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How do weight loss injections help you lose weight?

Unveilling the mechanics behind GLP-1 based medical pens, their benefits, and side effects. Dive into the role of GLP-1 hormones in aiding weight loss

Azeem Yussouf
Azeem Yussouf
Medical doctor
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How do weight loss injections help you lose weight?

You’ve probably seen them in the news, read about them in the paper, or even know someone who uses them. Weight loss injections like Wegovy are becoming ever more popular as tools for weight loss, and with new contenders being developed as we speak, these medications are definitely here to stay.

But how exactly do these medical pens help you lose weight?

That’s the question we’ll be exploring in this article. Read on to learn how they work, how to use them, and what their benefits and side effects are.

But first, we need to understand a very important term when we discuss these medications; Hormones, and specifically GLP-1 hormones.

GLP-1 hormones explained

When we talk about health and wellbeing, we quite often hear the word ‘hormone’, which is either doing something really good to us or causing a lot of trouble. 

So what is this, in the first place? 

A hormone is a chemical substance that plays a major role in regulating several physiological processes within the human organism. Hormones are produced and released by numerous cells located all over the body1. Each hormone carries a message (signal), which is passed to an organ, muscle, or other tissues through the bloodstream. To appropriately read the message, a receiving cell of the tissue must have a receptor, another chemical substance, which accepts the signal and acts on it by inducing certain changes in the cell's activity. Our digestive system has various hormone producing cells, whose activity is affected by food we are eating.

Glucagon-like peptide 1 (GLP-1) is one of these hormones, which is produced and released from cells covering the lining of the bowel (particularly, distal small intestine and large intestine - ileum and colon) in response to certain macronutrients (carbohydrates [glucose] and fat [fatty acids]) 2-4

How weight loss injections work

Naturally produced and released GLP-1 hormone has a very short half life (1-2 min) due to rapid inactivation by DPP 4 enzyme.

In addition, only around 10-15% of native GLP-1 goes into systemic circulation and reaches a receiver (a cell [tissue, organ] with the GLP-1 receptor within it), which all together limits its potential and efficacy 2,5

The new generation of weight loss drugs

Liraglutide (Saxenda), semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro [in conjunction with GIP hormone]) are all artificially synthesised GLP-1 receptor agonists [GLP-1 RA], which have different chemical structure compared to a native version, thus providing greater efficacy and longer action.

Some studies indicated that individuals living with obesity and/or glucose metabolism impairment (including type 2 Diabetes Mellitus) have reduced natural GLP-1 secretion levels in response to ingested food compared with the healthy subjects. 

Improving metabolism with GLP-1

GLP-1 RA (liraglutide, semaglutide and tirzepatide) could potentially improve the metabolic health of an individual, and, as a result, restore the natural function of GLP-1 hormone 6-9

In addition, some dietary adjustments, such as adding slow release carbohydrates (resistant starch or dietary fibres), complete protein (containing all essential amino acids) and unsaturated fats (plant, fish oil), will not only provide a body with all necessary nutrients, but also decrease glycaemic load of the meal, thus slow down glucose absorption into bloodstream and improve endogenous (naturally produced by our body) GLP-1 efficacy 5.

Where GLP-1 works in the body

GLP-1 receptors (signal ‘receivers’) are located in the central and peripheral nervous systems, pancreas, gastrointestinal tract, cardiovascular system, kidneys, lung, and even skin 2,4,10. Wide distribution of this receptor within the body explains the diversity and importance of its activity.

