Does semaglutide make you tired?

Unless you have been living under a rock, you have probably heard about the revolutionary weight loss drug semaglutide, also known as Wegovy. However, as with any medication, users may experience some side effects, and the one we will be discussing today is fatigue or tiredness. This blog will explore this adverse effect and answer the question: Does semaglutide make you tired? So, grab your coffee (especially if you just had your dose of semaglutide), sit back, and read about how semaglutide causes tiredness and fatigue.

We have prepared these handy summary bullet points for those who want the facts….now!

Summary

• Semaglutide is approved for people with Type II diabetes and for those who are obese or overweight with an additional health condition.
• This medication aids weight loss by reducing appetite, which lowers caloric intake, which can naturally lead to tiredness.
• Tiredness may also result from semaglutide side effects, including nausea, vomiting, and diarrhoea.
• Fatigue and tiredness may be due to a lack of essential nutrients and protein.

In this article, we’ll dive into why semaglutide might cause tiredness, what factors contribute to this side effect, and ways you can manage fatigue while on this medication. If you’re considering semaglutide for weight loss, understanding the potential side effects can help you make an informed choice for your health journey. But before we start investigating why Wegovy can make you tired, we will first go over some basics about weight loss and semaglutide. If you want to skip sections you are already familiar with, you can use the handy navigational table to read the sections that interest you.

What is obesity?

Obesity isn’t just about extra weight; it involves changes in how much and where fat is stored [1] and how it functions in the body. These changes often result from genetic, metabolic, and hormonal factors, as well as lifestyle and environmental influences that affect how our body manages energy and stores fat.

In addition to these influences, individual factors like personal genetics (epigenetics) and gut health (the microbiome) can also play a role. These factors affect our body’s balance between energy intake and activity levels, which can lead to increased fat storage.

When energy intake, food, is greater than expenditure in the form of physical activity, then this excess energy is stored as fat [2]. In fact, our bodies view fat as energy. Like a savings account is kept for a rainy day; likewise, fat stores are kept to allow us to survive in times of famine. So, even though we would like to shed our fat, our bodies, on the other hand, are loathe to see it go and try to hold on to it. Being overweight or obese is testament to the fact that the body has won this round of the weight loss war, but little did it expect that you can now recruit allies in the form of GLP-1 agonists like semaglutide.

Definition of obesity

Why is it important to have a working definition of obesity? Well, it is used to determine if you can get semaglutide or Wegovy on a prescription to help with your weight loss, and it’s all to do with your BMI or Body Mass Index. Before we tell you about the BMI cut-off points for semaglutide, let’s have a closer look at what BMI measures.

Body Mass Index (BMI) is a measure used to identify body weight levels. It’s calculated by dividing a person’s weight in kilograms by the square of their height in meters. For adults, a BMI between 25 and 29.9 kg/m² is classified as overweight, while a BMI of 30 kg/m² or more is classified as obese [3].

To be eligible for semaglutide, you must either:

• Have a BMI greater than 30 kg/m², or
• Have a BMI greater than BMI of 27 kg/m2 or more in the presence of at least one weight-related co-morbidity, such as hypertension, dyslipidaemia, or type 2 diabetes.

I bet you’re curious to check your BMI now! Well, you can do that by using the NHS BMI calculator.

Obesity management

Previously, lifestyle management was the treatment of choice to combat obesity, but the results were modest, with most of the weight loss being regained [4]. Remember how I said that the body hates to see fat leave? When you lose the pounds, the body does everything to get it back in kilos. As anyone who has tried to lose weight will know, it’s incredibly hard to keep any weight off once it has been lost. 

When we were left with only our willpower to rely on to lose weight, our bodies usually won the battle. Losing weight was like Sisyphus pushing the boulder up the hill, only to see it roll down again when he reached the top. We lost weight and nearly reached our goals, only to fail, but now reinforcements have arrived from big pharma, and the tide in the war against weight loss has turned.

The pharmaceutical industry developed several drugs to help treat obesity. These include the fat absorber Orlistat, phentermine-topiramate, and naltrexone-bupropion, which typically show moderate results (~3%-9% mean weight loss over that achieved with lifestyle intervention alone) [5].

GLP-1 agonists…the game changers

GLP-1 agonists are drugs initially developed to help manage type 2 diabetes and are now also used as effective treatments for obesity. These medications mimic a natural hormone in the body that helps regulate blood sugar levels and appetite.

