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What happens when you stop weight loss injections?

Monday, August 12, 2024

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Weight loss injections like Wegovy (semaglutide) and Mounjaro (tirzepatide) are slowly overtaking weight loss tablets as the go-to treatments for managing obesity. These medicines behave like the natural hormones that control hunger (appetite), helping you feel fuller for longer, eat less food and lose weight.

But while weight loss injections are an effective way to shift extra weight, stopping treatment can cause rapid weight regain. In this article, we explore the effects of discontinuing weight loss injections, why weight gain may happen, and advice on managing your weight after stopping treatment.

How do weight loss injections work?

Weight loss injections are medicines that assist in weight loss by reducing appetite. They belong to a class of drugs known as GLP-1 receptor agonists (GLP-1s), which imitate the hormone GLP-1, a hormone that is naturally released by the gut after eating.

When released into the blood, GLP-1 slows food moving out of your stomach into your gut (delayed gastric emptying), meaning food stays in the stomach longer (1). It also signals the pancreas to release insulin to help regulate blood sugar and manage food cravings, as well as signal the brain’s appetite control centres to reduce feelings of hunger (1).

By acting like natural GLP-1, weight loss injections have the same effects on the stomach, pancreas, and brain to suppress appetite, reduce the amount of food a person eats and cause them to lose weight.

How well these medications work has been repeatedly demonstrated in studies. In a 2021 clinical trial, people using weight loss injection semaglutide (Wegovy) lost 15% of their weight over 68 weeks, compared to only 2% weight loss for the control group of people who were not using semaglutide (2).

A more recent 2024 study of semaglutide showed similarly impressive results in a real-world setting. After 3 months of injections, patients lost around 7% of their original body weight. By 6 months, weight loss had increased to an average of 12% (3).

What happens when you stop using weight loss injections?

Stopping weight loss injections causes several changes in the body, some of which can cause a regain of the lost weight. You won’t necessarily regain all of the weight lost with treatment, but some weight gain after stopping is normal.

One study found that participants regained two-thirds of the weight they had lost within a year after stopping semaglutide (Wegovy) (4).

Weight regain continued until the end of the study, at which point around half of the people involved couldn’t keep off 5% or more of their starting weight.

Other semaglutide studies show the same trend. One trial involving 800 participants found that weekly injections (combined with a diet and exercise plan) reduced weight by 11% within 4 months. However, when a third of the participants switched to a placebo, they regained 7% of the weight they had lost (5).

It isn’t only semaglutide that shows weight regain is a risk—it’s the same across all GLP-1s approved for weight loss. When patients stopped weekly injections of Mounjaro for weight loss (tirzepatide) and switched to a placebo, they gained 14% of their weight back (6). Likewise, a liraglutide (Saxenda) study reported weight gain in patients after stopping treatment (7).

Why do people regain weight after stopping GLP-1s?

Several factors contribute to weight regain after stopping GLP-1 injections:

  • Increase in appetite: Weight loss injections work by suppressing hunger (appetite). When you stop taking the medicine, this hunger-reducing effect diminishes. This increase in appetite causes increased food intake, which is thought to be the main reason for weight regain (8).
  • Metabolic changes: Weight loss injections help regulate blood sugar levels and improve metabolic function (9). When you stop the drugs, your metabolism may return to its pre-treatment state, affecting how your body processes food and stores fat.
  • Blood sugar control: For both people with type 2 diabetes and those who use treatment to manage weight, GLP-1 injections improve blood sugar control (10). Stopping the drugs can reverse these improvements, causing blood sugar spikes, an increase in cravings for sugary foods (11), and weight gain.

Interestingly, research shows that rapid weight regain after stopping semaglutide is more noticeable in those who have lost 20% or more of their starting weight (4). Another study on GPL-1 agonist liraglutide found that the more fat lost, the more likely patients were to regain some weight after stopping the drugs (7). The bigger the weight loss, the bigger the weight regain.

Why do people stop taking weight loss injections?

The current advice from Tier 3 and Tier 4 NHS Weight Management Services recommends staying on weight loss injections for up to 2 years. This recommendation aligns with the marketing authorisation limit (12), and the normal amount of time that patients remain in these services.

However, what happens for these patients after these 2 years has not been discussed. As stopping weight loss injections can cause weight gain, and obesity is a life-long condition, these drugs should not be seen as a quick fix. People should aim to stay on them indefinitely, but this is rarely the case.

People stop weight loss injections for several reasons:

  • Side effects: As with all medications, weight loss injections have side effects, which commonly include nausea, vomiting and diarrhoea, fatigue, and headaches. Researchers found that these side effects led to semaglutide discontinuation in 8% of patients (13).
  • Cost of injections: Some people may be entitled to receive drugs like Wegovy or Saxenda on the NHS for free, but only for 2 years. After this, patients need to pay around £240 per month for injections, which can cause excess financial strain.
  • Reached weight loss goals: Some people may believe they can maintain their new weight through diet and exercise without needing medication. This isn’t impossible, but our article highlights why understanding the risk of weight regain is so important for long-term weight management.

