Breakthrough Obesity Drugs

Could dieting become obsolete?

In the past 50 years, the prevalence of obesity has tripled. Being significantly overweight increases the chances of developing various health issues like type 2 diabetes, heart disease, and several malignancies.

The need for the creation of efficient obesity treatments is growing as obesity rates rise.

New hormone-mimicking pharmaceuticals may reduce hunger and encourage weight loss regarding the advancement and possibility of novel treatments for obesity.

It may reduce the cause of experiencing emotions of guilt and the stigma associated with being overweight.

GLP-1 receptor agonists, which have been biochemically designed to increase potency and have a sustained effect, are successfully used in clinical settings to treat type-2 diabetes.

The GLP-1 analogue Semaglutide was initially licensed by the US FDA to treat type 2 diabetes, but was later approved as a medication to treat obesity.

In a trial, semaglutide users dropped an average of roughly 16% of body weight, more than twice as much as those on an earlier weight-loss medication.

Other potent anti-obesity drugs are currently being researched and developed, including tirzepatide and retatrutide.

How do these drugs work?

The complex hormone glucagon-like peptide-1 (GLP-1) has a wide range of therapeutic applications, as shown both in humans and animals:

• Glucose-dependent stimulation of insulin secretion
• Delaying of stomach emptying
• Suppression of food intake
• Alleviation of spatial memory dysfunction and learning
• Potential target for psychostimulant abuse
• Cardio- and neuroprotective effects
• Reduces inflammation and apoptosis (a form of programmed cell death)

These mechanisms of action, as well as how they affect appetite control and weight loss, are still being studied.

These medications are thought to function by simulating hormones that suppress the appetite and induce feelings of fullness, which lower the amount of food consumed.

In patients with Inflammatory Bowel Disease (IBD) and type 2 diabetes, a lower risk of adverse clinical events was observed amongst patients treated with GLP-1 based therapies.

These findings suggest that treatment with GLP-1 based therapies may improve the disease course of IBD.

A recent study showed that semaglutide treatment resulted in a 20% decrease of major adverse cardiovascular events over a period of up to five years. These events included cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke.

GLP-1 receptor agonists are effective and tolerable for antipsychotic-associated body weight gain. The use of these medications for psychiatry patients has grown so much that some physicians are considering drafting a standard approach paper for the staff on prescribing them.

Despite the positive clinical trial outcomes, not everyone responds to the medications in the same way. How each person reacts can vary depending on their genetics, lifestyle, and starting weight.

These drugs’ long-term effects and safety are still being studied.

Short-term adverse effects like nausea and vomiting have been noted in certain cases. Most reported side effects were:

• Nausea (44%)
• Diarrhea (30%)
• Vomiting (24%)
• Constipation (24%)
• Abdominal pain (20%)
• Headache (14%)
• Fatigue (11%)

Researchers are convinced that the treatments can be safe over long periods of time based on prior experience with similar pharmaceuticals used to treat type 2 diabetes, even though long-term usage may pose potential dangers.

Novo Nordisk, the manufacturer of semaglutide and liraglutide, remains confident in their benefit-risk profile and committed to patient safety despite reports of suicide or self-harm cases.

Social and economic perspectives

Based on existing data, it is unknown if glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, are cost-effective as therapies for obesity and type 2 diabetes.

Potential modifications in the future might boost their economic viability. Beyond reducing drug costs, a more thorough cost-analysis is needed, including treatment’s broader effects, such as pain, disability, depression, and societal expenses.

People who are physically active are less likely to become obese, regardless of how much they consume. For populations receiving appropriate nutrition, activity level is a more fundamental determinant of body weight than food is.

Patients who are stuck in a never-ending cycle of exercise and dieting seek something more practical with a more certain effect.

A practical substitute is a prescription for medication.

The enthusiasm among scientists and doctors for these new medications’ potential to treat obesity is clear, but there are also worries about potential side effects and societal repercussions.

Some fear that the availability of these drugs could exacerbate eating disorders. Then, promoting health awareness beyond weight should be emphasized.

Studies reveal the expanding research and interest in these novel obesity drugs, but it also raises concerns about individual reactions, long-term safety, and societal and economic repercussions.

References

Nature. News feature 02 August 2023 . Four key questions on the new wave of anti-obesity drugs. McKenzie Prillaman. Nature 620, 28–30 (2023). doi: https://doi.org/10.1038/d41586-023-02445-4

Nature. News Explainer 10 August 2023. Anti-obesity drug also protects against heart disease — what happens next? Mariana Lenharo. https://www.nature.com/articles/d41586-023-02528-2

Villumsen M, Schelde AB, Jimenez-Solem E, Jess T, Allin KH. GLP-1 based therapies and disease course of inflammatory bowel disease. EClinicalMedicine. 2021 Jun 23;37:100979. doi: https://doi.org/10.1016%2Fj.eclinm.2021.100979

Müller TD, Finan B, Bloom SR, D’Alessio D, Drucker DJ, Flatt PR, Fritsche A, Gribble F, Grill HJ, Habener JF, Holst JJ, Langhans W, Meier JJ, Nauck MA, Perez-Tilve D, Pocai A, Reimann F, Sandoval DA, Schwartz TW, Seeley RJ, Stemmer K, Tang-Christensen M, Woods SC, DiMarchi RD, Tschöp MH. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019 Dec;30:72–130. https://doi.org/10.1016%2Fj.eclinm.2021.100979

Medscape. Drugs & Diseases. Semaglutide (Rx) https://reference.medscape.com/drug/ozempic-rybelsus-wegovy-semaglutide-1000174#4

News. Medscape Medical News. Evidence Weighed for Suicide/Self-Harm With Obesity Drugs. Lori Youmshajekian. July 12, 2023 . https://www.medscape.com/viewarticle/994266

News. Medscape Medical News. Conference News. ADA 2023. Affording the Cost of New Obesity Drugs? We Can’t Afford Not to. Mitchel L. Zoler, PhD. July 21, 2023. https://www.medscape.com/viewarticle/994266