Your cart is currently empty!
Mapping the effectiveness and risks of GLP-1 receptor agonists
Pfeffer, M. A. et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N. Engl. J. Med. 373, 2247–2257 (2015).
Marso, S. P. et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375, 311–322 (2016).
Marso, S. P. et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 375, 1834–1844 (2016).
Husain, M. et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 381, 841–851 (2019).
Holman, R. R. et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 377, 1228–1239 (2017).
Hernandez, A. F. et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 392, 1519–1529 (2018).
Gerstein, H. C. et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 394, 121–130 (2019).
Gerstein, H. C. et al. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. N. Engl. J. Med. 385, 896–907 (2021).
Perkovic, V. et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N. Engl. J. Med. 391, 109–121 (2024).
Kosiborod, M. N. et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N. Engl. J. Med. 389, 1069–1084 (2023).
Gerstein, H. C. et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet 394, 131–138 (2019).
Mann, J. F. E. et al. Liraglutide and renal outcomes in type 2 diabetes. N. Engl. J. Med. 377, 839–848 (2017).
Muskiet, M. H. A. et al. Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 6, 859–869 (2018).
Tuttle, K. R. et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 6, 605–617 (2018).
Wilding, J. P. H. et al. Once-weekly semaglutide in adults with overweight or obesity. N. Engl. J. Med. 384, 989–1002 (2021).
Jastreboff, A. M. et al. Tirzepatide once weekly for the treatment of obesity. N. Engl. J. Med. 387, 205–216 (2022).
Kelly, A. S. et al. A randomized, controlled trial of liraglutide for adolescents with obesity. N. Engl. J. Med. 382, 2117–2128 (2020).
Wharton, S. et al. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. N. Engl. J. Med. 389, 877–888 (2023).
Watanabe, J. H., Kwon, J., Nan, B. & Reikes, A. Trends in glucagon-like peptide 1 receptor agonist use, 2014 to 2022. J. Am. Pharm. Assoc. 64, 133–138 (2024).
Hegland, T.A., Fang, Z. & Bucher, K. GLP-1 medication use for type 2 diabetes has soared.JAMA 332, 952–953 (2024).
Sodhi, M., Rezaeianzadeh, R., Kezouh, A. & Etminan, M. Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss. JAMA 330, 1795–1797 (2023).
Vidal, J., Flores, L., Jiménez, A., Pané, A. & de Hollanda, A. What is the evidence regarding the safety of new obesity pharmacotherapies. Int. J. Obes. https://doi.org/10.1038/s41366-024-01488-5 (2024).
Wang, W. et al. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Nat. Med. 30, 168–176 (2024).
Laurindo, L. F. et al. GLP-1a: going beyond traditional use. Int. J. Mol. Sci. 23, 739 (2022).
Rubin, R. Could GLP-1 receptor agonists like semaglutide treat addiction, Alzheimer disease, and other conditions? JAMA 331, 1519–1521 (2024).
Wang, W. et al. Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. Nat. Commun. 15, 4548 (2024).
Wang, W. et al. Association of semaglutide with tobacco use disorder in patients with type 2 diabetes: target trial emulation using real-world data. Ann. Intern. Med. 177, 1016–1027 (2024).
Drucker, D. J. The benefits of GLP-1 drugs beyond obesity. Science 385, 258–260 (2024).
Lenharo, M. Why do obesity drugs seem to treat so many other ailments? Nature 633, 758–760 (2024).
Al-Aly, Z., Xie, Y. & Bowe, B. High-dimensional characterization of post-acute sequelae of COVID-19. Nature 594, 259–264 (2021).
Leggio, L. et al. GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders. Nat. Med. 29, 2993–2995 (2023).
Wium-Andersen, I. K. et al. Use of GLP-1 receptor agonists and subsequent risk of alcohol-related events. A nationwide register-based cohort and self-controlled case series study. Basic Clin. Pharmacol. Toxicol. 131, 372–379 (2022).
Klausen, M. K. et al. Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight 7, e159863 (2022).