Advice on stopping weight loss injections

If you need to stop weight loss injections, remember that weight regain isn’t guaranteed. A large-scale study of 20,274 patients on semaglutide found that 3,588 returned to their starting weight within a year of stopping treatment, but more than half maintained or continued to lose weight (14).

Lifestyle factors likely impact the amount of weight regain. Most GLP-1 trials don’t continue with positive lifestyle changes, like eating a reduced-calorie diet and exercising more (15), after stopping injections, contributing to weight regain. While there is no research into the impact of maintaining healthy habits post-treatment, continuing them will likely help maintain a lower weight.

Weighing yourself regularly after stopping treatment can help you catch small weight gains early and adjust your lifestyle before the regain becomes significant. If you gain weight, remember that maintaining some weight loss is still a positive outcome.

The future of weight loss injections

There is a lot of research happening to both improve the effectiveness of weight loss injections and understand more about using them long term. A special project called SOPHIA at University College Dublin is learning about how to select the right treatments for a single individual, including things like blood and psychological tests. This could help identify the best drug and dosage for long-term weight management for a person first time.

But even with individualised treatments, most people will need to remain on the drugs for proper obesity management. Future studies will explore using higher GLP-1 doses during initial weight loss, followed by lower “maintenance” doses for long-term use. This could potentially reduce side effects and costs while maintaining effectiveness, making continued treatment more accessible.

Ultimately, lifelong use of these medications may be necessary to manage obesity effectively, and we will see a lot of new research over the next few years to help us better understand how to keep ourselves healthy when it comes to body weight.

References

  1. Shah M, Vella A. Effects of GLP-1 on Appetite and Weight. Reviews in Endocrine & Metabolic Disorders [Internet]. 2014 Sep 1;15(3):181–7.
  2. Wilding JPH, Batterham RL, Calanna S. Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine [Internet]. 2021 Feb 10;384(11):989–1002.
  3. Khaled Alabduljabbar, Alsaqaaby MS, Neff KW, Crotty M, Roux le. Weight Loss Response in Patients with Obesity Treated with Injectable Semaglutide in a Real-World Setting. Endocrine. 2023 Sep 21;
  4. Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, et al. Weight Regain and Cardiometabolic Effects After Withdrawal of Semaglutide: The STEP 1 Trial Extension. Diabetes, Obesity and Metabolism [Internet]. 2022 May 19;24(8):1553–64.
  5. Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, 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 [Internet]. 2021 Apr 13;325(14):1414–25.
  6. Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA [Internet]. 2023 Dec 11;331(1).
  7. A G, W AN, C le R. Long-term Weight Outcomes in Patients Treated with Liraglutide 3.0mg in Real-World Clinical Practice. Clinical Obesity [Internet]. 2023 Aug 24;
  8. What Happens When You Stop Taking Weight-Loss Drugs? [Internet]. www.bbc.com. [cited 2024 Jul 31].
  9. Alruwaili H, Dehestani B, le Roux CW. Clinical Impact of Liraglutide as a Treatment of Obesity. Clinical Pharmacology: Advances and Applications. 2021 Mar;Volume 13:53–60.
  10. Media Centre | EASD [Internet]. www.easd.org. [cited 2024 Jul 31].
  11. Yu JH, Shin MS, Kim DJ, Lee JR, Yoon SY ., Kim SG, et al. Enhanced Carbohydrate Craving in Patients with Poorly Controlled Type 2 Diabetes Mellitus. Diabetic Medicine: A Journal of the British Diabetic Association [Internet]. 2013 Sep 1;30(9):1080–6.
  12. 3 Committee Discussion | Semaglutide for Managing Overweight and Obesity | Guidance | NICE [Internet]. www.nice.org.uk. 2023 [cited 2024 Jul 31].
  13. Singh G, Krauthamer M, Bjalme-Evans M. Wegovy (semaglutide): a new weight loss drug for chronic weight management. Journal of Investigative Medicine [Internet]. 2021 Oct 27;70(1):jim-2021-001952.
  14. RN KB, MD CM, PhD JD, MD MG, Joyce B. Many Patients Maintain Weight Loss a Year After Stopping Semaglutide and Liraglutide [Internet]. epicresearch-prd.azurewebsites.net.
  15. Wilson K. Obesity: Lifestyle Modification and Behavior Interventions. FP essentials [Internet]. 2020 May 1;492:19–24.

Authored on 12 August 2024

Robert Bradshaw

Robert Bradshaw - MRPharms BSc(Hons) Pharmacy

Superintendent Pharmacist

GPhC Number: 2036118

Reviewed on 12 August 2024

Kiran Jones

Kiran Jones - MPharm, MRPharmS

Pharmacist / Medical Content Writer

GPhC Number: 2071585

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