Nat Med
January 2025
Aim: To evaluate the albuminuria-lowering effect of dapagliflozin, exenatide, and the combination of dapagliflozin and exenatide in patients with type 2 diabetes and microalbuminuria or macroalbuminuria.
Methods: Participants with type 2 diabetes, an estimated glomerular filtration rate (eGFR) of more than 30 ml/min/1.73m and an urinary albumin: creatinine ratio (UACR) of more than 3.
Chronic kidney disease (CKD) and heart failure affect many people worldwide. Despite the availability of pharmacological treatments, both diseases remain associated with considerable morbidity and mortality. After observations that sodium-glucose co-transporter 2 (SGLT2) inhibitors - originally developed as glucose-lowering agents - improved cardiovascular and renal outcomes in patients with type 2 diabetes, dedicated trials were initiated to evaluate the cardiovascular and kidney protective effects in patients with CKD or heart failure.
View Article and Find Full Text PDFDiabetes Obes Metab
August 2021
Aims: To evaluate the effects of separate and combined use of the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin and the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide on measures of kidney function.
Methods: In this prespecified secondary analysis of the DECREASE trial, we enrolled 66 obese patients with type 2 diabetes in a 16-week randomized double-blind placebo-controlled clinical trial to investigate the effects of dapagliflozin and exenatide twice daily, alone or in combination, versus placebo on 24-hour urinary albumin:creatinine ratio (UACR), creatinine and cystatin C-estimated glomerular filtration rate (GFR) and kidney injury molecule-1:creatinine ratio (KIM-1:Cr).
Results: At week 16, the mean UACR change from baseline was -39.
High protein intake may increase intraglomerular pressure through dilation of the afferent arteriole. Sodium-glucose cotransporter-2 (SGLT2) inhibitors may reduce intraglomerular pressure through activation of tubuloglomerular feedback. Given these opposing effects, we assessed whether the effect of dapagliflozin on glomerular filtration rate (GFR) and urinary albumin-to-creatinine ratio (UACR) was modified by estimated dietary protein intake using data from three separate randomized controlled trials (DELIGHT, IMPROVE and DIAMOND).
View Article and Find Full Text PDFThe effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on renal outcomes in patients with type 2 diabetes at high cardiovascular risk are modest or neutral. However, GLP-1RAs may confer clinical benefits in those at high risk of progressive renal function loss. We examined the effects of once-weekly exenatide (EQW) on estimated glomerular filtration rate (eGFR) slope and urinary albumin:creatinine ratio (UACR) as a function of baseline UACR in 3503 EXSCEL participants (23.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
September 2020
Sodium-glucose cotransporter 2 -inhibitors (SGLT2i) are oral glucose-lowering drugs that have also demonstrated cardioprotective and renoprotective effects. SGLT2i play an increasingly important role in the treatment of type 2 diabetes. Here we report a simple and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of three SGLT2i (canagliflozin, dapagliflozin and empagliflozin) in human plasma, serum and urine with a runtime of 1 min.
View Article and Find Full Text PDFDiabetes Obes Metab
September 2020
Aims: To examine the albuminuria-lowering effect of exenatide once weekly (EQW) compared with active glucose-lowering comparators in patients with type 2 diabetes and elevated urinary albumin-to-creatinine ratio (uACR).
Methods: Six randomized double-blind and open-label phase III studies were pooled in a post hoc, exploratory analysis to evaluate the efficacy and safety of EQW versus non-glucagon-like peptide-1 receptor agonist comparators in patients with type 2 diabetes and baseline uACR ≥30 mg/g. Treatment groups were EQW versus all comparators pooled.