Clinical Question

Which patients with type 2 diabetes mellitus should have sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists added to their treatment to prevent adverse cardiovascular or kidney outcomes?

Bottom Line

The guidelines give clear guidance on selecting an SGLT2 inhibitor, a GLP-1 receptor agonist, or neither in patients with type 2 diabetes. The guidelines are a bit conservative to some, but guideline development is a two-step process: determining the evidence and then weighing the value based on benefits and risks. (Level of Evidence = 5)

Synopsis

When selecting a treatment for a patient, three questions should be asked: Does it work? How well does it work? Which patients does it work for? The guideline, based on a systematic review and network meta-analysis of 764 randomized trials with more than 400,000 patients, set out to provide guidance based on these questions. The review found that SGLT2 inhibitors and GLP-1 receptor agonists, on average and with a moderate to high certainty of evidence, reduce overall death, incidence of myocardial infarction, and incidence of end-stage kidney disease or renal failure, with effects on other outcomes in different subgroups. The absolute benefit ranged from five to 48 fewer deaths per 1,000 patients treated for five years, based on baseline risk. A group of clinicians, methodologists, and patients came up with the following recommendations for patients with type 2 diabetes who have cardiovascular disease (CVD), chronic kidney disease (CKD), or cardiovascular risk factors:

• Established CVD and CKD: start an SGLT2 inhibitor (strong recommendation) or consider a GLP-1 receptor agonist (weak recommendation)

• Established CVD or CKD: consider an SGLT2 inhibitor or GLP-1 receptor agonist (weak recommendation)

• Four or more cardiovascular risk factors, but no CVD or CKD: consider SGLT2 inhibitor (weak recommendation), but not a GLP-1 receptor agonist (weak recommendation against)

• Three or fewer cardiovascular risk factors: do not start an SGLT2 inhibitor or GLP-1 receptor agonist (weak recommendation against)

The guideline focuses on patient-oriented outcomes and provides clear and actionable advice. Its development included stakeholders and a methodologist and was based on a systematic review. One caveat is that race and ethnicity are listed as a cardiovascular risk factor, which warrants careful consideration and shared decision-making regarding how this should affect treatment decisions.

Study design: Practice guideline

Funding source: Foundation

Setting: Outpatient (any)

Reference: Li S, Vandvik PO, Lytvyn L, et al. SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes: a clinical practice guideline. BMJ. 2021;373:n1091.

Editor's Note: Dr. Shaughnessy is an assistant medical editor for AFP.