In T2D, SGLT-2 inhibitor effects on CV and kidney outcomes were consistent regardless of GLP-1 receptor agonist use
The number of patients who received combination therapy with an SGLT-2 inhibitor and a GLP-1 receptor agonist in a recent review was too small to guide practice, but it's likely that more patients will soon be on this regimen, an ACP Journal Club commentary said.
A review found that sodium-glucose cotransporter-2 (SGLT-2) inhibitors similarly improved outcomes regardless of whether patients are also taking a glucagon-like peptide-1 (GLP-1) receptor agonist. It included 12 randomized, double-blind, placebo-controlled trials in which 4.2% of participants with type 2 diabetes (T2D) were using GLP-1 receptor agonists at baseline. SGLT-2 inhibitors reduced the risk of major adverse cardiovascular (CV) events, hospitalizations for heart failure (HF) or CV death, and chronic kidney disease (CKD) progression.
The study was published in the August issue of The Lancet Diabetes & Endocrinology. The following commentary by Michelle Maher, MB BCh BAO, and Sean Dinneen, MD, was published in the ACP Journal Club section of Annals of Internal Medicine on Nov. 5.
SGLT-2 inhibitors have been shown to reduce CV events in patients with T2D and CV events and hospital admissions in patients with HF, and they are associated with improved outcomes in patients with CKD—with or without diabetes. They are included in guidelines for treatment of T2D, HF (both preserved and reduced ejection fraction), and CKD. The meta-analysis by Apperloo and colleagues provides strong evidence of the benefits of SGLT-2 inhibitors on hard clinical outcomes across a spectrum of trials of patients with cardio-renal metabolic disorders.
The main question addressed by the meta-analysis is whether the benefits of SGLT-2 inhibitor therapy are influenced by concomitant use of GLP-1 receptor agonists, a class of drug also associated with improved outcomes in patients with cardio-renal metabolic disease. Despite large overall numbers of patients in the analysis, ≤5% were treated with combined SGLT-2 inhibitor and a GLP-1 receptor agonist therapy—too few to draw meaningful conclusions to guide practicing clinicians.
Combined use of SGLT-2 inhibitors and GLP-1 receptor agonists is likely to increase given the evidence for organ protection and guideline recommendations. Combination treatment may be indicated in high-risk patients with CV disease or CKD, but shared decision making is paramount to contextualize the evidence in terms of benefits versus safety. It is conceivable that adverse events such as hypoglycemia may be more common when the treatments are combined. Barriers to combined use include cost in many jurisdictions; cost-effectiveness remains unclear, but economic evaluation has potential to support their use.