Obesity GLP-1 Drugs for winder use

We have all heard or know of someone who is taking an obesity drug, but the exciting news is that research is going to extend approval of GLP-1 drugs for wider use. A summary of GLP-1 is in the general post on Ozempic and GLP-1 Drugs here.

GLP-1 Not Just for Obesity and Type 2 Diabetes

Glucagon-like peptide-1 (GLP-1) receptor agonists have garnered considerable interest in recent years due to their multifaceted roles beyond glycemic control in type 2 diabetes mellitus (T2DM). Emerging evidence suggests that these agents may confer therapeutic benefits in reducing inflammation and improving clinical outcomes in various diseases, including heart disease, liver disease, kidney disease, autoimmune conditions, and dementia. This short review synthesises findings from recent clinical and observational studies, exploring how GLP-1 receptor agonists could extend their therapeutic reach into these diseases.

Heart Disease

Heart disease and kidney disease are among the most extensively studied domains for GLP-1 receptor agonists outside of diabetes management. Various studies have demonstrated their efficacy in reducing major adverse cardiovascular events and improving renal outcomes. For instance, systematic reviews and meta-analyses have consistently reported favourable cardiovascular outcomes with GLP-1 receptor agonists in comparison to other glucose-lowering treatments, highlighting reductions in cardiovascular mortality and myocardial infarction risk (Caruso et al. 2022; Mosenzon, Schechter, and Leibowitz 2021; Górriz et al. 2020). Additionally, their renoprotective effects in diabetic kidney disease, characterised by reduced albuminuria and slowed progression of renal dysfunction, reflect their significant potential beyond glycemic control in managing diabetic complications (Toimil and Ciudin 2021; Mosenzon, Schechter, and Leibowitz 2021; Holliday, Frost, and Navaneethan 2024).

Liver Disease

In liver disease, particularly nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), GLP-1 receptor agonists have shown promise in improving liver histology and reducing liver enzyme levels, although results across studies have varied. Meta-analyses and clinical trials often highlight improvements in liver inflammation and fibrosis markers, suggesting GLP-1 receptor agonists as potential therapies for NAFLD/NASH (Malik et al. 2022; Mantovani et al. 2021; Mantovani and Targher 2021; Lv et al. 2020). However, treatment response inconsistencies and study design variances indicate the need for further refined investigations to characterise these effects.

Autoimmune and Dementia

Research into autoimmune diseases and dementia is more exploratory, with initial observations indicating potential benefits. In autoimmune diseases, observational studies report possible cardiovascular benefits and inflammatory marker modulation (Karacabeyli et al. 2023; 2024). Similarly, in the context of dementia, some preliminary studies propose the potential for GLP-1 receptor agonists to mitigate dementia incidence, although clinical evidence remains nascent (Nørgaard et al. 2022).

Overall, the expanding research landscape suggests GLP-1 receptor agonists possess significant potential in managing a range of inflammatory and degenerative conditions beyond their traditional role in diabetes treatment. Future research must focus on consolidating these findings through targeted clinical trials to understand better the therapeutic potential of GLP-1 receptor agonists in these domains.

Obesity GLP-1 Drugs for Wider Use publications over past decade
Publication map relevance to advances in other uses for GLP-1 drugs

Weight Loss Range

Ozempic and relative body weight change
Data range https://yourlocalepidemiologist.substack.com/p/curious-about-ozempic-heres-the-lowdown

Side Effects

side effects with Ozempic drom Ghusn et al

Other Targets for Weight Loss

There are over 32 hormones involved in hunger and satiety so expect to see other drugs in this research field. Here are just 14 of them.

Table 1 from Marks et al. [14]

