An international panel of clinicians, methodologists and patients used the findings of a linked systematic review and network meta-analysis to devise risk-stratified guidance on the use of SGLT2 inhibitors and GLP-1 agonists in five patient categories.
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In addition to a systematic review of patient values and preferences, the guidance was informed by a patient focus group study, a practical issues summary, and a guideline panel survey.
The guidance, published in the BMJ, recommends SGLT2 inhibitors for all but the lowest risk group of patients, for whom there is no clear benefit but potential risks (eg, genital infections). GLP-1 agonists are recommended only for those with cardiovascular disease (CVD), chronic kidney disease (CKD), or both, though there is a preference for SGLT2 inhibitors in such patients.
'This guideline represents a shift from the traditional focus on glycaemic control to a focus on the absolute reduction of cardiovascular and kidney disease outcomes,' say the authors.
The panel issued the following recommendations:
- For patients with three or fewer cardiovascular risk factors without established CVD or CKD: weak recommendation against starting SGLT2 inhibitors or GLP-1 receptor agonists.
- For patients with more than three cardiovascular risk factors without established CVD or CKD: weak recommendation for starting SGLT2 inhibitors and weak against starting GLP-1 receptor agonists.
- For patients with established CVD or CKD: weak recommendation for starting SGLT2 inhibitors and GLP-1 receptor agonists.
- For patients with established CVD and CKD: strong recommendation for starting SGLT2 inhibitors and weak recommendation for starting GLP-1 receptor agonists.
- For patients committed to further reducing their risk of CVD and CKD outcomes: weak recommendation for starting SGLT2 inhibitors rather than GLP-1 receptor agonists.
The authors say their 'strong' recommendation for SGLT2 inhibitors in patients with CVD and CKD reflects 'a clear benefit'. For all other adults with type II diabetes, they say the 'weak' recommendations reflect 'a finer balance between benefits, harms, and burdens of treatment options'.
A linked editorial notes that the recommendations are broadly similar to recently updated guidelines for patients with established cardiovascular or chronic kidney disease, but the recommendation to use SGLT2 inhibitors for patients with multiple risk factors has not been widely adopted by other guidelines. The editorial's authors hail the involvement of patients in development of the recommendations, which they say no existing guidance has reported.
The editorial cautions that the guidance focuses on cardiorenal outcomes and not microvascular outcomes or quality of life, or the benefits of measures such as lifestyle modification and cardiovascular risk management. In addition, says the editorial, the guidance does not consider selection of individual drugs within each of the two therapeutic classes, although evidence suggests possible variation in benefits and risks.