Medically reviewed by the HyaluFlow Health Editorial Team | Published: July 29, 2026 | Last Updated: July 29, 2026

Many people taking semaglutide worry that the medication stops working after several months. As hunger slowly returns, they often assume their body has become resistant to the drug.

New research suggests that is not what is happening. A 60-week randomized clinical trial from Penn Medicine found that people taking semaglutide continued eating significantly fewer calories than those receiving a placebo, even after the strong appetite-suppressing effects became less noticeable.[1][2]

The findings help explain why many people continue losing weight or maintain meaningful weight loss after a year of treatment.

Quick Answer

Yes. A new 60-week randomized controlled trial found that semaglutide users consistently consumed 24% to 30% fewer calories than placebo participants throughout the study. Although early hunger relief became less noticeable over time, the medication continued reducing actual food intake, supporting sustained long-term weight loss.[1]

Key Takeaways

  • Semaglutide remained effective after 60 weeks.
  • Participants consumed 24% to 30% fewer calories throughout the study.
  • Reduced calorie intake continued even when hunger partly returned.
  • Average weight loss reached 15.1% after 60 weeks.
  • Lifestyle counseling remained an important part of treatment.

Why This Matters

Semaglutide, sold under brand names such as Wegovy and Ozempic, has changed obesity treatment. However, one of the biggest concerns among patients is whether the medication eventually stops working.

Many users report that the intense reduction in appetite during the first few months becomes less obvious after four to six months. This often leads people to believe they have reached a plateau or developed resistance to the medication.

The new Penn Medicine study suggests that appetite and calorie intake are not always the same thing. Even when participants reported feeling hungrier than they did during the early months, they continued eating substantially fewer calories than those receiving placebo.[1][2]

This distinction is important because long-term weight loss depends primarily on maintaining a lower calorie intake rather than completely eliminating feelings of hunger.

Inside the Study

Researchers from Penn Medicine conducted a 60-week double-blind randomized controlled trial involving 120 adults living with overweight or obesity.

Participants were randomly assigned to receive either once-weekly semaglutide 2.4 mg or a placebo. Both groups also received lifestyle counseling focused on healthy eating and physical activity.[1]

Instead of relying only on questionnaires about hunger, researchers measured actual eating behavior.

At the beginning of the study and again at weeks 20, 40, and 60, participants completed a five-hour laboratory assessment. After eating a standardized breakfast, they were later offered lunch and instructed to eat until comfortably full. Researchers then measured exactly how many calories each participant consumed.[1]

By week 60, participants receiving semaglutide had lost an average of 15.1% of their starting body weight, compared with 3.4% in the placebo group.[1]

What Changed Over Time and What Didn't

During the first 20 weeks, participants taking semaglutide reported feeling less hungry, experiencing fewer food cravings, and thinking less about food than those taking placebo.

By weeks 40 and 60, many of those self-reported differences became smaller. Some participants noticed that hunger gradually returned, leading many to believe the medication was losing its effect.[1]

However, researchers found a very different pattern when they measured actual eating behavior.

Throughout the entire 60-week study, participants taking semaglutide consistently consumed 24% to 30% fewer calories than those receiving placebo. This reduction remained remarkably stable despite changes in perceived hunger.[1]

According to lead investigator Dr. Jena Tronieri, many patients become concerned when appetite begins returning after several months. The study suggests those feelings do not necessarily reflect how much food people actually eat.[2]

Why Semaglutide Keeps Working

Semaglutide belongs to a group of medicines called GLP-1 receptor agonists. These drugs mimic glucagon-like peptide-1, a natural hormone released by the intestine after eating.

GLP-1 helps regulate appetite through several different pathways. It slows stomach emptying, increases feelings of fullness after meals, and influences appetite centers within the brain.[3]

Researchers believe these biological effects continue even when the dramatic reduction in hunger becomes less noticeable.

In other words, patients may feel hungrier than they did during the first few months, yet still naturally eat smaller meals and consume fewer calories.

This difference between subjective hunger and objective calorie intake appears to be one of the key reasons semaglutide continues supporting long-term weight loss.[1][3]

What the Research Shows

The Penn Medicine trial is among the first studies to directly measure laboratory food intake for more than one year while participants remained on semaglutide.

The findings align with earlier STEP clinical trials, which consistently demonstrated average weight reductions of approximately 15% when semaglutide was combined with lifestyle intervention.[4]

The new study adds another important piece of evidence. It suggests that sustained weight loss is driven not only by early appetite suppression but also by continued reductions in calorie intake over time.

