Comparison of an old appetite suppressor/metabolism enhancer and GLP-1 receptor agonists with their combined potential benefits in the short and long term focusing on healthy lifestyle choices in addressing obesity

This story does not include health advice. It is for information, inspiration, and awareness purposes.

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Over the last three decades, I wrote many articles about my research into the pharmacotherapy of obesity as a supplementary (jumpstart) approach to healthy lifestyle choices, but one piece of content reached a broader audience and even gained virality on NewsBreak showing the effectiveness of an old, almost forgotten drug. Here is the link to the article: Phentermine: An Old Drug That Brings New Hope for Obesity & Weight Management.

While I did not intend for the story to go viral and refrained from using sensational language, its adherence to scientific rigor and methodical principles based on experience and compelling case studies captured public interest and acceptance.

According to informed reviewers, the content resonated with a broad audience because this unique piece uncovered and shed light on a forgotten medication with extensive research spanning decades on the pharmacotherapy of obesity. The piece stood out as most weight loss articles from experts focused solely on recent drugs, ignoring the power of older ones.

In this short post, I aim to build on that foundation by exploring how combining an older medication with a new class of drugs, along with a healthy lifestyle, can provide a new avenue to address the obesity epidemic.

My story focuses on a dual approach to sustainable weight management: using medication as a jumpstart for those who need it but primarily emphasizing healthy lifestyle choices for sustainable results.

The obesity epidemic poses a significant public health challenge, necessitating a multifaceted approach to treatment. Medications like Phentermine and GLP-1 receptor agonists (GLP-1 RAs), such as Semaglutide and Tirzepatide, offer promising avenues for weight management through distinct mechanisms.

I also wrote about the promising and synergistic effects of GLP-1 receptor agonists on other debilitating conditions in a story titled GLP1-RAs: After Diabetes, Tirzepatide & Semaglutide Give Hope for Osteoarthritis & Dementia Patients.

To inform my readers of a comprehensive overview of GLP-RAs on NewsBreak. The article is titled "Leptin Therapy Historically Failed to Manage Obesity, Yet Research Into GLP1-RAs Brings New Hope."

Combining established and newer weight-loss medications, under careful medical guidance, may offer a more effective solution for some people struggling with obesity. However, it is important and necessary to weigh the potential benefits against possible risks with support from qualified healthcare professionals and always prioritize healthy lifestyle choices alongside any medication.

1 — Good Old Phentermine: Short-Term Appetite Suppression

Phentermine, a central nervous system stimulant, works by suppressing appetite and increasing metabolism. It mimics the effects of amphetamines, leading to reduced hunger and heightened energy expenditure.

Typically prescribed for short-term use alongside diet and exercise, Phentermine can be an effective tool for initiating weight loss. However, its side effects, including increased heart rate, insomnia, and nervousness, necessitate cautious use.

I won’t go into detail here as I wrote two stories about Phentermine, which can provide details for interested readers. Here are the links

Phentermine: An Old Medication Might Bring New Hope for Obesity Epidemic If Used Properly

Observation: Remarkable Effects of Phentermine in 9 Obese People in Last 6 Months

2 — New GLP-1 Receptor Agonists: Long-Term Metabolic Regulation

Semaglutide, Tirzepatide, Dulaglutide, Exenatide, and Liraglutide (GLP-1 receptor agonists) help regulate blood sugar levels, slow gastric emptying and promote feelings of fullness.

Various agents are available in the United States and Europe, each differing in efficacy, tolerability, dosing frequency, administration, and cost.These researchers in 2021, published in Therapeutic Advances in Endocrinology and Metabolism, reviewed phase III clinical trials and analyzed 14 head-to-head trials comparing agents like dulaglutide, exenatide, liraglutide, and semaglutide.

Results showed that while all GLP-1 RAs effectively reduce A1C, differences exist in their impact on A1C and weight and the frequency of adverse effects, providing insights into their unique advantages and disadvantages for type II diabetes management.

Used for chronic weight management and treatment of type 2 diabetes, Semaglutide or Tirzepatide offer sustained weight loss benefits with a favorable side effect profile, primarily involving gastrointestinal issues such as nausea and vomiting.

When studying metabolic hormones, I learned that glucagon-like peptide-1 (GLP-1) is a hormone produced in the intestines, specifically by specialized cells called L cells, in response to food intake. GLP-1 plays a specific role in regulating blood sugar levels. Let me summarize my knowledge of this unique and multifaceted hormone.