The first drug in the GLP-1 agonist class, exenatide, was inspired by a compound found in the saliva of the Gila monster, a lizard from the southwestern U.S. known for its incredibly sparse diet, consuming only around five to ten meals a year. Given its ability to survive on such limited intake, it’s fitting that a groundbreaking weight-loss drug would emerge from the study of this animal. Like the Gila monster, which optimises energy use over long intervals, GLP-1 agonists help humans manage appetite and energy balance. This connection highlights how the lizard’s natural biology contributed to developing drugs that influence human hunger, satiety, and even blood sugar regulation, leading to breakthroughs in diabetes and obesity treatments.

By activating the GLP-1 pathway, these drugs slow gastric emptying, promote fullness, and reduce overall caloric intake [6], aligning well with the Gila monster’s efficient metabolism.

Liraglutide or Saxenda, the first GLP-1 agonist licensed for weight loss

The first GLP-1 agonist to be licensed for weight loss was liraglutide or Saxenda, given as a 3.0 mg daily injection. Clinical trials lasting 20-56 weeks demonstrated that participants on liraglutide lost an additional 4-6% of body weight compared to those on lifestyle changes alone.

In these studies, 46%- 76% of participants achieved a weight reduction of at least 5%, and 23%- 37% lost 10% or more of their initial body weight [7], [8].

So, the era of the GLP-1 agonist began. However, one drawback to liraglutide or Saxenda was that it had to be administered by subcutaneous injection daily. For many, it was hard to inject oneself, let alone have to do it daily. This naturally affected compliance, but it all changed with the arrival of semaglutide.

What is Semaglutide?

Semaglutide is a potent long-acting glucagon-like peptide-1 (GLP-1) analogue that requires once-weekly administration. It is the main ingredient in some of the most popular weight-loss medications and is sold under brand names like:

• Ozempic
• Wegovy
• Rybelsus

Because semaglutide is more resistant than liraglutide to the degrading enzyme dipeptidyl peptidase-4 (DPP-4), it can be administered as a weekly dose [9].

How does semaglutide work?

Semaglutide is part of a drug group known as GLP-1 agonists, originally designed to help manage type II diabetes. These drugs encourage the pancreas to release more insulin, making them effective for type II diabetes, where some natural insulin production still exists. However, semaglutide isn’t suitable for type I diabetes, which lacks insulin production altogether [10].

During studies, researchers noticed that people taking semaglutide also tended to lose weight, as the drug reduced their appetite. This unexpected benefit quickly expanded its use in weight management, turning semaglutide into the top weight-loss medication of all time. However, semaglutide’s time at the top may be limited due to the introduction of tirzepatide or Mounjaro, which is not only a GLP-1 (glucagon-like peptide-1) agonist but also a GIP (glucose-dependent insulinotropic polypeptide) agonist, giving it dual action. This dual mechanism makes Mounjaro distinct from other GLP-1-only medications like Ozempic and Wegovy, as it targets both pathways to help control blood sugar levels and support significant weight loss.

The rise of Mounjaro is a story for a different day. For now, let’s return to semaglutide. By decreasing hunger and promoting a lower calorie intake, semaglutide supports gradual and sustainable weight loss.

Semaglutide, a GLP-1 analogue, is now known to curb appetite and enhance feelings of fullness, ultimately helping reduce food intake [11]. This effect works by activating GLP-1 receptors in the brain, indirectly influencing brain activity related to hunger, food choices, and overall energy intake [12].

The semaglutide clinical trials- The STEP program

A series of studies was conducted to assess the effectiveness and safety of semaglutide as a weight loss drug. These studies were called the STEP (Semaglutide Treatment Effect in People with Obesity) clinical trial program. They investigated the effects of a once-weekly, 2.4 mg subcutaneous dose of semaglutide, a GLP-1 (glucagon-like peptide-1) analogue, in overweight or obese individuals.

There have been 8 STEP programs designed to evaluate the effectiveness of once-weekly semaglutide injections (2.4 mg) for individuals with obesity or overweight. Each trial focused on a unique question:

• STEP 1: A primary study on weight loss results [13].
• STEP 2: A study examining weight loss impact in individuals with type 2 diabetes [14].
• STEP 3: A study looking at the combined effects of semaglutide and intensive behavioural therapy [15].
• STEP 4: A study examining the impact of continuing versus stopping semaglutide on maintaining weight loss over time [16].
• STEP 5: A study investigating long-term weight maintenance over two years [17].
• STEP 8: A study exploring a comparison of semaglutide with liraglutide for weight loss [18].

