Experts Advise SGLT-2, GLP-1 Drugs for At-Risk Adults

BMJ Group

SGLT-2 inhibitor and GLP-1 receptor agonist drugs should be used in all or almost all adults with type 2 diabetes at higher risk of cardiovascular and kidney complications, and in the majority of adults at moderate risk of complications, say a panel of international experts in The BMJ today.

But for those at lower risk, they advise against routinely recommending these drugs, and suggest doctors discuss treatment options with their patients, noting that decisions are likely to be more contextual and based on what's most important to the individual.

For adults with diabetes and chronic kidney disease at higher risk of complications, they suggest using the drug finerenone as benefits are more likely to outweigh the risks, but they suggest against using finerenone for those at moderate risk of complications.

For adults with diabetes and obesity, they emphasise the importance of weight loss alongside cardiovascular and kidney risk reduction and suggest use of tirzepatide, irrespective of the patient's risk of cardiovascular and kidney complications, given its superior effects on weight loss.

However, they note that when choosing between GLP-1 receptor agonists and tirzepatide, clinicians should weigh the higher certainty of cardiovascular and kidney benefits (offered by GLP-1 receptor agonists) against larger weight loss benefits (offered by tirzepatide) based on a patient's risk profile as well as their values and preferences.

And for adults at higher risk of cardiovascular and kidney complications, they acknowledge that tirzepatide should generally not replace drugs that are effective in reducing these risks. For example, if a GLP-1 receptor agonist is replaced, other drugs that reduce these risks should be initiated or continued.

This living practice guideline is based on the latest evidence and is part of The BMJ's 'Rapid Recommendations' initiative - to produce rapid and trustworthy guidance based on new evidence to help doctors make better decisions with their patients.

The guideline uses the GRADE approach to assess the quality of evidence and make structured trustworthy recommendations and is accompanied by an interactive decision aid (MATCH-IT) to help inform shared decision-making.

The recommendations are based on a living systematic review and network meta-analysis of evidence from nearly half a million adults with type 2 diabetes across 869 randomised controlled trials, covering 63 medications and 26 outcomes identified as important to patients.

The panel recognises that the lack of availability or high costs of some medications may be prohibitive and will impact on how these recommendations are implemented across different health care systems.

* "All countries struggle to keep up to date with all these drugs and studies coming out. The record-large systematic review that informs these guidelines illustrate why global collaboration on living evidence is needed to inform policy and practice, like we did for COVID-19 " says senior author professor Per Olav Vandvik.

Therefore, the authors encourage re-use, adaptation and translation of these living guidelines through global initiatives such as the Alliance for Living Evidence (ALIVE) and the Evidence Synthesis Infrastructure Collaborative (ESIC) . The panel also commits to regular updates to recommendations in parallel with evidence updates as new information becomes available to support policy and practice worldwide.

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