Yammine, L., Balderas, J. C., Weaver, M. F. & Schmitz, J. M. Feasibility of exenatide, a GLP-1R agonist, for treating cocaine use disorder: a case series study. J. Addict. Med. 17, 481–484 (2023).
Angarita, G. A. et al. Testing the effects of the GLP-1 receptor agonist exenatide on cocaine self-administration and subjective responses in humans with cocaine use disorder. Drug Alcohol Depend. 221, 108614 (2021).
Dixit, T. S., Sharma, A. N., Lucot, J. B. & Elased, K. M. Antipsychotic-like effect of GLP-1 agonist liraglutide but not DPP-IV inhibitor sitagliptin in mouse model for psychosis. Physiol. Behav. 114−115, 38–41 (2013).
Gunturu, S. The potential role of GLP-1 agonists in psychiatric disorders: a paradigm shift in mental health treatment. Indian J. Psychol. Med. 46, 193–195 (2024).
López-Ojeda, W. & Hurley, R. A. Glucagon-like peptide 1: an introduction and possible implications for neuropsychiatry. J. Neuropsychiatry Clin. Neurosci. 36, A4–A86 (2024).
Flintoff, J., Kesby, J. P., Siskind, D. & Burne, T. H. J. Treating cognitive impairment in schizophrenia with GLP-1RAs: an overview of their therapeutic potential. Expert Opin. Investig. Drugs 30, 877–891 (2021).
European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 8−11 April 2024. https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-8-11-april-2024 (12 April 2024).
Du, H., Meng, X., Yao, Y. & Xu, J. The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer’s disease. Front. Endocrinol. 13, 1033479 (2022).
Mehan, S. et al. Potential roles of glucagon-like peptide-1 and its analogues in dementia targeting impaired insulin secretion and neurodegeneration. Degener. Neurol. Neuromuscul. Dis. 12, 31–59 (2022).
Colin, I. M., Szczepanski, L. W., Gérard, A. C. & Elosegi, J. A. Emerging evidence for the use of antidiabetic drugs, glucagon-like peptide 1 receptor agonists, for the treatment of Alzheimer’s disease. touchREV. Endocrinol. 19, 16–24 (2023).
Lenharo, M. Obesity drugs have another superpower: taming inflammation. Nature 626, 246 (2024).
Nørgaard, C. H. et al. 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 Dement. 8, e12268 (2022).
De Giorgi, R. et al. 12-month neurological and psychiatric outcomes of semaglutide use for type 2 diabetes: a propensity-score matched cohort study. eClinicalMedicine 74, 102726 (2024).
Atri, A. et al. evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating the neuroprotective effects of semaglutide in early Alzheimer’s disease. Alzheimer’s Dement. 18, e062415 (2022).
Manavi, M. A. Neuroprotective effects of glucagon-like peptide-1 (GLP-1) analogues in epilepsy and associated comorbidities. Neuropeptides 94, 102250 (2022).
Wang, L. et al. Semaglutide attenuates seizure severity and ameliorates cognitive dysfunction by blocking the NLR family pyrin domain containing 3 inflammasome in pentylenetetrazole‑kindled mice. Int. J. Mol. Med. 48, 219 (2021).
Hussein, A. M. et al. Effects of GLP-1 receptor activation on a pentylenetetrazole−kindling rat model. Brain Sci. 9, 108 (2019).
Liu, S. et al. The glucagon-like peptide-1 analogue liraglutide reduces seizures susceptibility, cognition dysfunction and neuronal apoptosis in a mouse model of Dravet syndrome. Front. Pharmacol. 11, 136 (2020).
Sattar, N. et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 9, 653–662 (2021).
Jia, G., Aroor, A. R. & Sowers, J. R. Glucagon-like peptide 1 receptor activation and platelet function: beyond glycemic control. Diabetes 65, 1487–1489 (2016).
Drucker, D. J. The cardiovascular biology of glucagon-like peptide-1. Cell Metab. 24, 15–30 (2016).
Sternkopf, M. et al. Native, intact glucagon-like peptide 1 is a natural suppressor of thrombus growth under physiological flow conditions. Arter. Thromb. Vasc. Biol. 40, e65–e77 (2020).
