How Does Stopping Semaglutide Affect Patients?

-By Dawn Sweet, Ph.D.

When patients stop taking semaglutide, health care providers should prepare them for possible withdrawal symptoms such as weight regain, increased appetite and food cravings, and the re-emergence of cardiovascular and metabolic risk factors.

Semaglutide is an effective pharmacotherapy for helping patients with obesity lose weight. Because semaglutide is not addictive, there are no withdrawal symptoms per se, but there are some risks and implications to take note of. Semaglutide withdrawal symptoms include weight regain, increased appetite and food cravings, and the possible re-emergence of cardiometabolic risk factors. Summarized below are some key considerations to discuss with patients once they stop taking semaglutide.

An Overview of Semaglutide Withdrawal Symptoms

• Weight Regain. A 2022 study¹ reports that, upon cessation of semaglutide, participants regained two thirds of the weight lost while taking weight loss medication. This study included 1,961 participants who were randomly assigned to a semaglutide treatment group (n = 1,306) and a placebo + lifestyle intervention group (n = 655). The semaglutide group began with a 0.25 mg dose and escalated to 2.4 mg over 16 weeks. The placebo + lifestyle intervention group were put on a 500 k/cal daily reduction and 150 minutes per week of physical activity. After 68 weeks, treatment was stopped. Subgroup analyses show that that those in the semaglutide group who experienced greater weight loss also experienced greater weight regain following the withdrawal of semaglutide.
• Increased Appetite and Food Cravings. Semaglutide has been shown to reduce appetite and increase feelings of satiety and fullness. In a randomized, double-blind control trial (n = 28) that consisted of two 12-week crossover treatment periods, participants were randomly assigned to a semaglutide-placebo or placebo-semaglutide treatment sequence with a 5 – 7 wash out period in between.² Semaglutide was dosed at 0.25 mg and then escalated to 1.0 mg. Participants taking semaglutide reported a decrease in appetite compared to the placebo group. Additionally, the semaglutide group reported better control of eating and fewer food cravings compared to the placebo group. Although participants were not tracked beyond the trial period, it is likely that once semaglutide is stopped food cravings will return and appetite control may not be as robust.
• Cardiometabolic health. Patients with obesity are at risk of developing cardiometabolic risk factors compared to health weight counterparts. When compared with a placebo, patients treated with semaglutide 2.4 mg saw improvements in cardiometabolic risk factors such as waist circumference, blood pressure, lipids, HbA1c, regardless of diabetes status, and CRP. Reversion to normoglycemia from prediabetes also occurred in the semaglutide group.³

How to Keep Weight Off After Patients Stop Taking Semaglutide

When patients stop taking semaglutide, it is important to talk with them about how semaglutide was connected to their weight loss, decreased appetite/food cravings, and improvements in cardiometabolic health. The gains achieved while taking semaglutide may not be fully sustained once stopping the medication (and may actually be reversed); however, patients can mitigate reverting to pre-semaglutide metrics by committing to lifestyle changes, including healthy eating, physical activity, and good quality sleep.

• Healthy Eating. Following the Dietary Guidelines for Adults⁴ is good point of departure for collaborating with patients on a healthy eating plan. The DGA offers guidance on caloric intake relative to energy expenditure as well as guidance based on age, gender, and portion sizes. The DGA provides guidelines for necessary macronutrients such as protein as well as novel suggestions to keep patients engaged in healthy eating.

• Physical Activity. Because successful weight loss is routinely paired with activity, health care providers should work with patients to develop sustainable exercise programs that include a variety of options such as resistance training or weight training, aerobic exercises, Pilates, and yoga. ^5,6,7,8
• Sleep is an oftentimes less considered strategy for weight loss and weight maintenance.^8,9 Poor sleep quality has been linked to type 2 diabetes, cardiovascular disease, and emotional eating, so working with patients to develop a sustainable sleep hygiene protocol can also benefit their post-semaglutide life. Sleep hygiene includes behaviors such as going to bed at the same time each night and getting up at the same time each day, removing electronic devices from your bedroom, and making sure your sleeping space is dark and quiet.¹⁰

Preparing Patients for their Lives Post-Semaglutide

Because the research on weight gain after stopping semaglutide, it is important to prepare patients for their lives post-semaglutide. Be sure to talk with patients prior to them going off semaglutide so that you have a workable and sustainable plan in place to managing diet, exercise, and sleep. Part of a healthy lifestyle following treatment with semaglutide should include nutritionally designed meal replacements that offer patients a convenient way to ensure they are consuming the necessary protein, fiber, vitamins, and minerals needed for nutritional health while giving them the energy they need to lead a physically active lifestyle.

Sources:

1 Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension

2 Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference, and body weight in subjects with obesity

3 Cardiometabolic risk factors efficacy of semaglutide in the STEP program

4 U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th Edition. December 2020

5 Resistance training effectiveness on body composition and body weight outcomes in individuals with overweight and obesity across the lifespan: A systematic review and meta‐analysis

6 Exercise preserves lean mass and performance during severe energy deficit: The role of exercise volume and dietary protein content

7  Psychophysiological adaptations to Pilates Training in overweight and obese individuals: A topical review

8 The National Sleep Foundation

9 Effect of exercise training on sleep apnea: a systematic review and meta-analysis

10 Centers for Disease Control and Prevention: Tips for better sleep

About the Author: Dr. Dawn M. Sweet has over 20 years of experience in the field of communication. Dr. Sweet has given several invited talks to and workshops for academic and private sector audiences on the role of nonverbal and verbal communication in achieving positive outcomes and mitigating bias. Her research has been published in several top ranked peer-review journals, and it has been featured on NPR’s River to River / All Things Considered, Buzzfeed, and Science Daily. Her research has also been used to inform expert testimony.