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Young, Katherine G.; McInnes, Eram Haider; Massey, Robert J.; Kahkoska, Anna R.; Pilla, Scott J.; Raghavan, Sridharan; Stanislawski, Maggie A.; Tobias, Deirdre K.; McGovern, Andrew P.; Dawed, Adem Y.; Jones, Angus G.; Pearson, Ewan R.; Dennis, John M.; Tobias, Deirdre K.; Merino, Jordi; Ahmad, Abrar; Aiken, Catherine; Benham, Jamie L.; Bodhini, Dhanasekaran; Clark, Amy L.; Colclough, Kevin; Corcoy, Rosa; Cromer, Sara J.; Duan, Daisy; [...]

Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review

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  • Media type: E-Article
  • Title: Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review
  • Contributor: Young, Katherine G.; McInnes, Eram Haider; Massey, Robert J.; Kahkoska, Anna R.; Pilla, Scott J.; Raghavan, Sridharan; Stanislawski, Maggie A.; Tobias, Deirdre K.; McGovern, Andrew P.; Dawed, Adem Y.; Jones, Angus G.; Pearson, Ewan R.; Dennis, John M.; Tobias, Deirdre K.; Merino, Jordi; Ahmad, Abrar; Aiken, Catherine; Benham, Jamie L.; Bodhini, Dhanasekaran; Clark, Amy L.; Colclough, Kevin; Corcoy, Rosa; Cromer, Sara J.; Duan, Daisy; [...]
  • imprint: Springer Science and Business Media LLC, 2023
  • Published in: Communications Medicine
  • Language: English
  • DOI: 10.1038/s43856-023-00359-w
  • ISSN: 2730-664X
  • Keywords: General Medicine
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.</jats:p> </jats:sec>
  • Access State: Open Access