Albuminuria-lowering effect of adding semaglutide on top of empagliflozin in individuals with type 2 diabetes: A randomized and placebo-controlled study.

Abstract

AIM:

To investigate whether combined treatment with empagliflozin (a sodium-glucose cotransporter-2 inhibitor) and semaglutide (a glucagon-like peptide-1 receptor agonist) can reduce urinary albumin-creatinine ratio (UACR) compared to treatment with empagliflozin alone in individuals with type 2 diabetes (T2D) and albuminuria.

METHODS:

We conducted a randomized, placebo-controlled, double-blind, parallel study including 60 individuals with T2D and albuminuria. All participants initiated open-label empagliflozin 25 mg once daily, on top of renin-angiotensin system inhibition, in a run-in period of 26 weeks. Subsequently, participants were randomized to semaglutide or placebo 1 mg once weekly for 26 weeks. The primary endpoint was change in UACR. Secondary endpoints were change in: (i) measured glomerular filtration rate (GFR); (ii) 24-hour systolic blood pressure; (iii) glycated haemoglobin (HbA1c) level; (iv) body weight; and (v) plasma renin and aldosterone levels.

RESULTS:

Addition of semaglutide to empagliflozin provided no additional change in UACR from randomization to end-of-treatment. The mean (95% confidence interval) difference in UACR was -22 (-44; 10)% (P = 0.15) between treatment groups. Neither GFR, 24-hour blood pressure, body weight, nor plasma renin activity was changed with semaglutide. HbA1c (-8 [-13; -3] mmol/mol; P = 0.003) and plasma aldosterone (-30 [-50; -3] pmol/L; P = 0.035) were reduced with semaglutide compared to placebo.

CONCLUSIONS:

Semaglutide added to empagliflozin did not change UACR, measured GFR, 24-hour systolic blood pressure, body weight or plasma renin levels in individuals with T2D and albuminuria. Semaglutide improved glycaemic control and plasma aldosterone levels compared to placebo.

• Authors: Suvanjaa Sivalingam, Victor Soendergaard Wasehuus, Viktor Rotbain Curovic, Martin Baek Blond, Tine W Hansen, Frederik Persson, Peter Rossing
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 26 Issue 1 Pg. 54-64 (Jan 2024) ISSN: 1463-1326 [Electronic] England
• PMID: 37722966 (Publication Type: Randomized Controlled Trial, Journal Article)
• Copyright: © 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Chemical References

• semaglutide
• empagliflozin
• Sodium-Glucose Transporter 2 Inhibitors
• Glycated Hemoglobin
• Renin
• Aldosterone
• Glucagon-Like Peptides
• Hypoglycemic Agents

Topics

• Humans
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Sodium-Glucose Transporter 2 Inhibitors (therapeutic use)
• Glycated Hemoglobin
• Albuminuria (etiology, complications)
• Renin (therapeutic use)
• Aldosterone (therapeutic use)
• Treatment Outcome
• Glucagon-Like Peptides (therapeutic use)
• Body Weight
• Double-Blind Method
• Hypoglycemic Agents (therapeutic use)