GLP-1 (glucagon-like peptide-1) receptor agonists such as Ozempic, Wegovy, and Rybelsus — all of which contain the active ingredient semaglutide — can cause a profound, lingering tiredness. Understanding the relationship between GLP-1s and energy levels is the first step toward reclaiming your vitality while achieving your health goals.

Yes, fatigue (sometimes referred to as asthenia or malaise in medical literature) is a recognized side effect of semaglutide.

The frequency of this side effect varies depending on the specific medication and the condition being treated. For example:

  • Wegovy: In clinical trials for ongoing weight management, approximately 11% of adult patients reported fatigue, compared to 5% in the placebo group.
  • Ozempic: While less common in trials focusing on type 2 diabetes, fatigue is still noted as a potential side effect, particularly when the dose is increased.
  • Rybelsus: The oral version of semaglutide also lists fatigue as a potential adverse reaction in its clinical documentation.

There are several reasons why you’re so tired after starting these medications.

First, semaglutide works by slowing gastric (stomach) emptying and signaling the brain to feel full. This often leads to a significant reduction in caloric intake. If your body isn’t receiving enough fuel in the form of calories, your energy levels will naturally dip.

Secondly, these medications influence metabolic processes. As your body adjusts to new blood sugar patterns and shifts from using readily available glucose to burning stored fat, you may experience a metabolic lag.

Finally, gastrointestinal side effects such as nausea, vomiting, and diarrhea can lead to dehydration and poor sleep, both of which contribute to exhaustion.

For most people, fatigue associated with semaglutide is temporary. It most commonly occurs during the titration phase (the period during which your doctor gradually increases your dose to reach the maintenance level).

Prescribing information for Wegovy and Ozempic emphasizes a gradual dose increase over the course of several months to improve how well your body tolerates the medication. Many patients report that the brain fog or lethargy begins to lift once they have been on a stable maintenance dose for a few weeks.

Typically, the most intense fatigue lasts for the first 4 to 8 weeks of treatment. However, if the fatigue is mainly caused by an extreme calorie deficit or nutritional gaps, it may continue until you adjust your eating habits to support your energy needs.

If you’re struggling with fatigue, here are some evidence-based strategies to boost your energy levels:

  1. Prioritize protein: When your appetite is suppressed, every bite counts. Focus on high-quality lean proteins (like chicken, fish, tofu, or Greek yogurt). Protein helps preserve muscle mass during weight loss, which is essential for maintaining a healthy metabolism and preventing the sluggish feeling associated with muscle wasting.
  2. Hydrate with electrolytes: GLP-1 medications can increase the risk of dehydration, especially if you’re experiencing nausea. Drinking plenty of water is essential, but adding electrolytes (sodium, potassium, and magnesium) can help maintain nerve and muscle function, which often helps clear the fog of fatigue.
  3. Eat small, frequent meals: Even if you don’t feel hungry, your body needs a steady supply of energy. Instead of three large meals, try four or five small, nutrient-dense snacks throughout the day to keep your blood sugar stable.
  4. Monitor your caloric intake: While weight loss is often the goal, losing weight too rapidly or eating fewer than 1,200 calories (for women) or 1,500 calories (for men) can send your body into a state of exhaustion. Be sure to monitor your caloric intake (in writing or using a tracking app) for a few days to ensure you aren’t under-eating to a dangerous degree.
  5. Check your vitamin levels: Your body needs vitamin B12 to create energy. However, because medications like Wegovy and Ozempic change how you digest food, you might not be absorbing enough of it. Not having enough B12 in your system can make you feel even more exhausted. Talk with your doctor if you have questions about taking vitamin B12 supplements during your GLP-1 treatment.

While mild to moderate fatigue is common, it should not be debilitating. You should consult a healthcare professional if:

  • The fatigue interferes with daily life: If you’re unable to work, drive, or complete basic tasks due to exhaustion.
  • You experience signs of severe dehydration: This includes extreme thirst, dark-colored urine, or dizziness when standing up.
  • You have symptoms of hypoglycemia: If you’re taking Ozempic or Rybelsus alongside other diabetes medications like insulin or sulfonylureas, your fatigue could be a sign of dangerously low blood sugar. Symptoms include shakiness, sweating, and confusion.
  • The fatigue is accompanied by severe abdominal pain: This could indicate more serious complications like pancreatitis or gallbladder problems, which are rare but serious risks associated with GLP-1 medications.

Your doctor may recommend adjusting your dose, checking your iron or B12 levels, or switching to a different medication.

Medical Perspective

If you don’t follow the recommended diet while on a GLP-1 drug, you may not get enough nutrients. This can cause problems like fatigue, hair loss, or muscle weakness. Poor diet choices can also make side effects like nausea or constipation worse. And for people with diabetes, it may increase the risk of low blood sugar.

— Andrew Perugini, PharmD

For more information about potential side effects of these medications, check out this guide to GLP-1 side effects.

Quotes represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.

Fatigue is a common and recognized side effect of semaglutide medications. It’s often the result of reduced calorie intake, changes in your metabolism, or dehydration.

While this exhaustion is usually temporary and most intense during the first 4 to 8 weeks of treatment, it can be managed by prioritizing high-quality protein, maintaining electrolyte balance, and ensuring you do not drop below a healthy calorie limit.

If your fatigue becomes debilitating or is accompanied by severe symptoms like confusion or intense abdominal pain, you should consult a healthcare professional to discuss dose adjustments or potential nutritional deficiencies.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.