GLP-1 stimulates insulin secretion from pancreatic beta cells in a glucose-dependent manner. This means that GLP-1 is released when blood sugar levels rise after a meal, and it helps lower blood sugar by promoting glucose uptake into cells.

GLP-1 inhibits glucagon secretion, another hormone the pancreas produces. Glucagon typically raises blood sugar levels by promoting the release of glucose from the liver. By inhibiting glucagon secretion, GLP-1 helps to prevent excessive glucose production and release from the liver.

GLP-1 regulates appetite and food intake because it acts on the hypothalamus, a brain region involved in appetite control, to suppress appetite and reduce food intake. GLP-1 delays gastric emptying, contributing to feelings of fullness and satiety after meals.

Gastric emptying is the process by which food and liquids move from the stomach into the small intestine for further digestion and absorption before entering the bloodstream. I will cover gastric emptying in another story as it is a complex and comprehensive topic involving neural and hormonal signals and health conditions like gastroparesis, which is common in type II diabetes.

This NIH book chapter explains that Glucagon-like peptide-1 (GLP-1) agonists (also known as GLP-1 receptor agonists, incretin mimetics, GLP-1 analogs, or GLP-1 RAs) are a class of medications used to treat type 2 diabetes mellitus and in some cases, obesity. Examples of drugs in this class include tirzepatide, exenatide, lixisenatide, liraglutide, albiglutide, dulaglutide, and semaglutide.

Researchers increasingly favor glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for treating type 2 diabetes because they effectively lower A1C and weight with minimal risk of hypoglycemia and potential cardiovascular benefits.

3 — The Potential of Combined Therapy

Combining Phentermine and GLP-1 Receptor Agonists (GLP-1 RAs) could offer a comprehensive approach to weight loss, leveraging their distinct pathways.

Phentermine’s appetite suppression and metabolic boost, combined with GLP-1 RAs’ prolonged satiety and blood sugar regulation, might provide synergistic benefits.

Early studies and anecdotal reports suggest that this combination could enhance weight loss outcomes more effectively than either drug alone, potentially reducing the required doses and minimizing side effects.

4 — Balancing Risks and Benefits

Despite the potential benefits, the combined use of Phentermine and GLP-1 RAs requires careful consideration.

Both medications impact cardiovascular health, which could elevate the risk of adverse events when used together.

Rigorous monitoring and individualized treatment plans are essential to ensure patient safety. Further research is needed to confirm this combination's long-term safety and efficacy.

5 — Lifestyle Choices: A Pillar of Sustainable Weight Management

While medications can kickstart weight loss, sustainable management of obesity relies heavily on healthy lifestyle choices.

A balanced diet, regular physical activity, restorative sleep with rest, and other behavioral modifications are crucial for maintaining weight loss and improving overall health. Medications should complement, not replace, these foundational elements of weight management.

We also need to focus on environmental factors like toxins and pathogens and stress. You may check this old story titled Fat Loss Remains a Dream Unless We Manage Cortisol.

I also touched on other hormones impacting weight gain or weight loss in a story titled Watch Out for 9 Hormones If You Can’t Lose Fat Despite Your Efforts.

Conclusion and Takeaways: A Promising Path Forward

Combining Phentermine and GLP-1 RAs presents an intriguing possibility in the fight against obesity.

As researchers and healthcare providers continue to explore this potential, it remains vital to approach treatment holistically, integrating medication with lifestyle interventions. This dual strategy might address the physiological aspects of weight loss and promote long-term health and well-being.

The evolving landscape of obesity treatment emphasizes the importance of innovative approaches. Combining Phentermine and GLP-1 RAs under professional guidance may offer a powerful tool in our arsenal, but it must be coupled with a commitment to healthy living.

Together, these strategies can help people achieve meaningful weight loss and healthy weight management and ultimately improve their quality of life.

Metabolic health is tightly connected with mental health. From my experience and research, the most important factor affecting our overall health is insulin resistance. I want to highlight that insulin sensitivity is the key to a well-functioning metabolism. I wrote numerous stories about it that you may check out and understand this critical hormone indexed by Google in a list titled "Insulin Resistance and Sensitivity."

Further Reading

There are thousands of papers on weight loss and healthy weight management. From my reviews, the most useful one is a meta-analysis published in The Lancet in 2023.

This paper, titled “Pharmacotherapy of obesity: an update on the available medications and drugs under investigation,” covers the most powerful drugs, explaining their mechanisms and benefits, with citations from credible sources. It is available to the public.

The Lancet also provided an update in 2024 Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomized controlled trials.

Thank you for reading my perspectives. I wish you a healthy and happy life.

If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.