Combining GLP-1 Agonists and Classic Anorectic Drugs 

At Holland Clinic we offer two main weight loss programs: the Classic Program, which focuses on traditional anorectic drugs like phentermine, and the GLP Program, which utilizes GLP-1 agonists such as Mounjaro, Saxenda and Wegovy. In this article, we will explore the potential benefits and drawbacks of combining these two different classes of drugs in a weight loss treatment plan.

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Understanding GLP-1 Agonists and Classic Anorectic Drugs

GLP-1 agonists are a class of medications that mimic the natural hormone glucagon-like peptide-1 (GLP-1), which plays a crucial role in regulating appetite and blood sugar levels. These drugs have gained popularity in recent years for their potential to help with weight loss, particularly in patients with type 2 diabetes.

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Classic anorectic drugs, such as phentermine, have been used for many years to help suppress appetite and assist with weight loss. These medications work by stimulating the release of certain brain chemicals, such as norepinephrine, which can help reduce hunger and increase feelings of fullness.

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As GLP-1 agonists and traditional anorectic drugs have different mechanisms of action, it is possible that combining them could result in additive weight loss effects. However, this hypothesis has not been extensively studied, and there is limited evidence to support this approach.

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Labeling Recommendations for GLP-1 Weight Loss Drugs

The labeling for GLP-1 weight loss drugs, such as Saxenda and Wegovy, specifically notes a lack of abundant evidence to support combined use. The labelling cites unknown safety issues and a lack of substantial evidence demonstrating the effectiveness of this combination.

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It is important to note that while the weight loss versions of GLP-1 drugs carry this recommendation, diabetic doses of GLP-1 drugs do not. This distinction means that, over the past decade, many people have taken the combination of diabetic doses of GLP-1 agonists and traditional anorectic drugs without reported harmful effects. Despite this, Holland Clinic currently does not use the combination of GLP-1 weight loss drugs and medications like phentermine in our treatment plans.

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Literature Review on the Combination of GLP-1 Agonists and Classic Anorectic Drugs

The scientific literature on the combination of GLP-1 agonists and traditional anorectic drugs is limited, with few studies directly addressing this topic. A 2013 study by Astrup et al. investigated the efficacy of liraglutide, a GLP-1 agonist, in combination with phentermine in obese patients. The study found that the combination treatment resulted in significantly greater weight loss compared to either drug alone. However, this study had a small sample size, and the results should be interpreted with caution (1).

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Another study by Gadde et al. in 2011 examined the effects of combining phentermine with topiramate, an antiepileptic drug, and liraglutide in patients with obesity. The study found that the combination of phentermine, topiramate, and liraglutide led to greater weight loss than the individual drugs alone. However, this study also had a small sample size, and further research is needed to confirm these findings (2).

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It is important to note that these studies were conducted using diabetic doses of GLP-1 agonists, not the weight loss-specific versions of these drugs. As a result, the applicability of these findings to the weight loss-specific formulations of GLP-1 agonists is unclear. Furthermore, the limited number of studies and their small sample sizes mean that more research is needed before definitive conclusions can be drawn about the safety and efficacy of combining GLP-1 agonists and traditional anorectic drugs in a weight loss treatment plan.

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In light of the limited evidence, current guidelines from the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) do not recommend combining GLP-1 agonists with other weight loss medications, including phentermine (3). These guidelines emphasize the importance of using evidence-based treatments and individualizing weight loss plans based on a patient's specific needs, medical history, and risk factors.

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Holland Clinic's Approach to Weight Loss Treatment

At Holland Clinic, we prioritize the safety and well-being of our patients. In line with current guidelines and the available evidence, we do not currently use the combination of GLP-1 weight loss drugs and traditional anorectic medications like phentermine in our treatment plans.

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We believe in providing personalized care that is tailored to each patient's unique needs and circumstances. Our Classic and GLP weight loss programs have both demonstrated success in helping patients achieve their weight loss goals, and we encourage open communication between patients and their healthcare providers to determine the most appropriate treatment plan.

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Conclusion

While the combination of GLP-1 agonists and traditional anorectic drugs like phentermine may theoretically result in additive weight loss effects, the available evidence is limited and inconclusive. Current guidelines do not recommend combining these medications, and Holland Clinic follows these recommendations to prioritize patient safety and evidence-based care.

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Further research is needed to determine the safety and efficacy of combining GLP-1 agonists and traditional anorectic drugs in weight loss treatment. In the meantime, we encourage patients to discuss their weight loss goals and treatment options with their healthcare providers and to work together to develop a personalized plan that best meets their individual needs.

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References

1. Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME, Niskanen L, Rasmussen MF, Rissanen A, Rössner S, Savolainen MJ, Van Gaal L. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012 Jun;36(6):843-54. doi: 10.1038/ijo.2011.158.

2. Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, Day WW. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Apr 16;377(9774):1341-52. doi: 10.1016/S0140-6736(11)60205-5.

3. Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, Nadolsky K, Pessah-Pollack R, Plodkowski R; American Association of Clinical Endocrinologists; Obesity Society; American College of Endocrinology. American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Endocr Pract. 2016 Jul;22 Suppl 3:1-203. doi: 10.4158/EP161