Regaining Weight After Semaglutide Weight Loss with Ozempic, Zepbound, Mounjaro and Wegovy: How to Prevent

Presently, of the one-third of Americans who are obese, an estimated 50%–70% are trying to lose weight. While losing weight is difficult for many people, even more challenging is to keep the weight off. Most people who lose a large amount of weight regain the weight in 2 to 3 years. In addition, the improvements observed in blood sugar, blood pressure and other co-comorbidities of obesity found with weight loss diminish as the weight is gradually regained.

Weight Regain After Weight Loss is Normal Metabolic Process

This weight regain after weight loss is a physiologic process and not the result of lack of willpower, motivation or poor adherence to the plan. The typical response is for the dieter to think he is lazy or incapable of permanent weight loss. Unfortunately, this is often reinforced by health care practitioners who are sure the dieter is “cheating” on the plan.

The graphs below show the typical weight regain after  weight loss. The graph on the left shows the  weight loss over 14 weeks after stopping the weight loss medications despite the type of diet used. Note the very similar weight loss-weight regain patterns no matter how the weight loss was obtained. This is observed  even with the new semaglutides on the graph on the right represented by the “placebo” group:

Comparison of low carb vs low fat weight loss  weight loss with Wegovy over 98 weeks

A key determinant of  weight regain is the balance between ingested calories and the body’s energy expenditure. Obesity results when small positive energy balances accumulate over a long period of time. This balance involves both internal and external factors:

Weight Regain after Diet:  Due to Hormonal and Metabolic Changes 

1. Hormonal changes cause weight re-gain:

The reduction in free leptin, increase in ghrelin (hormone encouraging eating) and changes in peptide YY (hormone released from pancreas reducing appetite) and GIP (gastric inhibitory peptide) occur with weight loss encouraging eating and weight regain. The body interprets even modest weight loss as starvation and makes adaptations in hormones that increase appetite and decrease satiety (fullness) to “help” the body regain  initial weight. Exercise and “healthy eating” is  not enough to prevent this almost “normal” response to weight loss. The appetite increase over baseline results in eating about an extra 45 calories per lb of lost weight per day. That  is not much, but think of the extra calories after a typical 20 lb weight loss. (45 lb x 20 =900 calories extra per day!).No exercise plans can keep up with this daily ingestion of excess calories.

Slowing of Metabolism, termed adaptive thermogenesis causes weight re-gain:

Slowing of metabolism, more than would be predicted by weight loss alone with decrease in energy expenditure of about 10-15 calories a day contributes to the weight gain but not nearly as important as the hormonal factors which may four times as much.

These hormonal and metabolic changes help explain the common observed pattern of early rapid weight loss that plateaus after several months, followed by slow, but progressive weight regain. Different weight loss plans yield different results but the overall patterns are similar. As people lose more and more weight they fight a battle that encourages weight regain. Often the dieter is unable to recognize this increase in appetite and food consumption because studies have shown that signals to the brain are  below the level of consciousness. Food portions get larger and selections become higher in calories and carbs very slowly. Making recognition of this problem even more difficult is the fact that they happen slowly and relentlessly often over years.

Although the  the factors causing weight regain are internal to the body, there are a few external forces that contribute to the battle that results in weight re-regain.

metabolism falls with weight loss

Weight Regain Due to Environment and Lack of Physical Activity after Weight Loss

  1. External factors responsible for weight regain after weight loss:increasing environment with exposure to high density highly caloric foods which are inexpensive and easy to get results in mindless eating, grazing, bingeing and night eating. The result is the consumption of high calorie, high carb foods and snacks often with no easy control. Ultra-processed foods now contribute to most of foods eaten in the US. Fewer people prepare meals at home and more food is in restaurants or take-outs.

2. Limit in physical activity. Occupations have become more sedentary, with more driving and less walking. Taken together the changes in food and physical activity tend to drive people to increase intake of food and decrease activity. The net is weight gain rather than weight loss.
The idea that exercising an hour a day and burning 3500 calories over a week, or reducing food intake by 500 calories a day for a week will result in a 1 pound loss of weight is mistaken. Researchers have shown that this calculation is incorrect because it fails to take into account the reduced energy expenditure that occurs with substantial weight loss.

All four of these factors act together to produce weight regain after weight loss. This is observed whether the weight loss is accomplished by simple caloric reduction with increase exercise, by anti-obesity weight loss medications-both old and new, and even by the Semaglutides-Ozempic, Wegovy and Mounjaro.

Weight Loss and Regain with Semaglutides and Wegovy

Increasing numbers of patients are turning to semaglutide medications as an effective treatment for their obesity. Many of these have noted marked weight loss of 20 to even 35% of their starting weight. Additionally, substantial numbers of patients with hypertension, diabetes, hyperlipidemia, and obstructive sleep apnea note improvement or even complete resolution of these conditions with weight loss, even in a few months. The table below presents the average weight loss and regain observed after stopping various types of therapy including diet and exercise alone, typical anti- obesity therapy with phentermine or Qsymia, therapy and even with the three semaglutides compared to Bariatric surgery:

  Weight Loss and Regain After Obesity Therapy

Intensive
diet/exercise
Anti Obesity
medication
OzempicWegovyZepbound

Mounjaro

Bariatric
Surgery 1
Average weight loss from baseline   3-8%   5-10%     13%  17%21-27%25-30% @
1-2 ys
Average weight
regain.   No meds.
   2-3%   7%11% in 1 yr66% in
48 wks
 25-40%

Preventing Weight Regain

Weight gain can be prevented after weight loss by continuing the weekly Semaglutide injection reached  during the weight loss phase. Due to availability and costs i have had hundreds of my patients reduce the frequency of injections to twice a month or even once a month and still maintain the weight. It appears that the dose for maintenance may be much lower than the dose for weight loss in many individuals.