References

  1. Caruso, I., A. Cignarelli, G. Sorice, A. Natalicchio, Sebastio Perrini, L. Laviola, and F. Giorgino. 2022. “Cardiovascular and Renal Effectiveness of GLP-1 Receptor Agonists vs. Other Glucose-Lowering Drugs in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Studies.” Metabolites. https://doi.org/10.3390/metabo12020183.
  2. Evans, Marc, P. Kuodi, C. Akunna, Nicole McCreedy, Morten Donsmark, Hongye Ren, and C. Nnaji. 2023. “Cardiovascular and Renal Outcomes of GLP-1 Receptor Agonists vs. DPP-4 Inhibitors and Basal Insulin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.” Diabetes & Vascular Disease Research. https://doi.org/10.1177/14791641231221740.
  3. Górriz, J., M. Soler, J. Navarro-González, C. García-Carro, M. J. Puchades, L. D’Marco, A. Martínez Castelao, et al. 2020. “GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists.” Journal of Clinical Medicine. https://doi.org/10.3390/jcm9040947.
  4. Holliday, Michael W., L. Frost, and S. Navaneethan. 2024. “Emerging Evidence for Glucagon-like Peptide-1 Agonists in Slowing Chronic Kidney Disease Progression.” Current Opinion in Nephrology and Hypertension. https://doi.org/10.1097/MNH.0000000000000976.
  5. Karacabeyli, D., Diane Lacaille, Na Lu, N. McCormick, Hui Xie, Hyon K. Choi, and J. Aviña-Zubieta. 2024. “Mortality and Major Adverse Cardiovascular Events after Glucagon-like Peptide-1 Receptor Agonist Initiation in Patients with Immune-Mediated Inflammatory Diseases and Type 2 Diabetes: A Population-Based Study.” PLOS ONE. https://doi.org/10.1371/journal.pone.0308533.
  6. Karacabeyli, D., N. Lu, N. McCormick, H. Choi, D. Lacaille, and J. Aviña-Zubieta. 2023. “OP0025 MORTALITY AND MAJOR ADVERSE CARDIOVASCULAR EVENTS AFTER GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST INITIATION IN PATIENTS WITH AUTOIMMUNE DISEASES AND TYPE 2 DIABETES: A POPULATION-BASED STUDY.” Annals of the Rheumatic Diseases. https://doi.org/10.1136/annrheumdis-2023-eular.2163.
  7. Lv, Xiaodan, Yongqiang Dong, Lingling Hu, Feiyu Lu, Changyu Zhou, and S. Qin. 2020. “Glucagon‐like Peptide‐1 Receptor Agonists (GLP‐1 RAs) for the Management of Nonalcoholic Fatty Liver Disease (NAFLD): A Systematic Review.” Endocrinology, Diabetes & Metabolism. https://doi.org/10.1002/edm2.163.
  8. Malik, A., Waseem Amjad, Faisal Inayat, M. Nadeem, S. Weissman, Muhammad Imran Malik, Ans Ahmad Jajja, Ahmad Masood Khan, and James H. Tabibian. 2022. “The Effects of Liraglutide on Liver Enzymes and Metabolic Factors in Patients with Nonalcoholic Steatohepatitis: A Meta-Analysis of Randomized Controlled Trials.” Przegla̜d Gastroenterologiczny. https://doi.org/10.5114/pg.2022.112775.
  9. Mantovani, A., Graziana Petracca, Giorgia Beatrice, A. Csermely, A. Lonardo, and G. Targher. 2021. “Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials.” Metabolites. https://doi.org/10.3390/metabo11020073.
  10. Mantovani, A., and G. Targher. 2021. “Glucagon-like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Steatohepatitis: New Insights from Subcutaneous Semaglutide.” Hepatobiliary Surgery and Nutrition. https://doi.org/10.21037/hbsn-2021-13.
  11. Mosenzon, Ofri, Meir Schechter, and G. Leibowitz. 2021. “Kidney Outcomes With Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes.” Advances in Chronic Kidney Disease. https://doi.org/10.1053/j.ackd.2021.04.005.
  12. Nørgaard, C. H., Sarah Friedrich, C. T. Hansen, T. Gerds, C. Ballard, D. Møller, L. B. Knudsen, et al. 2022. “Treatment with Glucagon‐like Peptide‐1 Receptor Agonists and Incidence of Dementia: Data from Pooled Double‐blind Randomized Controlled Trials and Nationwide Disease and Prescription Registers.” Alzheimer’s & Dementia : Translational Research & Clinical Interventions. https://doi.org/10.1002/trc2.12268.
  13. Toimil, A. Rojano, and A. Ciudin. 2021. “GLP-1 Receptor Agonists in Diabetic Kidney Disease: From Physiology to Clinical Outcomes.” J. Clin. Med. 2021, 10(17), https://www.mdpi.com/2077-0383/10/17/3955
  14. Austin J, Marks D. Hormonal regulators of appetite. Int J Pediatr Endocrinol. 2009;2009:141753. doi: 10.1155/2009/141753. Epub 2008 Dec 3. PMID: 19946401; PMCID: PMC2777281. https://pmc.ncbi.nlm.nih.gov/articles/PMC2777281/

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