Additionally, the STEP 6 trial explored the effect of semaglutide on weight management among East Asian adults with and without type 2 diabetes, comparing results with a placebo [19].

These studies highlight the enormous scope for semaglutide in addressing weight management across various conditions and demographics. Based on findings from the STEP trials, a once-weekly injection of semaglutide 2.4 mg has gained approval in Canada, Europe, the UK, and the USA for long-term weight management in adults who are overweight (with related health conditions) or have obesity.

Why do you feel tired when taking semaglutide?

Wasn’t this what the blog was meant to be about in the first place? We have reached the point in the blog where I attempt to answer the original question. I apologise to all those who had to wade through the article to reach this point, but I bet you have learned a lot about semaglutide and Gila lizards.

Well, without further ado let’s explore if semaglutide does make you tired.

Research shows that people on semaglutide may lose up to 15% of their body weight [20]. However, this percentage can vary based on factors like your starting weight, existing health conditions, medications, and lifestyle choices.

The weight loss effect of semaglutide is mainly due to its ability to reduce appetite, making you feel less hungry. People tend to consume fewer calories with a lower appetite, leading to weight loss. However, eating less also causes the body to adjust by slowing metabolism, making you feel more sluggish or tired. This is one of the body’s nefarious devices to keep you at the same weight. You may be eating less, but you are also moving less. This is the body’s desperate attempt to keep you at your set weight.

Semaglutide affects blood sugar regulation by increasing insulin production and slowing digestion. While these effects are beneficial for managing blood sugar, they can sometimes lead to tiredness. Fortunately, lifestyle adjustments—like prioritising good sleep, exercise, and a nutritious diet—can help manage this fatigue.

Semaglutide fatigue is caused by a lack of essential nutrients and protein

This tiredness might also come from lower levels of essential nutrients. Vitamins like B-complex, Coenzyme Q10, and L-carnitine support energy production in the body, so without adequate intake, energy levels may dip.

Also, without sufficient nutrients, the body starts to break down fat and muscle. This is why it is crucial to include plenty of protein in your diet to prevent muscle loss and keep your body burning fat instead.

Common side effects of semaglutide—such as nausea, vomiting, and diarrhoea—can also add to fatigue, making it essential to approach the medication with good nutritional support and lifestyle habits.

How common is semaglutide fatigue?

In clinical trials for Wegovy (semaglutide), fatigue was reported as a side effect, though it was less common compared to others. According to prescribing information, around 11% of participants experienced fatigue, making it a secondary side effect compared to gastrointestinal issues like nausea (44%), diarrhoea (30%), and vomiting (24%) [21].

Feeling tired may be directly tied to the medication itself or could stem from other factors, such as changes in appetite, blood sugar regulation, and reduced calorie intake—all of which can sometimes lead to lower energy levels.

The jury is still out on why semaglutide may make you tired. It has been suggested that this is a side effect the body may experience as it gets used to the new drug. In this case, many people may experience initial fatigue, which gradually subsides as the body becomes accustomed to the drug.

The safety and side effects of semaglutide

The safety profile of once-weekly subcutaneous semaglutide 2.4 mg has been fairly consistent across the STEP clinical trials. The trials observed various types of adverse events (AEs), including serious AEs, AEs leading to discontinuation, and those occurring in over 10% of participants, mainly in the gastrointestinal (GI) category.

Key findings from the STEP Trials

• Gastrointestinal (GI) side effects: The most common side effects were GI-related, such as nausea, diarrhoea, vomiting, and constipation. These side effects were generally mild to moderate and often improved over time. GI issues led to slightly more discontinuations in the semaglutide 2.4 mg groups than in the placebo groups (0.8%- 4.5% vs. 0% -1.2 %) [22].
• Serious adverse events: Serious AEs were recorded but were relatively rare, with minor variations across different STEP trials. Some participants did experience serious events, though the overall safety profile remained consistent with known GLP-1 receptor agonist side effects [23]
• Cholelithiasis: The occurrence of gallstones (cholelithiasis) was consistent with known associations between rapid weight loss and gallbladder issues, previously linked to GLP-1Ras [24].
• Diabetic retinopathy: In STEP 2, diabetic retinopathy was reported in a small percentage of participants, with a slightly higher rate in the semaglutide 2.4 mg group than in the placebo [24].
• Comparing semaglutide and liraglutide: In STEP 8, rates of AEs, especially GI-related ones, were similar between semaglutide 2.4 mg and liraglutide 3.0 mg groups. However, fewer participants on semaglutide discontinued due to adverse events compared to those on liraglutide (3.2% vs 12.6%) [25]

Across the trials, there were no new safety concerns, and longer-term treatment with semaglutide 2.4 mg continued to demonstrate a stable safety profile.