Researchers note that this may reassure patients who worry that their medication has stopped working simply because food thoughts or hunger become more noticeable several months into treatment.[1][2]

Potential Benefits Beyond Weight Loss

  • Supports long-term calorie reduction.
  • Helps maintain clinically meaningful weight loss.
  • Reduces reliance on willpower alone.
  • Works alongside healthy eating and physical activity.
  • May improve long-term adherence to weight management plans.

Who May Benefit from Semaglutide?

Semaglutide is not intended for cosmetic weight loss. It is approved for adults with obesity or for certain adults with overweight who also have at least one weight-related medical condition, such as type 2 diabetes, high blood pressure, or high cholesterol.

Healthcare providers consider factors such as body mass index (BMI), medical history, and overall health before prescribing the medication.[5]

Semaglutide works best when combined with healthy eating, regular physical activity, adequate sleep, and long-term lifestyle changes.

Common Side Effects

Like all medications, semaglutide can cause side effects. Most are mild to moderate and improve as the body adjusts.

  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Abdominal pain
  • Reduced appetite
  • Fatigue

Doctors usually increase the dose gradually to reduce digestive side effects.[5]

Possible Serious Risks

Serious side effects are uncommon but can occur. Seek immediate medical attention if symptoms develop.

  • Severe abdominal pain that may indicate pancreatitis.
  • Gallbladder problems, including gallstones.
  • Kidney injury related to severe dehydration.
  • Serious allergic reactions.
  • Vision changes, especially in people with diabetes.

Some studies have also explored a possible association between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION). More research is needed to better understand this potential risk.[6]

Who Should Be Careful?

Semaglutide is not appropriate for everyone.

Talk with your healthcare provider before starting treatment if you:

  • Have a personal or family history of medullary thyroid carcinoma.
  • Have Multiple Endocrine Neoplasia syndrome type 2 (MEN2).
  • Have a history of pancreatitis.
  • Have severe stomach emptying problems, including gastroparesis.
  • Are pregnant, planning pregnancy, or breastfeeding.
  • Have severe kidney disease or significant digestive disorders.

Your healthcare provider can determine whether semaglutide is appropriate based on your medical history and current medications.[5]

Study Limitations

Although the findings are encouraging, the study has several limitations.

Only 120 adults participated in the trial, so larger studies are needed to confirm the results across more diverse populations. The study also lasted 60 weeks, which provides valuable long-term data but does not show whether the same effects continue after several years of treatment.[1]

Another important point is that every participant received structured nutrition and physical activity counseling. The results therefore reflect the combination of medication and lifestyle support rather than semaglutide alone.

Researchers also measured food intake during controlled laboratory meals. While this provides accurate data, eating habits in everyday life may differ from those observed in a research setting.

What This Means for Patients

The study offers reassuring news for people taking semaglutide.

If your appetite starts returning after several months, it does not automatically mean the medication has stopped working. Many participants continued eating significantly fewer calories despite reporting more hunger than they experienced early in treatment.[1][2]

Instead of judging progress only by how hungry you feel, healthcare professionals recommend monitoring long-term trends such as body weight, waist circumference, healthy eating habits, physical activity, and overall health improvements.

Stopping treatment without discussing it with your healthcare provider could increase the risk of weight regain, especially if healthy lifestyle habits have not yet become established.[4][5]

Bottom Line

A new 60-week randomized clinical trial provides strong evidence that semaglutide continues working well beyond the first year of treatment.

Although the dramatic reduction in hunger seen during the first few months may become less noticeable, participants consistently consumed 24% to 30% fewer calories than those receiving placebo throughout the study. This sustained reduction in calorie intake appears to be one of the main reasons semaglutide continues supporting long-term weight loss.[1]

Like any prescription medication, semaglutide works best when combined with healthy eating, regular physical activity, and ongoing medical supervision. For eligible patients, it remains one of the most effective evidence-based treatments currently available for long-term weight management.[4][5]

References

  • [1] Tronieri JS, et al. Short- and Long-term Effects of Semaglutide 2.4 mg on Energy Intake, Appetite, and Food Reward: A 60-week Double-blind Randomized Controlled Trial. American Journal of Clinical Nutrition. 2026.
  • [2] Penn Medicine News. Semaglutide Sustains Lower Calorie Intake for More Than a Year. University of Pennsylvania. 2026.
  • [3] Cleveland Clinic. GLP-1 Agonists: What They Are, How They Work, Benefits and Risks.
  • [4] Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1 Trial). New England Journal of Medicine.
  • [5] Mayo Clinic. Semaglutide (Subcutaneous Route): Uses, Side Effects and Precautions.
  • [6] Hathaway JT, et al. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmology. 2024.
  • [7] Centers for Disease Control and Prevention (CDC). Adult Obesity Facts.