Steven, S. et al. Glucagon-like peptide-1 receptor signalling reduces microvascular thrombosis, nitro-oxidative stress and platelet activation in endotoxaemic mice. Br. J. Pharmacol. 174, 1620–1632 (2017).
Cameron-Vendrig, A. et al. Glucagon-like peptide 1 receptor activation attenuates platelet aggregation and thrombosis. Diabetes 65, 1714–1723 (2016).
Zhang, Y., Chen, R., Jia, Y., Chen, M. & Shuai, Z. Effects of exenatide on coagulation and platelet aggregation in patients with type 2 diabetes. Drug Des. Devel. Ther. 15, 3027–3040 (2021).
Horvei, L. D., Brækkan, S. K. & Hansen, J. B. Weight change and risk of venous thromboembolism: the Tromsø study. PLoS ONE 11, e0168878 (2016).
de Lemos, J. A. et al. Tirzepatide reduces 24-hour ambulatory blood pressure in adults with body mass index ≥27 kg/m2: SURMOUNT-1 Ambulatory Blood Pressure Monitoring Substudy. Hypertension 81, e41–e43 (2024).
Goodwill, A. G. et al. Cardiovascular and hemodynamic effects of glucagon-like peptide-1. Rev. Endocr. Metab. Disord. 15, 209–217 (2014).
Ribeiro-Silva, J. C., Tavares, C. A. M. & Girardi, A. C. C. The blood pressure lowering effects of glucagon-like peptide-1 receptor agonists: a mini-review of the potential mechanisms. Curr. Opin. Pharmacol. 69, 102355 (2023).
Goud, A., Zhong, J., Peters, M., Brook, R. D. & Rajagopalan, S. GLP-1 agonists and blood pressure: a review of the evidence. Curr. Hypertens. Rep. 18, 16 (2016).
Yang, F. et al. GLP-1 receptor: a new target for sepsis. Front. Pharmacol. 12, 706908 (2021).
Helmstädter, J. et al. GLP-1 analog liraglutide improves vascular function in polymicrobial sepsis by reduction of oxidative stress and inflammation. Antioxidants 10, 1175 (2021).
Yi, H. et al. Activation of glucagon-like peptide-1 receptor in microglia exerts protective effects against sepsis-induced encephalopathy via attenuating endoplasmic reticulum stress-associated inflammation and apoptosis in a mouse model of sepsis. Exp. Neurol. 363, 114348 (2023).
Scirica, B. et al. The effect of semaglutide on mortality and COVID-19–related deaths.JACC 84, 1632–1642 (2024).
Wang, L., Xu, R., Kaelber, D. C. & Berger, N. A. Glucagon-like peptide 1 receptor agonists and 13 obesity-associated cancers in patients with type 2 diabetes. JAMA Netw. Open 7, e2421305 (2024).
Yu, M. et al. The relationship between the use of GLP-1 receptor agonists and the incidence of respiratory illness: a meta-analysis of randomized controlled trials. Diabetol. Metab. Syndr. 15, 164 (2023).
Altintas Dogan, A. D. et al. Respiratory effects of treatment with a glucagon-like peptide-1 receptor agonist in patients suffering from obesity and chronic obstructive pulmonary disease. Int. J. Chron. Obstruct. Pulmon. Dis. 17, 405–414 (2022).
Foer, D. et al. Association of GLP-1 receptor agonists with chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes. Am. J. Respir. Crit. Care Med. 208, 1088–1100 (2023).
Pradhan, R. et al. Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study. BMJ 379, e071380 (2022).
Yeo, Y.H. et al. Increased risk of aspiration pneumonia associated with endoscopic procedures among patients with glucagon-like peptide 1 receptor agonist use.Gastroenterology 167, 402–404 (2024).
Dixit, A. A., Bateman, B. T., Hawn, M. T., Odden, M. C. & Sun, E. C. Preoperative GLP-1 receptor agonist use and risk of postoperative respiratory complications. JAMA 331, 1672–1673 (2024).