Both, GLP-1 and GIP belong to a group of hormones called ‘incretins’, which are modulating blood glucose metabolism 2,4,5,11

How GLP-1 treatments help

The mechanism of action involves pancreas stimulation to increase production of insulin (a hormone directly involved in glucose metabolism regulation by promoting glucose utilisation by cells), which aims to maintain a normal blood glucose level 12. In addition, GLP-1 suppresses glucagon (a hormone stimulating glucose production in the liver if blood sugar levels are very low) secretion from pancreas  cells 13

First GLP-1 RA (exenatide, 2005) was approved for use to improve glycemic (blood glucose) control for individuals living with type 2 Diabetes Mellitus 14. Due to additional effects, such as slowing down gastric emptying and suppressing appetite via brain anorexigenic (reduced appetite) signals, individuals on GLP-1 RA therapy consumed less calories (reduced food intake) resulting in considerable weight loss. Considering a beneficial outcome of the treatment related to weight management, GLP-1 RA was also approved for the treatment of obesity (liraglutide [Saxenda] in 2014, semaglutide [Wegowy] in 2021 and tirzepatide [Mounjaro] in 2023) 14,15

However, both indications of GLP-1 therapy (blood glucose management and chronic weight management) are approved only as an adjunct to a healthy diet and adequate/increased physical activity. 

Heart health and GLP-1

In addition to weight control and positive metabolic effects, recent study results showed GLP-1 RA therapy has a beneficial impact on the cardiovascular system, in particular, reduced risk of adverse cardiovascular events (acute myocardial infarction, stroke, and cardiovascular mortality) by 20% 16.

How to use weight loss injections? 

Weight management GLP-1 RA medicines are currently available in a form of subcutaneous (fatty layer just beneath the skin) injections, which are slowly and steadily diffusing into a bloodstream via small blood vessels. 

First generation GLP-1 RA (liraglutide [Saxenda]) is injectable once daily, other two (semaglutide [Wegovy] and tirzepatide [Mounjaro]) once weekly. That provides a sustainable circulation of GLP-1, resulting in a continuous appetite control (as long as medication is taken). 

The volume of each single dose is less than 1 ml and the needle itself is very fine and short (around 4-6 mm), which makes the medicine injection barely noticeable. 

However, some sensitivity, redness and bruising (haematoma) at the injection site might be expected. 

There are 3 areas where you can inject these drugs:

- Upper arm

- Thigh

- Lower abdomen

You can choose any of these sites as location won’t impact medicine effectiveness. Our nurses at Embla will always assist with the injection when needed, and we also provide support if any side effects or adverse reaction occur.

Are weight loss injections safe?

Like all medicines, GLP-1 RA (liraglutide, semaglutide and tirzepatide) can cause side effects, but not everyone will necessarily get them.

Here are symptoms registered by patients reached maximum dose of 2.4mg semaglutide (Wegovy) during the 68 weeks of treatment:

- Very common (≥1 in 10) - nausea, vomiting, abdominal pain, diarrhoea, constipation, headache, fatigue

- Common (≥1 in 100 to ≤1 in 10) - abdominal distention, dyspepsia, gastroesophageal reflux disease (GERD), gastritis, eructation (belching), flatulence, cholelithiasis (gallstones), diabetic retinopathy (patients with diabetes type 2), hypoglycaemia (patients with type 2 diabetes), hair loss, dizziness, injection site reactions

- Uncommon (≥1 in 1000 to ≤1 in 100) - hypotension/orthostatic hypotension, increased heart rate, acute pancreatitis, delayed gastric emptying, increased amylase and lipase (under investigation)

- Rare (≥1 in 10000 to ≤1 in 1000) - angioedema, anaphylactic reaction

Other GLP-1 RA medicines, such as liraglutide (Saxenda) and tirzepatide (Mounjaro) can cause the same side effects with some minor difference in the occurrence possibility rates. The symptom severity and frequency will depend on the medicine dose, treatment length and personal tolerability.

There is also a potential risk of pancreatic and medullary thyroid gland cancer, however the association between these types of cancer with the use of GLP-1 RA medicines has not been established yet and needs further evaluation.

As per national recommendations, a maintenance dose is achieved after a slow increase (each 4 weeks) to17-19:

- 3 mg liraglutide [Saxenda] (daily injection)

- 2.4 mg semaglutide [Wegovy] (weekly injection)

- 15 mg tirzepatide [Mounjaro] (weekly injection)

The original trials on GLP-1 RA efficacy had shown the following results:

- Saxenda 3 mg after 56 weeks of intervention - 5.2% of weight loss20;

- Wegovy 2.4 mg after 68 weeks of intervention - 12.4% of weight loss21;

- Mounjaro 15 mg after 72 weeks of intervention - 17.8% of weight loss22.

