Cardiovascular and Kidney Benefits of Semaglutide in Type 2 Diabetes

Semaglutide is associated with significant improvement in kidney and survival outcomes in patients with type 2 diabetes and chronic kidney disease (CKD), including those with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or high total CVD risk, according to study results published in the Journal of the American College of Cardiology.

Researchers evaluated the effects of semaglutide on kidney outcomes and overall survival with data from the double-blind, randomized, placebo-controlled FLOW trial (Evaluate Renal Function with Semaglutide Once Weekly; ClinicalTrials.gov Identifier: NCT03819153).

Patients aged 18 years or older with CKD and type 2 diabetes were randomly assigned to 1.0-mg subcutaneous semaglutide once weekly or placebo. The prespecified analyses evaluated subgroups of patients classified by the absence or presence of baseline ASCVD. HF categories and high total CVD risk (defined as a 10-year PREVENT score of ≥20%) also were assessed.

The primary outcome was the composite of major adverse kidney events that included kidney failure (eGFR <15 mL/min/1.73 m², dialysis, transplantation), 50% or more estimated glomerular filtration rate (eGFR) decrease from baseline (≥28 days), and kidney or cardiovascular death.

Semaglutide is an important cardiovascular-kidney-metabolic therapeutic strategy because of the totality of kidney, cardiovascular, and survival benefits for people with type 2 diabetes and CKD.

The cohort included 3533 patients (mean age, 66.6 years; 30% women; mean eGFR, 47.0 mL/min/1.73 m²) who had a median follow-up of 3.4 years. Of these patients, 33.9% had ASCVD and 19.2% had HF at baseline. Among patients with baseline high-density lipoprotein cholesterol measures and without baseline HF or ASCVD, 66.5% had high total CVD risk.

Semaglutide decreased the relative risk for the primary outcome by 24% overall (hazard ratio [HR], 0.76; 95% CI, 0.66-0.88; P =.0003), compared with placebo. Compared with placebo, the benefits of semaglutide on the primary outcome were consistent in patients with ASCVD (HR, 0.80; 95% CI, 0.63-1.02) and without ASCVD (HR, 0.74; 95% CI, 0.62-0.89; P_interaction =.62), in patients with HF (HR, 0.67; 95% CI, 0.49-0.93) and without HF (HR, 0.79; 95% CI, 0.67-0.93; P_interaction =.40), and in patients with high total CVD risk (HR, 0.73; 95% CI, 0.58-0.91) and without high total CVD risk (HR, 0.73; 95% CI, 0.49-1.08; P_interaction =.99).

For all-cause mortality, the relative risk decreased by 20% overall (HR, 0.80; 95% CI, 0.67-0.95; P =.0104). The benefits for all-cause mortality with semaglutide were consistent in patients with ASCVD (HR, 0.82; 95% CI, 0.63-1.07) and without ASCVD (HR, 0.78; 95% CI, 0.62-0.99; P_interaction =.79), in patients with HF (HR, 0.75; 95% CI, 0.54-1.05) and without HF (HR, 0.81; 95% CI, 0.66-0.99; P_interaction =.74), and in patients with high total CVD risk (HR, 0.71; 95% CI, 0.52-0.95) and without high total CVD risk (HR, 0.82; 95% CI, 0.47-1.43; P_interaction =.63) at baseline.

The relative risk of all-cause mortality was consistent according to HF subtype and New York Heart Association functional class for semaglutide (P_interaction =.87) vs placebo (P_interaction =.90).

Among several study limitations, subgroup analyses were not powered for these evaluations, and the HF and high total CV risk subgroups were not prespecified, limiting them to hypothesis-generating observations. Additionally, wide confidence intervals in some subgroups reduced reliability, and the FLOW population was predominantly older, male, and White.

“Semaglutide is an important cardiovascular-kidney-metabolic therapeutic strategy because of the totality of kidney, cardiovascular, and survival benefits for people with type 2 diabetes and CKD,” the investigators wrote.

Disclosure: The FLOW trial was funded by Novo Nordisk A/S. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on The Cardiology Advisor