GLP-1 Agonists in the Battle Against Obesity: A Comprehensive Overview of Benefits, Risks, and the Evolution of Weight Loss Strategies
Over the past century, numerous medical-assisted weight loss strategies have emerged to combat the rising rates of obesity. In the 1940s, amphetamines were approved after observing weight loss in narcolepsy patients being treated with the drugs (1). Amphetamines stimulate the body to burn calories faster and can curb behaviors that lead to weight gain. However, due to their temporary effects, the risk for addiction is high, and amphetamines are less common. In the 1950s, phentermine, an amphetamine-derived anorectic agent, emerged. In combination with fenfluramine, the drug, commonly called fen-phen, stimulates the hypothalamus to encourage appetite restriction. Due to discoveries that fenfluramine caused harm to heart valves, fen-phen was pulled, but phentermine still remains available (2). In addition to drugs, bariatric surgery remains a viable option. This is performed when lifestyle changes or medical treatments have not helped a patient lose weight. These surgeries involve reshaping or removing a part of the stomach to reduce the amount of food consumed, helping the patient to lose weight (3). In recent years, a new type of strategy has surged on the market: GLP-1 agonists. GLP-1 agonists were originally approved for the treatment of Type 2 diabetes due to their ability to regulate blood sugar and stimulate insulin production (4). Yet now, with the approval of Wegovy for obesity, health care providers have begun prescribing GLP-1 agonists as a treatment strategy, shifting how medicines can help weight loss (5).
GLP-1 agonists mimic glucagon-like peptide-1 (GLP-1), a naturally occurring hormone produced after food intake that increases insulin production and reduces glucagon production, the hormone that raises blood sugar (6). After food is consumed, GLP-1 interacts with the satiety hormone leptin to signal the brain to trigger feelings of fullness (6). The use of GLP-1 agonists imitates this process to encourage satiation and slows the rate of gastric emptying, thus making people feel fuller longer (6). GLP-1 agonists were first evaluated and approved as a treatment strategy for Type 2 diabetes after understanding the role of GLP-1 on blood sugar regulation. However, because weight loss was observed in diabetic patients using GLP-1 agonists, studies examining them have shown that GLP-1 agonists can be used as a treatment for obesity, eventually leading to the FDA’s approval of the dosage branded as Wegovy for obesity treatment in 2021 (7).
Potential Health Benefits of GLP-1 Agonist Use
GLP-1 agonists and its associated weight loss have multiple health benefits. Losing weight can improve mobility by reducing inflammation around any aching joints, leading to more comfort in daily activities (8). Weight loss can also reduce the risk of diseases like Type 2 diabetes in predisposed patients, as well as potential cancers or diseases by reducing inflammation around vital organs (8). Using GLP-1 agonists has also been shown to be correlated with improvements in cardiovascular health (9). Studies examining patients who lost weight with GLP-1 agonists reported lower blood pressures and moderately reduced cholesterol levels (9). A reduction in blood pressure and cholesterol helps to improve cardiovascular health by lowering the risk of cardiovascular events like heart disease or stroke (9). However, it is important to note that there is currently not enough data to determine whether these benefits, especially cardiovascular improvements, are a result of using GLP-1 agonists or the associated weight loss (9).
Potential Pitfalls of GLP-1 Agonist Use for Medical-Assisted Weight Loss
Like with any treatment, the use of GLP-1 agonists does carry side effects (5). The most commonly reported side effects are nausea, vomiting, and diarrhea, ranging from mild to significant in severity levels– continued GLP-1 agonists use may also increase the risk for pancreatitis and renal disease (10). Consideration of the side effects is important as GLP-1 agonists are also only going to help keep any weight off as long as the drug is being used. Studies published in JAMA reported that patients who lost weight with GLP-1 agonists regained much of it back after stopping treatment following the trials’ conclusions (10). Because of this and the classification of obesity as a chronic disease, GLP-1 agonists are approved for long-term, even life-long weight management (5). This means that any side effects and risks associated with the drug may persist for however long the patient is on the medication. To emphasize, recent studies examining adherence (based on available longer-use data from Type 2 diabetes studies) show significant declines: for example, 47.7% and 70.1% of people stopped the use of GLP-1 agonists at 12 and 24 months, respectively (13). Whether this is due to cost, requirement for self-injection, side effects, or other reasons remains to be studied. Because GLP-1 agonists as weight loss treatment is a relatively new approach, there is currently insufficient time and research to reveal any long-term effects (either positive or negative) of the medication.
Holistic Health as Part of GLP-1 Agonist Use
While GLP-1 agonists can be used as a monotherapy, clinical treatments often incorporate other strategies, like lifestyle changes or other agents, in addition to using GLP-1 agonists. Dietary changes, either nutritional changes or reductions in caloric intake, are usually a part of the weight management strategy in addition to GLP-1 agonists (11). Regular physical activity is also included since a portion of the weight lost with GLP-1 agonists is often muscle mass (12). Insulin prevents the synthesis of muscle proteins; GLP-1 agonists stimulate insulin secretion, meaning muscle mass can be lost due to insufficient protein absorption. Because of this, it is necessary that regular exercise is part of the treatment strategy in addition to the use of GLP-1 agonists in order to stimulate protein synthesis and maintain that muscle weight (14). Dietary and exercise strategies have to be taken into consideration when prescribing GLP-1 agonists because it means the patient is likely going to have to make some sort of lifestyle change and maintain that for the duration of their treatment.
With this information in mind, current evidence supports that GLP-1 agonists are a viable option for treating obesity as long as its use and side effects are carefully monitored by health professionals (12). Because there is not much known about the effects after long term use, especially in patients who are not diabetic, consistent follow-up appointments and monitoring of body systems is vital to ensuring the safety of the patient. It should be noted that because GLP-1 agonists are intended for long term use, they should be prescribed to patients whose quality of life would significantly improve through treatment. Although the evidence of adherence to GLP-1 agonists suggests a real-world challenge for long-term use, it also presents an opportunity to consider hybrid strategies.
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References
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