EMBRACE III 2023 study has shown that Embla members achieved 15.3% mean weight loss while using 60.7% less medication (semaglutide [Wegovy]) over the course of 40 weeks, which highlights the importance of lifestyle modification as a crucial part of the sustainable and effective weight loss process, rather than relying solely on the medication effect. Lower dose of medication also reduces the risk of the side effect occurring, thus providing a safer approach to lose weight without compromising its efficacy23

Do weight loss injections work?

The main idea of the GLP-1 RA is to reduce the appetite at the level which will help to control the overall amount of food consumed during the day.

Controlling appetite for weight loss

 It is achieved by being able to control the portion size of the meal and have less craving episodes, which leads to reduced total calorie intakes. The higher dose doesn’t result in a greater weight loss, as it occurs as a result of the calorie deficit (when our body uses more energy than it consumes) rather than a direct effect of the medication. 

An optimal dose adjustment is essential, as the weight loss process should be as comfortable and sustainable as possible. Slow, but steady weight loss will give more chances of keeping the long-term results 24.

The evolution of GLP-1 RA medications

New generation GLP-1 RA, such as tirzepatide (Mounjaro), works by the same mechanism as previously approved weight loss medicines (liraglutide [Saxenda], semaglutide [Wegovy]). However, a presence of GIP hormone in tirzepatide enhances GLP-1 RA activity, thus providing a greater appetite suppressing effect 25.

There are several mechanisms within our body, which impact our appetite regulation and eating behaviour with the aim to promote and maintain homeostasis (stability). Certain foods (solid foods high in protein and/or fibre) naturally promote quicker satiation and longer satiety, preventing us from excess energy intake26

Eases lifestyle changes

Nevertheless, being distracted by the social and environmental influence, we are continuously challenged to rely purely on our body’s self-regulation, which sometimes prompts a certain eating behaviour resulting in a weight gain. Weight loss medication helps to reduce this environmental pressure, making it easier to alter lifestyle changes leading to an improved quality of life, including a healthy weight. However, to make these positive changes, you must have support from the specialist who will guide you in the right direction towards a healthier version of yourself.

Why the path to lasting weight loss requires more than medication 

The truth is that the only way to lose weight is to eat fewer calories than the body is using. 

Sounds simple, right? 

However, based on the previous ‘dieting’ experience, medical history, sex, age, body composition (fat vs fat free mass ratio) and daily physical activity level, the amount of energy a body is using will considerably differ between individuals. 

Also, certain eating behaviours, habits or beliefs could prevent you from achieving and maintaining a healthy weight. 

Medication alone won’t teach you on lifestyle adjustments needed for a healthy weight and overall well-being, it won’t help to create a good relationship with food long term. For this reason it's essential that you work on your lifestyle for lasting success. This is where Embla comes in.

At Embla we are actively working on all aspects of our member health and environment to find a personalised approach, which provides a comfortable and stress-free weight loss progress and a sustainable result. We titrate medicine as per our member requirements, which helps to reach a weight goal with the minimal risk to health.

References:

