Journal article
Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review
- Abstract:
-
Background
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.
Methods
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.
Results
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.
Conclusions
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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.0MB, Terms of use)
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(Preview, Supplementary materials, pdf, 567.6KB, Terms of use)
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- Publisher copy:
- 10.1038/s43856-023-00359-w
Authors
Contributors
+ Franks, PW
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- Radcliffe Department of Medicine
- Sub department:
- RDM-Oxford Centre for Diabetes, Endocrinology and Metabolism
- Role:
- Contributor
+ Owen, KR
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- Radcliffe Department of Medicine
- Sub department:
- RDM-Oxford Centre for Diabetes, Endocrinology and Metabolism
- Role:
- Contributor
- ORCID:
- 0000-0003-3982-1407
+ Medical Research Council
More from this funder
- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MR/N00633X/1
- MR/W003988/1
- MR/K005707/1
+ National Institutes of Health
More from this funder
- Funder identifier:
- https://ror.org/01cwqze88
- Grant:
- K01HL157658
- KL2TR002490
+ British Heart Foundation
More from this funder
- Funder identifier:
- https://ror.org/02wdwnk04
- Grant:
- SP/19/6/34809
+ United States Department of Veterans Affairs
More from this funder
- Funder identifier:
- https://ror.org/05rsv9s98
- Grant:
- IK2-CX001907
+ European Foundation for the Study of Diabetes
More from this funder
- Funder identifier:
- https://ror.org/05tgz4m05
- Programme:
- Rising Star Fellowship Programme
- Publisher:
- Springer Nature
- Journal:
- communications medicine More from this journal
- Volume:
- 3
- Issue:
- 1
- Article number:
- 131
- Place of publication:
- England
- Publication date:
- 2023-10-05
- Acceptance date:
- 2023-09-15
- DOI:
- EISSN:
-
2730-664X
- Pmid:
-
37794166
- Language:
-
English
- Pubs id:
-
2033271
- Local pid:
-
pubs:2033271
- Source identifiers:
-
W4387345288
- Deposit date:
-
2026-04-02
- ARK identifier:
Terms of use
- Copyright holder:
- Young et al.
- Copyright date:
- 2023
- Rights statement:
- © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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