Can the exercise not only complement, but also to enhance the effects of pharmacological treatments? Is the weight the central variable in the improvement of the health of people with obesity? These questions, which we consider essential when addressing a lasting and significant change in the lives of patients, have led us to a process of reflection and research that culminated in the recent publication of the article entitled “ Metabolic Alliance: Pharmacotherapy and Exercise Management of Obesity ” In the prestigious Nature Reviews Endocrinology . 1 This article, which I had the honor of writing together with Dr. Jonatan R. Ruiz, highlights the synergy between exercise and medicines based on incredine as a strategy that can be revolutionary for obesity management.
Surely you have heard of the new drugs for obesity. The great revolution of the agonists of the peptide receptor similar to type 1 glucagon (LPG-1), such as the semaglutide, and the co-gonnists of the insulinotropic peptide receptor dependent on glucose (GIP) and GLP-1, such as the tirzepatide, It has arrived. These drugs have proven to be very effective in the loss of body weight, as demonstrated by the studies of the STEP and Pioneer for the Semaglutide, losing 16% of the weight, 2.3 and Surpass and Surmount for the Tirzepatide decreasing to 22.5% of the Weight, 4.5 making a great echo in the world press. But do they really serve exclusively to lose weight?
Figure 1 . Change in body weight with (a, b) semaglutide and (b) tirzepatide.
These drugs imitate the action of endogenous incredine hormones, modulating, among other things, appetite and energy intake. However, for years we know that obesity is a complex and multifactorial condition that requires an advanced and personalized approach to achieve sustained weight loss over time. In 2022, Wilding and collaborators observed that the interruption of treatment with agonists of the GLP-1 receiver could lead to a partial recovery of weight in people with obesity (Figure 2). 6 This highlighted the need to look for complementary strategies that could sustain the long -term benefits of these drugs.
Figure 2 . Change in body weight during the 68 weeks of study and later weeks, in which the group that took Semaglutide stopped using the medication. Adapted figure of Wilding et al. Diabetes OBES Metab . 2022.
With all this information, we begin to study the subject and find several works in the scientific literature that combined pharmacology (liraglutida) and exercise, improving the metabolism of glucose, glucagon and the function of pancreatic β cells, even in the improvement of inflammation at systemic level. 7.8 The answers to our questions were answered separately, but when analyzing the data, we observe that the well -planned exercise and the new drugs formed an effective metabolic alliance. It was only necessary to organize all the information and present it clearly, highlighting each idea and action separately. Above all, we wanted to call the scientific community to explore these promising approaches in obesity management without forgetting that prescribing the exercise is key in the health of the population.
Figure 3. Benefits of pharmacotherapy and exercise in obesity and human metabolism. Red indicates the benefits exercised by pharmacotherapy, while blue denotes the benefits of exercise. This figure highlights the holistic approach of integrating pharmacology for obesity with exercise to synargically improve metabolic health and treatment of obesity. Adapted figure of Butragueño, J. & Ruiz, JR 2024.
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One of the most significant improvements, in addition to reducing body weight, is that GLP-1 receiver agonists have shown the risk of myocardial infarction, stroke and death from cardiovascular diseases. For example, in studies with more than 17,000 patients with obesity and high cardiovascular risk, treatment with 2.4 mg of semaglutide during an average of 33 months reduced the risk of death due to cardiovascular disease, myocardial infarction or stroke in 20% in 20% in Comparison with placebo. 9
In this context, exercise is presented as a vital ally. This is demonstrated by its benefits: reduction of adiposity, improves aerobic capacity, vascular health and endothelial function, contributing to improve cardiovascular health and maintenance of long -term weight loss. Performing tissue adaptations can also be achieved, reducing blood pressure, increasing capillary density and improving the distribution of blood flow, which in turn improves the function of heart, pulmonary and muscular systems. 10
Final reflection
In summary, the combination of the new pharmacological treatments based on incredine, together with an individualized exercise prescription, could enhance metabolic effects, but more research studies are necessary reaffirming this hypothesis. For that reason, we conclude the article with a request to the scientific and medical community:
«Now is the appropriate time for medical societies and health groups to advocate the inclusion of exercise as complementary therapy to the pharmacological treatment of obesity in health centers. The tests on the metabolic benefits of both treatments necessary to take into account this metabolic alliance in the treatment of obesity«.
This article is a call to action, highlighting the importance of exploring and making the most of the potential benefits of combining the benefits of pharmacology and physical exercise. This union of forces is crucial to achieve increasingly effective and sustainable obesity.
References:
1. Butragueño, J. & Ruiz, Jr Metabolic Alliance: Pharmacotherapy and Exercise Management of Obesity. Nature Reviews Endocrinology 2024 1–2 (2024) DOI: 10.1038/S41574-024-01006-7.
2. Wilding, JPH et al. Once-Weekly Semaglutide in Adults with Overweight Or Obeesity. New England Journal of Medicine 384 , 989–1002 (2021).
3. Rodbard, HW, Dougherty, T. & Taddei-Allen, P. Efficacy of Oral Semaglutide: Overview of the Pioneer Clinical Trial Program and Implications for Managed Care. AM J Manag Care 26 , S335 - S343 (2020).
4. Jastreboff, Am et al. Tirzepatide eleven Weekly for the Treatment of Obesity. New England Journal of Medicine 387 , 205–216 (2022).
5. Wadden, ta et al. TIRZEPATIDE AFTER INTENSIVE LIFESTYLE INTERVENTION IN ADULTS WITH OVERWEIGHT OR OBESITY: THE SURMOUT-3 PHASE 3 Trial. Nat Med (2023) DOI: 10.1038/S41591-023-02597-W.
6. Wilding, JPH et al. Weight Regain and Cardiometabolic Effects After withdrawal of Semaglutide: The Step 1 Trial Extension. Diabetes OBES Metab 24 , 1553–1564 (2022).
7. Lundgren, Jr et al. Healthy Weight Loss Maintenance With Exercise, Liraglutide, Ort Both Combined. New England Journal of Medicine 384 , 1719–1730 (2021).
8. Jensen, SBK et al. Weight Loss Maintenance With Exercise and Liraglutide Improves Glucose Tolerance, Glucagon Response, and Beta Cell Function. Obesity 31 , 977–989 (2023).
9. Ryan, DH et al. SEMAGLUTIDE EFFECTS ON CARDIOVASCULAR OUTCOMES IN PEOPLE WITH OVERWEIGHT OR OBESITY (SELECT) RATIONE AND DESIGN. AM Heart J 229 , 61–69 (2020).
10. Ashcroft, SP, Stocks, B., Egan, B. & Zierath, Jr Exercise Induces Tissue-Specific Adaptations to Enhance Cardiometabolic Health. Cell Metab (2024).