  1. Cleveland Clinic [Internet]. [cited 2023 Aug 17]. Hormones: What They Are, Function & Types. Available from: https://my.clevelandclinic.org/health/articles/22464-hormones
  2. The Physiology of Glucagon-like Peptide 1 [Internet]. [cited 2023 Aug 17]. Available from: https://journals.physiology.org/doi/epdf/10.1152/physrev.00034.2006
  3. Hoyt EC, Lund PK, Winesett DE, Fuller CR, Ghatei MA, Bloom SR, et al. Effects of fasting, refeeding, and intraluminal triglyceride on proglucagon expression in jejunum and ileum. Diabetes. 1996 Apr;45(4):434–9.
  4. Tachibana T. Subchapter 26C - Glucagon-like peptide-1. In: Ando H, Ukena K, Nagata S, editors. Handbook of Hormones (Second Edition) [Internet]. San Diego: Academic Press; 2021 [cited 2023 Aug 18]. p. 239–41. Available from: https://www.sciencedirect.com/science/article/pii/B9780128206492000632
  5. Hira T, Trakooncharoenvit A, Taguchi H, Hara H. Improvement of Glucose Tolerance by Food Factors Having Glucagon-Like Peptide-1 Releasing Activity. Int J Mol Sci. 2021 Jun 21;22(12):6623.
  6. Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012 Dec;8(12):728–42.
  7. Sharma D, Verma S, Vaidya S, Kalia K, Tiwari V. Recent updates on GLP-1 agonists: Current advancements & challenges. Biomedicine & Pharmacotherapy. 2018 Dec 1;108:952–62. 
  8. Jensterle M, Rizzo M, Haluzík M, Janež A. Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review. Adv Ther. 2022;39(6):2452–67.
  9. Anandhakrishnan A, Korbonits M. Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity. World J Diabetes. 2016 Dec 15;7(20):572–98. 
  10. Zhao X, Wang M, Wen Z, Lu Z, Cui L, Fu C, et al. GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects. Frontiers in Endocrinology [Internet]. 2021 [cited 2023 Aug 18];12. Available from: https://www.frontiersin.org/articles/10.3389/fendo.2021.721135
  11. Cho YM, Kieffer TJ. Chapter Four - K-cells and Glucose-Dependent Insulinotropic Polypeptide in Health and Disease. In: Litwack G, editor. Vitamins & Hormones [Internet]. Academic Press; 2010 [cited 2024 Feb 15]. p. 111–50. (Incretins and Insulin Secretion; vol. 84). Available from: https://www.sciencedirect.com/science/article/pii/B9780123815170000047 
  12. National Institute of Diabetes and Digestive and Kidney Diseases [Internet]. [cited 2023 Aug 18]. Insulin Resistance & Prediabetes - NIDDK. Available from: https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance
  13. Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. Cell Metabolism. 2018 Apr 3;27(4):740–56. 
  14. Latif W, Lambrinos KJ, Rodriguez R. Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Aug 18]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK572151/
  15. GOV.UK [Internet]. [cited 2024 Feb 15]. MHRA authorises diabetes drug Mounjaro (tirzepatide) for weight management and weight loss. Available from: https://www.gov.uk/government/news/mhra-authorises-diabetes-drug-mounjaro-tirzepatide-for-weight-management-and-weight-loss
  16. American College of Cardiology [Internet]. [cited 2023 Aug 21]. SELECT: Semaglutide Reduces Risk of MACE in Adults With Overweight or Obesity. Available from: https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2023/11/09/15/04/select#:~:text=Prior%20studies%20of%20lifestyle%20and,to%20this%20increased%2Drisk%20population. 
  17. Liraglutide | Drugs | BNF content published by NICE [Internet]. [cited 2024 Feb 13]. Available from: https://bnf.nice.org.uk/drugs/liraglutide/
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  20. Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015 Jul 2;373(1):11–22. 
  21. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2021 Mar 18;384(11):989–1002.
  22. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022 Jul 21;387(3):205–16.
  23. McCormack JP, Allan GM, Virani AS. Is bigger better? An argument for very low starting doses. CMAJ. 2011 Jan 11;183(1):65–9. 
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  25. Samms RJ, Coghlan MP, Sloop KW. How May GIP Enhance the Therapeutic Efficacy of GLP-1? Trends in Endocrinology & Metabolism. 2020 Jun 1;31(6):410–21.
  26. Benelam B. Satiation, satiety and their effects on eating behaviour. Nutrition Bulletin. 2009;34(2):126–73.

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Azeem Yussouf
Azeem Yussouf
Medical doctor
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