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Obesity has been reported to be one of the most common threat to our health in the last decades. This complicated chronic condition develops after long-term positive calorie balance causing excessive expansion of adipose tissues and ectopic fat accumulation, increasing the risk of other diseases such as cardiovascular disease, type 2 diabetes, stroke, and cancer in both adults and children. Several research institutes and pharmaceutical companies are focussing their efforts in highlighting the molecular mechanisms which lead to the development of this condition, as well as in developing more efficient treatments to minimize the issue correlated to this condition. In this article we are going to discover some statistics around obesity and some of the new strategies adopted to help patients suffering from this condition.

Some numbers about obesity

In 2024, the NCD Risk Factor Collaboration (NCD-RisC) estimated in their annual report that more than one billion people worldwide are currently living with obesity, of which nearly 880 million adults and 159 million children and adolescents aged 5-19 years. Childhood obesity, in particular, has received noteworthy attention in recent years, as this has shown a 10-folds increase in around 50 years time. Although a high number of young boys in the determined age range developed this condition, no difference between young boys and young girls have been observed.

In adults, obesity rates nearly tripled among women (6.6% to 18.5%) and quadrupled in men (3% to 14.0%) between 1975 and 2022. This is the equivalent of approximately 504 million women and 374 million men living with obesity in 2022.

Biological and socio-economical causes of obesity

Although biology plays an essential role in the development of this condition, several biological and physiological factors influence the development of this condition.

The human body is designed with an important defence system to prevent starvation, by protecting our body fat. Through the production of an important hormone called leptin, the brain receives signals related to how much fat is stored in our body. When fat levels fall and leptin decreases, the brain interprets this situation as starvation and switches the metabolism mode to energy saving, and changes appetite to increased hunger and decreased fullness. By this way, the brain prevents our body weight from falling, but in presence of extra fat, the weight loss is limited. This happens because when we try to lose weight, fat and leptin levels fall and the body increases hunger, decreases fullness and conserves energy, leading to a weight regain. Monitoring weight, eating regular and healthy meals and engaging in daily physical activity can help with dealing with the biological problems related to obesity.

The reduction of highly processed, calorie-dense, nutrient-poor food consumption also helps with decreasing the risk of developing obesity. This problem used to be more common in the Western diets, due to a combination of appealing packaging and extensive marketing, associated with brain appetitive control systems that increase appetite, food motivation, and food reward value. Nowadays in many low- and middle-income countries processed food increased due to their reduced costs compared to healthier meals.

Additionally, another biological cause of obesity is related to the genetic set we inherit from our parents. Our genes account for somewhere between 40-70% of the likelihood of having obesity, although they are not enough to lead to obesity development alone, but they need the influence of environmental factors.

Finally, recently several studies have reported connections between mental health issues and obesity. Some mental health disorders can have symptoms such as lethargy, decreased sleep, excessive sleep, and increased appetite, which can lead to weight gain. Some treatments for mental health disorders (e.g. antidepressant and antipsychotic medication) have been associated with moderate to significant weight gain. However, this connection is bidirectional, as people with obesity are at a higher risk of developing depression and anxiety. Factors contributing to this include social stigma and discrimination, poor quality of life and poor body image.

Pharmacological treatments against obesity

Pharmacological treatments for obesity are currently available due to their increasing demand and they combine changes in patients' lifestyle (including diet and exercise) with prescription medications working by affecting appetite or how the body absorbs fat. Several options are currently available on the market, and they come from different providers.

Liraglutide, semaglutide and tirzepatide are all GLP-1 receptor agonists which increase insulin sensitivity and secretion, suppress glucagon secretion, and slows gastric emptying. GLP-1 is a naturally occurring hormone that helps control blood sugar and appetite. As GLP-1 receptors agonists, all these drugs help the body release more insulin, lowering blood sugar, slow the digestion process and suppress the appetite.

Other drugs often used to treat obesity are orlistat, bupropion-naltrexone and phentermine-topiramate, mostly used for chronic weight control management.

However, all of these drugs may show several side-effects, and this is why currently several efforts are being made in researching better options for treating obesity with new drugs showing higher efficacy and less side effects.

Future directions of pharmacotherapy against obesity

The plethora of available drugs to treat obesity, together with the new currently under investigations, creates the unique challenge for physicians to decide which medication may be most appropriate for the individual patient. Selection of the appropriate therapeutic approach should be based on safety and tolerability, comorbidities, and accessibility. Physicians should avoid medications for which the patient has contraindications or is at risk of intolerability due to the medications side effect profile, target treatment to multiple comorbidities when possible, taking advantage of medications that have dual indications and strategically combine medications with complementary mechanisms.

All of this can be reached by treating obesity via a comprehensive approach to understand and control the roots of this chronic condition.

References

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NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet. 2024 Mar 16;403(10431):1027-1050. doi: 10.1016/S0140-6736(23)02750-2. Epub 2024 Feb 29. PMID: 38432237; PMCID: PMC7615769.

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