Another Win for GLP-1 Receptor Agonists: Treatment for Patients With Diabetes and CKD

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists were once thought of as simple diabetes medications, only capable of lowering A1c. Over the last 5-7 years, the perspective shifted because it is evident that both classes of medications can drastically lower the risk of cardiovascular death and adverse cardiovascular events in patients with diabetes. SGLT2 inhibitors were also proven to be effective in patients with heart failure (HF) and chronic kidney disease (CKD), while GLP-1 agonists have demonstrated marked benefit in patients with obesity.

Nearly every clinical trial has demonstrated positive benefits with these drug classes. In this week's installment of Talking Therapeutics, we explore a new trial that evaluates the impact of GLP-1 agonists on kidney and cardiovascular endpoints in patients with diabetes and CKD.

Talking Point: Another Victory

In a new study, researchers explored the use of subcutaneous semaglutide at a dose of 1.0 mg weekly or placebo in patients with type 2 diabetes and CKD. The primary outcome was major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an eGFR of < 15 ml per minute per 1.73 m²), at least a 50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes.

Researchers found that among the 3533 participants, the risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (HR, 0.76; 95% CI, 0.66 to 0.88; P = 0.003). Results were similar for a composite of the kidney-specific components of the primary outcome (HR, 0.79; 95% CI, 0.66 to 0.94) and for death from cardiovascular causes (HR, 0.71; 95% CI, 0.56 to 0.89).

Talking Point: Clinicians Face New Decisions

Now that both SGLT2 inhibitors and GLP-1 agonists can improve cardiovascular and renal outcomes in patients with diabetes and CKD, clinicians have a choice to make. Without head-to-head data, such a choice is not one that’s evidence based. However, perhaps a patient’s comorbidities can guide therapy. Patients with co-morbid obesity would probably benefit more from a GLP-1 agonist, while those with concomitant HF would be better served by a SGLT2 inhibitor.

Data in other patient populations has shown that SGLT2 inhibitors and GLP-1 agonists can be combined to provide additive benefits. Hopefully, data for combination therapy is available soon for patients with diabetes and CKD, as these patients have an exceptionally high residual rate of adverse clinical outcomes.