Wang, W. et al. The role of glucagon-like peptide-1 receptor agonists in chronic obstructive pulmonary disease. Int. J. Chron. Obstruct. Pulmon. Dis. 18, 129–137 (2023).
Langenberg, C., Hingorani, A. D. & Whitty, C. J. M. Biological and functional multimorbidity—from mechanisms to management. Nat. Med. 29, 1649–1657 (2023).
Xie, Y., Choi, T. & Al-Aly, Z. Postacute sequelae of SARS-CoV-2 infection in the pre-Delta, Delta, and Omicron eras. N. Engl. J. Med. 391, 515–525 (2024).
Cai, M., Xie, Y., Topol, E. J. & Al-Aly, Z. Three-year outcomes of post-acute sequelae of COVID-19. Nat. Med. 30, 1564–1573 (2024).
Bowe, B., Xie, Y. & Al-Aly, Z. Postacute sequelae of COVID-19 at 2 years. Nat. Med. 29, 2347–2357 (2023).
Xu, E., Xie, Y. & Al-Aly, Z. Long-term gastrointestinal outcomes of COVID-19. Nat. Commun. 14, 983 (2023).
Xu, E., Xie, Y. & Al-Aly, Z. Risks and burdens of incident dyslipidaemia in long COVID: a cohort study. Lancet Diabetes Endocrinol. 11, 120–128 (2023).
Xie, Y., Choi, T. & Al-Aly, Z. Long-term outcomes following hospital admission for COVID-19 versus seasonal influenza: a cohort study. Lancet Infect. Dis. 24, 239–255 (2024).
Al-Aly, Z. & Topol, E. Solving the puzzle of long Covid. Science 383, 830–832 (2024).
Al-Aly, Z. et al. Long COVID science, research and policy. Nat. Med. 30, 2148–2164 (2024).
Xie, Y. et al. Proton pump inhibitors and risk of incident CKD and progression to ESRD. J. Am. Soc. Nephrol. 27, 3153–3163 (2016).
Xie, Y. et al. Risk of death among users of proton pump inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open 7, e015735 (2017).
Xie, Y. et al. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int. 91, 1482–1494 (2017).
Xie, Y. et al. Higher blood urea nitrogen is associated with increased risk of incident diabetes mellitus. Kidney Int. 93, 741–752 (2018).
Maynard, C. Ascertaining veterans’ vital status: VA data sources for mortality ascertainment and cause of death. https://www.hsrd.research.va.gov/for_researchers/cyber_seminars/archives/3783-notes.pdf (2017).
Cai, M. et al. Temporal trends in incidence rates of lower extremity amputation and associated risk factors among patients using Veterans Health Administration services from 2008 to 2018. JAMA Netw. Open 4, e2033953 (2021).
Xie, Y. et al. Comparative effectiveness of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and sulfonylureas on risk of major adverse cardiovascular events: emulation of a randomised target trial using electronic health records. Lancet Diabetes Endocrinol. 11, 644–656 (2023).
Xie, Y. et al. Clinical implications of estimated glomerular filtration rate dip following sodium−glucose cotransporter-2 inhibitor initiation on cardiovascular and kidney outcomes. J. Am. Heart Assoc. 10, e020237 (2021).
Xie, Y. et al. Comparative effectiveness of sodium−glucose cotransporter 2 inhibitors vs sulfonylureas in patients with type 2 diabetes. JAMA Intern. Med. 181, 1043–1053 (2021).
Xie, Y. et al. Comparative effectiveness of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and sulfonylureas on risk of kidney outcomes: emulation of a target trial using health care databases. Diabetes Care 43, 2859–2869 (2020).
Xie, Y. et al. Comparative effectiveness of the sodium−glucose cotransporter 2 inhibitor empagliflozin versus other antihyperglycemics on risk of major adverse kidney events. Diabetes Care 43, 2785–2795 (2020).
Xie, Y., Choi, T. & Al-Aly, Z. Nirmatrelvir and the risk of post-acute sequelae of COVID-19.JAMA Intern. Med. 183, 554–564 (2023).