Managing semaglutide fatigue: Helpful tips and strategies

Some users of semaglutide experience fatigue or tiredness. Although this side effect isn’t dangerous, it can interfere with daily activities. Here are practical tips for handling fatigue while on semaglutide:

1. Focus on quality sleep: Aim for 7-9 hours of restful sleep each night to fight fatigue. If sleep remains challenging, consult your healthcare provider for guidance or contact the team at Medical Mojo. If you’re having trouble sleeping, why not read our blog, 15 tips for healthy sleep? Or check out our compounded melatonin solutions.
2. Incorporate regular activity: A gentle walk or light exercise can help counter fatigue. Try to fit in at least 30 minutes of activity most days. It sounds counterintuitive, but it works.
3. Maintain a balanced diet: Eating a diet rich in fruits, vegetables, whole grains, and lean proteins can help maintain energy. Try to avoid processed foods and sugary snacks that might cause energy dips.
4. Take frequent breaks: Daily breaks can recharge your energy levels. Simple activities like stretching or a few moments of rest can be refreshing.
5. Consult your healthcare provider (or Medical Mojo!): If fatigue is persistent, talk to your doctor. They may adjust your dosage or recommend other strategies to manage your energy levels.

Supplements that may help with Semaglutide fatigue

• Vitamin B12: Important for red blood cell health and overall energy.
• Iron: Essential for oxygen transport; low levels can contribute to tiredness. But before you take an iron supplement, you must check your blood levels with your doctor.
• Magnesium: Supports energy production and helps reduce fatigue.
• Coenzyme Q10 (CoQ10) Plays a vital role in energy metabolism. Unfortunately, many Coenzyme Q10s are poorly absorbed. That’s why Medical Mojo has designed a compounded Coenzyme Q10 50mg in a soluble oral patch for enhanced absorption. This patch uses the buccal mucosa for direct access into the bloodstream, bypassing the gut.
• Omega-3 Fatty Acids: Help reduce inflammation and may support energy levels.

Purchasing Wegovy and Mounjaro weight loss injections from Medical Mojo

Medical Mojo offers Wegovy and Mounjaro weight loss injections, two effective medications for managing weight. If you’re looking for a safe and supportive weight loss journey, Medical Mojo provides these treatments at affordable prices, along with the option of a personalised lifestyle coaching service.

Complete the health questionnaire on Medical Mojo’s website to get started. This step ensures the treatment suits your unique health profile. Once completed, a licensed healthcare provider reviews your information and issues a prescription if appropriate. Each purchase has the option of dedicated support from a dedicated lifestyle coaching team, so you’re set up for long-term success.

Visit Medicalmojo.co.uk for the cheapest Wegovy and Mounajro weight-loss injections.

Did I mention that we are one of the most competitively priced online pharmacies offering Wegovy and Semaglutide?

Our prices for Wegovy and Mounjaro are:

• Wegovy 0.25mg injections – £125.99
• Mounjaro 2.5mg injections-£145.99

Visit Medical Mojo today to start your journey to better health. For the best rates on Wegovy and Mounjaro and a full range of supportive services, visit Medical Mojo today.

Professional guidance and supervision with Mounjaro from Medical Mojo

Before starting Mounjaro, please consult a healthcare professional like ours at Medical Mojo. They’ll provide guidance based on your health profile to confirm you’re a good candidate for the medication.

A comprehensive weight loss program with Medical Mojo includes:

• Clinically-proven medication: Prescription options like Wegovy and Mounjaro help manage hunger, reduce cravings, and slow digestion.
• FREE ongoing clinical support: Our clinicians will monitor potential side effects, make adjustments, and answer your questions throughout your journey.
• One-on-One Coaching: Join our lifestyle coaching program to receive support from nutritionists, exercise specialists, and behavioural coaches who provide tailored advice for sustainable lifestyle changes.

Medical Mojo’s take on semaglutide or Wegovy.

Wegovy is a valuable tool, not a quick fix. For the best results, use it alongside lifestyle adjustments. Misuse can pose health risks, so professional supervision and personalised coaching are essential for safe, effective progress.

