SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes: a clinical practice guideline

Abstract

Clinical question What are the benefits and harms of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists when added to usual care (lifestyle interventions and/or other diabetes drugs) in adults with type 2 diabetes at different risk for cardiovascular and kidney outcomes? Current practice Clinical decisions about treatment of type 2 diabetes have been led by glycaemic control for decades. SGLT-2 inhibitors and GLP-1 receptor agonists are traditionally used in people with elevated glucose level after metformin treatment. This has changed through trials demonstrating atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) benefits independent of medications’ glucose-lowering potential. Recommendations The guideline panel issued risk-stratified recommendations concerning the use of SGLT-2 inhibitors or GLP-1 receptor agonists in adults with type 2 diabetes • Three or fewer cardiovascular risk factors without established CVD or CKD: Weak recommendation against starting SGLT-2 inhibitors or GLP-1 receptor agonists. • More than three cardiovascular risk factors without established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and weak against starting GLP-1 receptor agonists. • Established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and GLP-1 receptor agonists. • Established CVD and CKD: Strong recommendation for starting SGLT-2 inhibitors and weak recommendation for starting GLP-1 receptor agonists. • For those committed to further reducing their risk for CVD and CKD outcomes: Weak recommendation for starting SGLT-2 inhibitors rather than GLP-1 receptor agonists. How this guideline was created An international panel including patients, clinicians, and methodologists created these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel applied an individual patient perspective. The evidence A linked systematic review and network meta-analysis (764 randomised trials included 421 346 participants) of benefits and harms found that SGLT-2 inhibitors and GLP-1 receptor agonists generally reduce overall death, and incidence of myocardial infarctions, and end-stage kidney disease or kidney failure (moderate to high certainty evidence). These medications exert different effects on stroke, hospitalisations for heart failure, and key adverse events in different subgroups. Absolute effects of benefit varied widely based on patients’ individual risk (for example, from five fewer deaths in the lowest risk to 48 fewer deaths in the highest risk, for 1000 patients treated over five years). A prognosis review identified 14 eligible risk prediction models, one of which (RECODe) informed most baseline risk estimates in evidence summaries to underpin the risk-stratified recommendations. Concerning patients’ values and preferences, the recommendations were supported by evidence from a systematic review of published literature, a patient focus group study, a practical issues summary, and a guideline panel survey. Understanding the recommendation We stratified the recommendations by the levels of risk for CVD and CKD and systematically considered the balance of benefits, harms, other considerations, and practical issues for each risk group. The strong recommendation for SGLT-2 inhibitors in patients with CVD and CKD reflects what the panel considered to be a clear benefit. For all other adults with type 2 diabetes, the weak recommendations reflect what the panel considered to be a finer balance between benefits, harms, and burdens of treatment options. Clinicians using the guideline can identify their patient’s individual risk for cardiovascular and kidney outcomes using credible risk calculators such as RECODe. Interactive evidence summaries and decision aids may support well informed treatment choices, including shared decision making.

Safety and Efficacy of SGLT2 Inhibitors: A Multiple-Treatment Meta-Analysis of Clinical Decision Indicators

“…In this sense, the first conclusion of the analysis of Figure 5 is that ertugliflozin is a less beneficial drug than the other three SGLT2i. The second conclusion, based on the data of the network meta-analysis ( Table S4 ) and rankograms ( Figure 6 ), along with the pairwise SGLT2i versus placebo comparisons ( Figure 3 ), is that our data, together, reinforce the most accepted current recommendations [ 42 , 43 ] on the management of T2DM in patients with or at risk of atherosclerotic CVD, but exclude ertugliflozin based on these recommendations. Moreover, it can be stated that, in light of the available evidence about risks and benefits, empagliflozin is the SGLT2i most advisable for patients with T2DM who are at high cardiovascular risk.…”

Effect of SGLT2-Inhibitors on Epicardial Adipose Tissue: A Meta-Analysis

“…For decades, clinical decisions about the treatment of T2D have been based on glycemic control. This has changed due to trials demonstrating atherosclerotic cardiovascular disease and chronic kidney disease benefits independent of the glucose-lowering potential of medications [39]. The SGLT2 inhibitor has been recognized as one of the front-line treatment drugs by the new guidelines for the management of T2D [40,41].…”

Newer drug treatments for type 2 diabetes

“…13 -15 Now an international panel of clinicians, methodologists, and patient partners seek to address these limitations through development of practical guidelines on the use of SGLT-2 inhibitors and GLP-1 receptor agonists for patients with type 2 diabetes. 16 The central approach is risk based, with recommendations for both drug classes in four patient categories: (a) those without established cardiovascular or chronic kidney disease and three or fewer cardiovascular risk factors, (b) those without established disease but with more than three risk factors, (c) those with either cardiovascular disease or chronic kidney disease, and (d) those with both cardiovascular and chronic kidney disease. A fifth recommendation centres on the preferences for SGLT-2 inhibitors or GLP-1 receptor agonists for patients committed to further reducing their risk for cardiovascular and kidney disease.…”