% of semaglutide users lost at least 10% of their body weight.

• About 32% lost 20% or more of their weight—results comparable to those seen with bariatric surgery.

These results marked a paradigm shift in how the medical community views pharmacologic obesity treatment. But they also raised a crucial question: What happens after 68 weeks?

Weight Maintenance and Continued Use

Obesity is a chronic, relapsing condition, much like hypertension or high cholesterol. When people stop taking medication, the effects often wane. Unfortunately, semaglutide is no exception.

In a follow-up study called STEP 4, researchers found that people who stopped taking semaglutide after the initial 20-week dose escalation period regained a significant portion of their lost weight over the following 48 weeks. Conversely, those who continued taking semaglutide maintained or even slightly improved their weight loss.

This underscores a key point: Long-term weight loss with semaglutide is generally dependent on continued use. Stopping the medication often results in weight regain, likely due to the return of normal appetite and eating behaviors.

Safety and Side Effects Over Time

Like all medications, semaglutide comes with potential side effects. The most commonly reported ones are gastrointestinal—nausea, vomiting, diarrhea, constipation, and abdominal discomfort. These tend to be more intense during the dose-escalation period and often subside with time.

Long-term safety data remain generally reassuring. Studies up to two years in length show a consistent safety profile with no major red flags. However, people with a history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 should not use semaglutide, as it may increase the risk of certain thyroid tumors.

Is Semaglutide a Magic Bullet for Obesity?

The short answer: no—but it’s a powerful tool.

Semaglutide doesn't cure obesity, but it can significantly improve weight-related health risks and quality of life. Its benefits go beyond just the number on the scale. Clinical trials have documented improvements in:

• Blood pressure

• Cholesterol levels

• Sleep apnea symptoms

• Physical function

• Mental health and self-esteem

For many, semaglutide may be the first time a medical treatment has delivered sustainable and significant weight loss without surgery.

Barriers and Considerations

Despite its effectiveness, semaglutide isn't accessible to everyone. The cost is a major barrier, especially for those without insurance coverage. Wegovy can cost over $1,000 per month in the U.S., placing it out of reach for many who would benefit.

In addition, some individuals may not tolerate the side effects or may have medical conditions that contraindicate use. Semaglutide is most effective when paired with lifestyle changes, including healthy eating, physical activity, and behavioral support—factors that require ongoing commitment.

Conclusion: A New Era in Obesity Treatment

The long-term weight loss effects of semaglutide in people with obesity but no diabetes are impressive, clinically significant, and potentially life-changing. For the first time, a medication has been shown to produce double-digit weight loss with an acceptable safety profile and sustained effects—as long as it is taken consistently.

However, semaglutide is not a one-size-fits-all solution. It should be considered as part of a comprehensive, personalized weight management strategy developed with a healthcare provider. As research continues, and as newer medications and combination therapies enter the market, the landscape of obesity treatment is undergoing a major transformation.