For affordable weight loss injections and lifestyle coaching, complete the health questionnaire at Medical Mojo to get started today!

Disclaimer: This article is for informational purposes only and is not a substitute for professional medical advice.

Power up with Coenzyme Q10

Discover the benefits with our soluble oral patches

Learn more

References:

1. Mechanick JI, Hurley DL, Garvey WT. Adiposity-based chronic disease as a new diagnostic term: the American Association of Clinical Endocrinologists and American College of Endocrinology position statement. Endocr Pract. 2017; 23(3): 372-378.
2. Theilade S, Christensen MB, Vilsbøll T, Knop FK. An overview of obesity mechanisms in humans: endocrine regulation of food intake, eating behaviour and common determinants of body weight. Diabetes Obes Metab. 2021; 23(Suppl 1): 17-35.
3. Jensen MD, Ryan DH, Apovian CM, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Obesity Society. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63(25 Pt B):2985-3023. doi: 10.1016/j. jacc.2013.11.004.
4. Garvey WT, Mechanick JI, Brett EM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016; 22(Suppl 3): 1-203.
5. Singh AK, Singh R. Pharmacotherapy in obesity: a systematic review and meta-analysis of randomized controlled trials of anti-obesity drugs. Expert Rev Clin Pharmacol. 2020; 13(1): 53-64.
6. Alves, P.L., Abdalla, F.M.F., Alponti, R.F. and Silveira, P.F., 2017. Anti-obesogenic and hypolipidemic effects of a glucagon-like peptide-1 receptor agonist derived from the saliva of the Gila monster. Toxicon, 135, pp.1-11.
7. Astrup A, Rössner S, Van Gaal L, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009; 374(9701): 1606-1616.
8. Wadden TA, Hollander P, Klein S, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE maintenance randomized study. Int J Obes (Lond). 2013; 37(11): 1443-1451.
9. Blundell J, Finlayson G, Axelsen M, et al. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017; 19(9): 1242-1251.
10. Mishriky, B.M., Cummings, D.M., Powell, J.R., Sewell, K.A. and Tanenberg, R.J., 2019. Comparing once-weekly semaglutide to incretin-based therapies in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes & metabolism, 45(2), pp.102-109.
11. Friedrichsen M, Breitschaft A, Tadayon S, Wizert A, Skovgaard D. The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetes Obes Metab. 2021; 23(3): 754-762.
12. Gabery S, Salinas CG, Paulsen SJ, et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight. 2020; 5(6):e133429.
13. Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the treatment of obesity: key elements of the STEP trials 1 to 5. Obesity (Silver Spring). 2020; 28(6): 1050-1061.
14. Davies M, Færch L, Jeppesen OK, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021; 397(10278): 971-984.
15. Wadden TA, Bailey TS, Billings LK, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA. 2021; 325(14): 1403-1413.
16. Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021; 325(14): 1414-1425.
17. Garvey WT, Batterham RL, Bhatta M, et al. Two-year effect of semaglutide 2.4 mg once-weekly in adults with overweight or obesity (STEP 5): a randomized, double-blind, placebo controlled, phase 3 trial. Nat Med. 2022; in press.
18. Rubino DM, Greenway FL, Khalid U, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022; 327(2): 138-150.
19. Kadowaki T, Isendahl J, Khalid U, et al. Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2022; 10(3): 193-206.
20. Kosiborod MN, Bhatta M, Davies M, et al. Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: 1 and 4 exploratory analyses. Diabetes Obes Metab. 2023 ;25(2) :468-478. Doi:10.1111/dom.14890. https://pubmed.ncbi.nlm.nih.gov/36200477/
21. Novo Nordisk. (2021). Wegovy (semaglutide) injection, for subcutaneous use: Highlights of prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215256s000lbl.pdf
22. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021; 384(11): 989-1002. Bergmann, N.C., Davies, M.J., Lingvay, I. and Knop, F.K., 2023. Semaglutide for the treatment of overweight and obesity: a review. Diabetes, Obesity and Metabolism, 25(1), pp.18-35.
23. Stokes CS, Lammert F. Excess body weight and gallstone disease. Visc Med. 2021; 37(4): 254-260.
24. Davies M, Færch L, Jeppesen OK, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021; 397(10278): 971-984.
25. Rubino DM, Greenway FL, Khalid U, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022; 327(2): 138-150.