The good and bad sides of Ozempic®

The good and bad sides of Ozempic®

UPDATE DAY

A new drug is currently generating a lot of excitement for the treatment of type 2 diabetes. The weight loss generated is significant, but it is utopian to believe that it alone can put an end to the obesity epidemic. 

Ozempic® (or semaglutide) is a peptide that biochemically mimics the action of a hormone produced by the digestive system, namely GLP-1. This hormone greatly increases the production of insulin by the pancreas and therefore plays a crucial role in controlling blood sugar. 

Since GLP-1 is inactive in people with type 2 diabetes, administration of semaglutide has been shown to correct chronic hyperglycemia in these patients, leading to its approval as an antidiabetic drug. .

Appetite suppressant 

In addition to its effect on blood sugar, a very interesting property of GLP-1 is to reduce the appetite by slowing gastric emptying as well as by acting on certain neuronal circuits of the brain involved in the feeling of satiety.  

Since semaglutide mimics the action of GLP-1, this appetite suppressant effect is also observed in people treated with this drug: for example, one study reported that administration of semaglutide to obese people caused a decrease of 24&nbsp ;% of energy intake during the day, this drop in caloric intake being caused by a decrease in appetite and cravings and a reduction in the desire for high-fat foods.(1)< /p>

Clinical trials carried out subsequently showed that this reduction in the quantity of calories ingested was associated with very significant weight loss in the longer term: for example, obese people treated for 68 weeks lost an average of 15% of their initial body weight,(2) these losses even reaching 20% ​​in almost half of the participants.(3)  

These are considerable weight losses, of the same order greater than those typically observed following bariatric surgery. 

Pros and Cons 

These data raise the interesting possibility that semaglutide could represent a new pharmacological treatment for obesity. However, before getting too carried away, we must first consider the pros and cons of this new drug. 

The positive aspects&nbsp ;

1. Avoid surgery 

The magnitude of weight loss observed following treatment with semaglutide suggests that this drug may represent a viable alternative to bariatric surgery, an invasive procedure that is much riskier and does not always yield the desired results.&nbsp ;

This is particularly interesting for people suffering from morbid obesity and who are affected by several comorbidities, because the weight losses of the order of 20 % obtained as a result of treatment with semaglutide are sufficient to considerably reduce the risk of several pathologies associated with obesity (type 2 diabetes, hypertension, hepatic steatosis, cardiovascular accidents, sleep apnea).  

2. Finding balance with food  

It is the reduction in appetite produced by semaglutide that is responsible for the weight losses obtained with this drug, which shows how the significant increase in the number of overweight people observed in recent decades is caused by a overconsumption of food.  

Our brain, which has evolved over time to deal with food deficiency conditions, constantly seeks to maximize calorie intake and fiercely opposes any attempt to lose weight. 

These adaptations have certainly played an important role in the survival of our species, but they become totally dysfunctional in an environment where there is an overabundance of calories, as is the case today.  

Semaglutide therefore manages to interfere with these physiological adaptations and can therefore constitute for obese people a form of biochemical self-defense against the obesogenic environment in which they find themselves.

Aspects< /strong> negatives 

1. Side effects

A fairly large proportion of patients reported a number of side effects, particularly at the gastrointestinal level (nausea, vomiting, diarrhea, constipation). 

In clinical studies, where patients are closely supervised, these side effects have discouraged a fairly small number of people (5%), but it is likely that in 'real life', without ongoing support from a treating medical team, this number will be higher high.  

It should also be mentioned that preclinical results have identified a possible effect of the drug on the thyroid and it is recommended that patients who have a family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 syndrome avoid this medication.  

2. Reversibility of weight loss 

Currently available data indicate that discontinuing semaglutide treatment quickly leads to regaining most of the weight initially lost.(4) In other words, this suggests that treatment for obesity could be lifelong, much like d other pathologies such as hypertension or excess cholesterol. 

This is problematic because, on the one hand, the long-term side effects of this drug are not known and, on the other hand, the costs associated with these prolonged treatments would be staggering if they were administered on a large scale. It is estimated that 28% of the adult population of Quebec is obese, which corresponds to nearly 2 million people. Since a year of treatment with Ozempic® costs approximately $6,000 per person, treating these people would cost $12 billion annually, which is obviously well beyond the financial means of the state, for this condition alone. clinic. 

Ozempic® must therefore be seen above all as a drug of last resort to treat obese people at very high risk of complications resulting from being overweight and not as an antidote to the current obesity epidemic. The solution to this epidemic lies much more in prevention and healthy weight management than in pharmacological treatment. 

In this sense, absolutely everything must be done to curb obesity in children and adolescents. It is clearly established that it is extremely difficult to lose weight once obesity has set in metabolically and therefore intervention must be very early, before young people accumulate excess weight which puts them at very high risk of become obese in adulthood. We can therefore already see the consequences of our individual and societal laxity in the face of one of the worst pandemics in history, that of obesity.

(1) Blundell J 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: 1242-1251.
(2) Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity. N.Engl. J.Med. 2021; 384: 989-1002.
(3) Wadden TA et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity. JAMA 2021; 325: 1–11.
(4) Wilding JPH et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes. Metab. 2022; 24: 1553-1564.