Dr Nick Fuller
Leading Obesity Expert at the University of Sydney and founder of Interval Weight Loss.
Semaglutide is a GLP-1 receptor agonist originally developed for type 2 diabetes, now also widely prescribed for weight loss. Clinical trials have shown it can be highly effective for reducing body weight, but like any medication, it comes with side effects. One that many people notice is fatigue.
The STEP 1 trial, which tested once-weekly semaglutide for weight management, reported fatigue among participants, though usually at mild or moderate levels. The U.S. FDA prescribing information for Wegovy also lists fatigue among the more common adverse reactions. While the tiredness is not universal, it’s common enough that many patients wonder whether semaglutide is directly responsible or if other factors, like reduced food intake and the body’s survival response, play a role.
Research also shows that GLP-1 medications significantly reduce caloric intake, sometimes by as much as 16–39% compared to placebo. That change alone can leave people feeling drained, particularly in the early stages of treatment when the body is adapting. Add in the effects of nausea, dehydration, or disrupted sleep from other side effects, and it’s easy to see how fatigue can become part of the picture.
In this article, we’ll look at what the evidence says about semaglutide and tiredness, unpack the possible causes, and explore what it might mean for people aiming for long-term weight loss.
Semaglutide offers more than just a boost to weight loss. It supports long-term health in several important ways, making it a treatment option worth considering if prescribed by your doctor.
Supports long-term weight loss
In the STEP 1 trial, participants taking semaglutide lost an average of almost 15% of their body weight compared to about 2% in the placebo group. What makes this significant is not just the initial loss, but the ability to sustain it over time, something most traditional diets fail to achieve.
Improves blood sugar control
Semaglutide mimics the GLP-1 hormone, which helps regulate glucose by stimulating insulin release and reducing excess sugar production in the liver. This dual action improves insulin sensitivity and leads to more stable blood sugar levels.
Helps manage type 2 diabetes
For people with type 2 diabetes, semaglutide is a proven therapy that reduces HbA1c levels and improves overall metabolic health. Beyond lowering blood sugar, it also helps reduce diabetes-related risks, offering a more comprehensive management approach.
Reduces appetite and cravings
One of the main ways semaglutide aids weight management is by reducing hunger and food cravings. Research shows patients on GLP-1 medications eat significantly fewer calories, up to 39% less than those not on the medication. This effect helps people stick to healthier eating patterns without feeling constantly deprived.
Lowers cardiovascular risk
Beyond weight and blood sugar, semaglutide has been shown to lower the risk of major cardiovascular events, including heart attack and stroke. For patients with both obesity and type 2 diabetes, this makes the medication especially valuable in protecting long-term heart health.
Not everyone who takes semaglutide feels fatigued, but for those who do, the tiredness can usually be explained by a few key factors.
One common side effect of semaglutide is nausea, which may reduce fluid intake and increase the risk of dehydration. Even mild dehydration can cause fatigue, headaches, and poor concentration. Staying adequately hydrated is essential while on medication.
Semaglutide helps lower blood sugar by improving insulin release and reducing glucose production. For some people, this adjustment can temporarily cause dips in blood sugar, which may leave them feeling weak or tired until their body adapts.
By mimicking GLP-1, semaglutide alters several hormonal pathways related to appetite, digestion, and glucose metabolism. These shifts can affect how your body regulates energy and may contribute to feelings of fatigue, especially in the first weeks of treatment.
The body is wired to resist weight loss. When semaglutide reduces calorie intake, your metabolism may slow down to conserve energy, a survival mechanism that makes you feel more tired. This phenomenon, often called metabolic adaptation, has been observed in studies on dieting and weight loss.
Some people on semaglutide report sleep disturbances, either from gastrointestinal side effects or changes in daily energy levels. Poor sleep itself is a major contributor to daytime fatigue and can worsen the sense of tiredness linked to the medication.
Semaglutide lowers appetite, which means many patients eat significantly fewer calories. While this supports weight loss, it can also reduce available energy, particularly if the body is not yet fully adjusted to the lower intake.
Fatigue can sometimes be the result of side effects beyond semaglutide’s impact on appetite and metabolism. Here are a few that may contribute to feeling low on energy.
Nausea, constipation, diarrhoea, and bloating are among the most common side effects of semaglutide. These issues can disrupt eating and hydration, which in turn may leave you feeling weak or tired.
Some patients experience headaches or light-headedness while adjusting to semaglutide. These symptoms can be draining, especially when combined with reduced calorie intake.
