The global prevalence of overweight and obesity has reached alarming levels, with nearly 40% of adults being overweight and 13% obese. This excess weight carries significant health consequences, including cardiovascular diseases, type 2 diabetes, dyslipidemia, and increased mortality. While numerous strategies exist for treating obesity, each comes with its own set of challenges and considerations.
The Challenge of Obesity: A Multifaceted Problem
Obesity, as defined by The Obesity Society (TOS), is a multi-factorial chronic disease resulting from excess fat accumulation that poses a risk to health. It affects multiple organ systems, leading to additional chronic diseases. The varied treatment responses observed in individuals with obesity likely stem from our limited understanding of the mechanisms of weight regulation.
Understanding the "Set Point" Theory
The concept that body fat storage may be regulated was first proposed by Kennedy et al. through the concept of a “set point.” This theory suggests that adipose tissue may produce a signal sensed by the brain to target a "level of body fatness." Despite its influence, the molecular mechanisms behind the set point theory remain ambiguous, making the development of effective pharmacologic treatments challenging.
The Role of the Gastrointestinal System
In the last 20 years, the gastrointestinal system has been identified as the largest endocrine organ, demonstrating the key role of gut hormones in energy homeostasis. The discovery of the gut hormone glucagon-like peptide-1 (GLP-1) and the synthesis of agonists for its corresponding receptor (GLP-1 receptor) has significantly impacted treatment for weight reduction.
Current Treatment Strategies for Obesity
Treating obesity has evolved with various dietary, pharmacological, and surgical strategies.
Read also: Weight Loss Guide Andalusia, AL
Dietary Approaches
Dietary advice has historically focused on energy restriction as the foundation for weight loss. While numerous studies have shown that dietary macronutrient composition is not the most significant contributing factor for weight loss, guidelines have started to include a more nuanced understanding that there is a synergy between dietary nutrients and their food sources.
- Low-Fat Diets: The low- or very-low fat intake approach is recommended for inducing significant short-term weight loss, but its long-term efficacy is not superior to dietary interventions with higher fat content.
- Low-Carbohydrate Diets: The low carbohydrate diet involves consuming a low content of carbohydrates and a high content of fat and protein. It is especially suitable for individuals with type 2 diabetes and/or insulin resistance. However, exceeding 6-12 months of use may have undesired effects by increasing LDL cholesterol and cardiovascular risk in some studies.
- The Mediterranean Diet: The Mediterranean diet, rich in plant-based food with high dietary fiber and antioxidants, has a higher composition of fatty acids, unlike the conventional Western diet. In addition to its effect on body weight, it has favorable effects on heart and brain health and decreased diabetes risk.
Pharmacological Interventions
- Orlistat (tetrahydrolipstatin): Orlistat inhibits pancreatic lipases, reducing fat absorption in the intestine and promoting weight loss. Patients are advised to consume a low-fat diet to combat the side effects of oily stool. This drug leads to a weight loss nadir at around 36 weeks with a weight regain that happens at around 52 weeks. However, the weight regain is relatively mild and by 104 weeks there is still overall weight loss.
- Contrave (bupropion/naltrexone): Contrave appears to modulate appetite and reward centers. A weight loss plateau seems to occur for all the COR studies around 32 to 36 weeks with overall weight loss around 8 to 9%.
- Qsymia (phentermine/topiramate): Qsymia appears to induce satiety and reduce hunger. It has demonstrated overall efficacy for weight loss maintenance, achieving sustained weight loss of 9-10% at the 108-week mark compared to 1.8% for placebo.
Surgical Interventions
- Intragastric Balloon: The intragastric balloon is a temporary and minimally invasive therapy that reduces stomach capacity and results in decreased hunger and food intake. A silicone balloon is endoscopically deployed and filled with saline and inflated for 6 months.
- Bariatric Surgery: Bariatric surgery is indicated in patients with a BMI above 40 independent of coexisting comorbidities or in patients with a BMI over 35 with a history of comorbidities such as type 2 diabetes or hypertension. There are two common procedures currently used: sleeve gastrectomy and gastric bypass. Emerging evidence suggests that the sleeve procedure is associated with few reoperations, but significant regain of weight while the bypass procedure can lead to more durable weight loss and glycemic control.
GLP-1 Receptor Agonists: A New Frontier in Weight Loss
GLP-1 medications have revolutionized weight loss, potentially reducing body weight in obese patients by 15% to 25% on average after about 1 year. They mimic the endogenous GLP-1, an intestinal hormone that regulates glucose metabolism and satiety.
Mechanism of Action
GLP-1 is a hormone released from the enteroendocrine cells of the small intestine in response to food intake. It stimulates insulin secretion, suppresses glucagon secretion, slows gastric emptying, and increases satiety. GLP-1 receptor agonists mimic these effects, leading to improved blood sugar control and weight loss.
Potential Benefits and Risks
While GLP-1 drugs offer promising results, they also carry known risks and potential unforeseen risks.
- Known Risks: GLP-1 drugs carry a boxed warning for people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Gastrointestinal adverse events (nausea, vomiting, diarrhea) are fairly common, while pancreatitis and intestinal obstruction are rarer. There may be a loss of lean body mass as well as premature facial aging.
- Weight Regain: A significant disadvantage of using these medications is the high rate of weight regain when they are discontinued.
Long-Term Considerations
Based upon the “set point” theory of weight regulation, the possibility of needing these medications over extended periods to avoid inevitable weight regain may cause clinicians to consider other treatments. The lack of long-term clinical trials in weight management compels clinicians to consider potentially unforeseen long-term side effects of the GLP-1 receptor agonists.
Read also: Beef jerky: A high-protein option for shedding pounds?
The EVIDENT 3 Application: A Mobile Health Intervention for Weight Loss
Mobile technology is increasingly being used in medicine for prevention, diagnosis, and treatment of chronic diseases, including obesity. The EVIDENT 3 application is designed to promote healthy living habits and assess its impact on weight loss when combined with traditional primary care lifestyle modifications.
Study Design and Objectives
The EVIDENT 3 study is a randomized, multicentre clinical trial with 2 parallel groups conducted in a primary care setting. The study aims to assess the impact of the EVIDENT 3 application on weight loss when combined with traditional primary care lifestyle modifications in overweight or obese subjects. Secondary outcomes include changes in physical activity, sedentarism, caloric intake, quality of life, arterial aging, and pro-inflammatory markers.
Methodology
Participants will be randomly assigned to either the intervention group (IG) or the control group (CG). Both groups will receive traditional primary care lifestyle counseling prior to randomization. The subjects in the IG will be lent a smartphone and a smartband for a 3-month period, corresponding to the length of the intervention. The EVIDENT 3 application integrates the information collected by the smartband on physical activity and the self-reported information by participants on daily food intake.
Outcome Measures
The primary outcome will be weight loss (kg). Secondary outcomes will include change in physical activity (steps/d) measured by accelerometer, sitting time (min/wk), caloric intake (kcal/d), quality of life, arterial aging, and pro-inflammatory markers.
The Importance of Physical Activity and Lifestyle Modifications
A healthy lifestyle has been associated with a lower prevalence of obesity. Regular physical activity plays an essential role in preventing chronic diseases, including cardiovascular disease, obesity, diabetes mellitus, osteoporosis, and colon cancer. Sedentarism, defined as low levels of energy expenditure, is related to multiple health problems, including a higher risk of diabetes, cardiovascular disease, cancer, and all causes of death.
Read also: Inspiring Health Transformation