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Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice
Randomized controlled trials (RCTs) have consistently shown glycemic and extra-glycemic benefits of long-acting injectable glucagon-like-peptide-1 receptor agonists (GLP-1RAs, liraglutide, albiglutide, exenatide once-weekly, dulaglutide, and semaglutide) in terms of reduction in the rates of cardiov...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665457/ https://www.ncbi.nlm.nih.gov/pubmed/33204129 http://dx.doi.org/10.2147/DMSO.S216054 |
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author | Morieri, Mario Luca Avogaro, Angelo Fadini, Gian Paolo |
author_facet | Morieri, Mario Luca Avogaro, Angelo Fadini, Gian Paolo |
author_sort | Morieri, Mario Luca |
collection | PubMed |
description | Randomized controlled trials (RCTs) have consistently shown glycemic and extra-glycemic benefits of long-acting injectable glucagon-like-peptide-1 receptor agonists (GLP-1RAs, liraglutide, albiglutide, exenatide once-weekly, dulaglutide, and semaglutide) in terms of reduction in the rates of cardiovascular events and mortality among patients with type 2 diabetes. Recently, the analyses of large datasets collecting routinely-accumulated data from clinical practice (ie, real-world studies, RWS) have provided new opportunities to complement the information obtained from RCTs. In this narrative review, we addressed clinically relevant questions that might be answered by well-conducted RWS: are subjects treated with GLP-1RAs in the “real-world” similar to those included in RCTs? Is the performance of GLP-1RA observed in the RWS (effectiveness) similar to that described in RCTs (efficacy)? Is the effectiveness similar in population of patients generally under-represented in RCTs? Are the cardiovascular benefits of GLP-1RAs confirmed in RWS? We also describe a few comparisons currently un-explored by specific RCTs, such as direct comparison between different administration strategies (eg, fixed- versus flexible-combination with basal-insulin) or between GLP-1RAs versus dipeptidyl-peptidase-4 inhibitor (DDP4i) or versus sodium/glucose cotransporter-2 inhibitors (SGLT-2i) on hard cardio-renal outcomes. Altogether, RWS provide highly informative information on treatment with GLP-1RAs. On the one side, RWS showed different clinical characteristics between subjects enrolled in RCTs versus those attending real-world clinics and receiving a GLP-1RA. On the other hand, RWS showed that GLP-1RA effectiveness is overall consistent in subgroups of patients less represented in RCTs. In addition, RWS allowed the identification of modifiable factors (eg, titration or adherence) that might guide physicians towards better GLP-1RAs use. Finally, multiple RWS reported better cardio-renal outcomes with GLP-1RAs than with DPP-4i, while initial findings from RWS described a weaker cardiovascular protection compared to SGLT-2i. Therefore, there is the need for further RWS and RCTs comparing these different classes of glucose lowering medications. |
format | Online Article Text |
id | pubmed-7665457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-76654572020-11-16 Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice Morieri, Mario Luca Avogaro, Angelo Fadini, Gian Paolo Diabetes Metab Syndr Obes Review Randomized controlled trials (RCTs) have consistently shown glycemic and extra-glycemic benefits of long-acting injectable glucagon-like-peptide-1 receptor agonists (GLP-1RAs, liraglutide, albiglutide, exenatide once-weekly, dulaglutide, and semaglutide) in terms of reduction in the rates of cardiovascular events and mortality among patients with type 2 diabetes. Recently, the analyses of large datasets collecting routinely-accumulated data from clinical practice (ie, real-world studies, RWS) have provided new opportunities to complement the information obtained from RCTs. In this narrative review, we addressed clinically relevant questions that might be answered by well-conducted RWS: are subjects treated with GLP-1RAs in the “real-world” similar to those included in RCTs? Is the performance of GLP-1RA observed in the RWS (effectiveness) similar to that described in RCTs (efficacy)? Is the effectiveness similar in population of patients generally under-represented in RCTs? Are the cardiovascular benefits of GLP-1RAs confirmed in RWS? We also describe a few comparisons currently un-explored by specific RCTs, such as direct comparison between different administration strategies (eg, fixed- versus flexible-combination with basal-insulin) or between GLP-1RAs versus dipeptidyl-peptidase-4 inhibitor (DDP4i) or versus sodium/glucose cotransporter-2 inhibitors (SGLT-2i) on hard cardio-renal outcomes. Altogether, RWS provide highly informative information on treatment with GLP-1RAs. On the one side, RWS showed different clinical characteristics between subjects enrolled in RCTs versus those attending real-world clinics and receiving a GLP-1RA. On the other hand, RWS showed that GLP-1RA effectiveness is overall consistent in subgroups of patients less represented in RCTs. In addition, RWS allowed the identification of modifiable factors (eg, titration or adherence) that might guide physicians towards better GLP-1RAs use. Finally, multiple RWS reported better cardio-renal outcomes with GLP-1RAs than with DPP-4i, while initial findings from RWS described a weaker cardiovascular protection compared to SGLT-2i. Therefore, there is the need for further RWS and RCTs comparing these different classes of glucose lowering medications. Dove 2020-11-09 /pmc/articles/PMC7665457/ /pubmed/33204129 http://dx.doi.org/10.2147/DMSO.S216054 Text en © 2020 Morieri et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Review Morieri, Mario Luca Avogaro, Angelo Fadini, Gian Paolo Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice |
title | Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice |
title_full | Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice |
title_fullStr | Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice |
title_full_unstemmed | Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice |
title_short | Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice |
title_sort | long-acting injectable glp-1 receptor agonists for the treatment of adults with type 2 diabetes: perspectives from clinical practice |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665457/ https://www.ncbi.nlm.nih.gov/pubmed/33204129 http://dx.doi.org/10.2147/DMSO.S216054 |
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