Xie, Y., Bowe, B. & Al-Aly, Z. Nirmatrelvir and risk of hospital admission or death in adults with Covid-19: emulation of a randomized target trial using electronic health records. BMJ 381, e073312 (2023).
Xie, Y., Bowe, B. & Al-Aly, Z. Molnupiravir and risk of hospital admission or death in adults with Covid-19: emulation of a randomized target trial using electronic health records. BMJ 380, e072705 (2023).
Xie, Y., Choi, T. & Al-Aly, Z. Molnupiravir and risk of post-acute sequelae of Covid-19: cohort study. BMJ 381, e074572 (2023).
van Buuren, S. Multiple imputation of discrete and continuous data by fully conditional specification. Stat. Methods Med. Res. 16, 219–242 (2007).
Harrell, F. E. Regression Modeling Strategies: With Applications to Linear Models, Logistic and Ordinal Regression, and Survival Analysis (Springer, 2015).
Schneeweiss, S. Automated data-adaptive analytics for electronic healthcare data to study causal treatment effects. Clin. Epidemiol. 10, 771–788 (2018).
Schneeweiss, S. et al. High-dimensional propensity score adjustment in studies of treatment effects using health care claims data. Epidemiology 20, 512–522 (2009).
Austin, P. C. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity‐score matched samples. Stat. Med. 28, 3083–3107 (2009).
Crump, R. K., Hotz, V. J., Imbens, G. W. & Mitnik, O. A. Dealing with limited overlap in estimation of average treatment effects. Biometrika 96, 187–199 (2009).
Hernan, M. A. & Robins, J. M. Causal Inference: What If (CRC Press, 2010).
Uno, H. et al. Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis. J. Clin. Oncol. 32, 2380–2385 (2014).
Andersen, P. K., Hansen, M. G. & Klein, J. P. Regression analysis of restricted mean survival time based on pseudo-observations. Lifetime Data Anal. 10, 335–350 (2004).
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57, 289–300 (1995).
GLP-1 receptor agonists are a class of medications commonly used to treat type 2 diabetes by stimulating insulin production and reducing blood sugar levels. However, like any medication, there are potential risks and side effects associated with their use.
In this post, we will explore the effectiveness of GLP-1 receptor agonists in managing type 2 diabetes, as well as the potential risks and side effects that patients should be aware of.
Effectiveness of GLP-1 receptor agonists:
Studies have shown that GLP-1 receptor agonists are highly effective in lowering blood sugar levels in patients with type 2 diabetes. They work by stimulating the release of insulin from the pancreas, slowing down digestion, and reducing the production of glucose in the liver.
In addition to lowering blood sugar levels, GLP-1 receptor agonists have also been shown to promote weight loss in patients with type 2 diabetes. This is because they can reduce appetite and increase feelings of fullness, leading to a decrease in caloric intake.
Risks and side effects of GLP-1 receptor agonists:
While GLP-1 receptor agonists are generally well-tolerated, there are some potential risks and side effects that patients should be aware of. These can include:
– Nausea and vomiting
– Diarrhea
– Hypoglycemia (low blood sugar)
– Pancreatitis
– Thyroid tumors
– Allergic reactions
It’s important for patients to discuss the potential risks and benefits of GLP-1 receptor agonists with their healthcare provider before starting treatment. Additionally, patients should be monitored regularly for any signs of side effects or complications.
Overall, GLP-1 receptor agonists are a valuable treatment option for patients with type 2 diabetes, but it’s important to weigh the potential risks and benefits before starting treatment. By mapping out the effectiveness and risks of these medications, patients can make informed decisions about their diabetes management.
Tags:
- GLP-1 receptor agonists
- Effectiveness of GLP-1 receptor agonists
- Risks of GLP-1 receptor agonists
- GLP-1 agonist benefits
- GLP-1 receptor agonist safety
- GLP-1 agonist side effects
- GLP-1 agonist risk assessment
- GLP-1 receptor agonist efficacy
- GLP-1 agonist comparison
- GLP-1 agonist research findings
#Mapping #effectiveness #risks #GLP1 #receptor #agonists
Leave a Reply