Sleep issues are sometimes reported, either because of digestive discomfort or changes in overall energy levels. Poor sleep itself is one of the most direct causes of daytime fatigue.
Mild redness, swelling, or discomfort at the injection site is not uncommon. While these don’t directly cause fatigue, they can add to overall discomfort, indirectly affecting energy levels.
Though rare, semaglutide carries a boxed warning for potential thyroid C-cell tumours based on rodent studies. While extremely uncommon in humans, awareness of this risk is important, particularly if thyroid problems contribute to tiredness.
Fatigue from semaglutide doesn’t usually last forever. For most people, tiredness is most noticeable in the first weeks of treatment as the body adjusts to lower calorie intake, changes in blood sugar, and other side effects.
In many cases, people notice fatigue easing after the first month, especially once they stabilise their eating patterns and hydration. However, for some, low energy can linger if side effects like nausea, diarrhoea, or poor sleep continue. Adjustments to dose, timing, or supportive strategies (such as better hydration and balanced nutrition) may help reduce symptoms.
It’s important to remember that the experience is individual. Some patients never feel unusually tired, while others may find fatigue significant enough to discuss with their doctor about whether dose adjustments or alternative options are appropriate.
Fatigue from semaglutide is usually temporary, and there are practical steps you can take to support your energy and help your body adjust:
Eat balanced, frequent meals: Smaller meals rich in lean protein, whole grains, and vegetables help stabilise blood sugar and may reduce dips in energy. Research shows that consistent intake of complex carbohydrates and protein supports steady energy release.
Stay well hydrated: Dehydration is linked to increased fatigue. If nausea makes it difficult to drink plain water, try sipping slowly or adding lemon, cucumber, or herbal teas to make fluids more palatable.
Improve sleep quality: Good sleep hygiene, such as going to bed at consistent times, reducing screen use before sleep, and creating a cool, dark environment, has been shown to improve daytime energy and mood.
Add gentle activity: Light exercise like walking or stretching can boost circulation and reduce feelings of sluggishness. Even short bouts of activity have been shown to increase energy levels and reduce fatigue.
Manage stress: Relaxation techniques, such as mindfulness, journalling, or breathing exercises, can help reduce stress levels, which in turn may alleviate feelings of tiredness.
Consult your healthcare provider: If fatigue persists or worsens, it’s important to rule out other causes. Your doctor may adjust your dosage or suggest additional strategies tailored to your health needs.
Fatigue from semaglutide is often temporary, but there are situations where it’s important to check in with your healthcare provider. If your tiredness is worsening or lasting beyond the initial adjustment period, it could signal an underlying issue that needs evaluation.
Persistent dehydration symptoms, such as dizziness, dry mouth, or dark urine, also warrant medical attention, as they can affect overall health and energy levels. Similarly, severe gastrointestinal distress, including intense nausea, vomiting, or diarrhoea, or episodes of low blood sugar, may require dose adjustments or additional interventions to keep you safe.
Finally, while rare, suspected thyroid concerns or significant reactions at injection sites should always be reported to a healthcare professional. These issues, though uncommon, are important to monitor to ensure that semaglutide remains a safe and effective part of your treatment plan.
Fatigue is a common, but usually temporary, side effect of semaglutide. It can occur due to factors like reduced calorie intake, dehydration, changes in blood sugar, hormonal shifts, metabolic adaptation, and sleep disturbances. Not everyone experiences tiredness, and how severe it is varies from person to person.
Practical strategies can help you maintain energy while your body adjusts. Eating balanced, frequent meals, staying hydrated, maintaining good sleep routines, adding light activity, and managing stress can all make a noticeable difference.
It’s also important to know when to check in with your doctor. Persistent fatigue, severe gastrointestinal issues, low blood sugar episodes, or rare concerns like thyroid issues or injection-site reactions should be evaluated to ensure your treatment remains safe and effective.
With careful management and medical guidance, semaglutide can continue to support weight management and overall health while minimising tiredness and other side effects.
Looking for ways to manage fatigue and maintain energy while on semaglutide? Check out What to Eat While Taking Weight Loss Injections for science-backed tips on nutrition that can help support your energy, preserve muscle, and reduce side effects.
Dr Nick Fuller is the founder of Interval Weight Loss and is a leading obesity expert at the University of Sydney with a Ph.D. in Obesity Treatment. Dr Fuller is also the author of three best-selling books and his work been published in top ranked journals in the medical field, including JAMA, Lancet and American Journal of Clinical Nutrition.