Related Experiment Video

Updated: Jun 22, 2025

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Published on: May 2, 2025

No Differences in Kidney Function Decline Between People With Type 2 Diabetes Starting a Sodium-Glucose Cotransporter

Sara Bodini¹, Silvia Pieralice¹, Luca D'Onofrio¹

¹Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Clinical Therapeutics

|July 4, 2024

Abstract

Purpose:

Diabetic nephropathy represents the leading cause of end-stage kidney disease in developed countries. Cardiovascular outcome trials have found that in participants who received a glucagon-like peptide-1 receptor agonist (GLP1RA) and a sodium-glucose cotransporter 2 inhibitor (SGLT2i), the risk of incidence and progression of diabetic nephropathy in type 2 diabetes mellitus was reduced. The aim of this study was to compare the decline in estimated glomerular filtration rate (eGFR) among people taking a GLP1RA with that among people taking an SGLT2i in a real-world setting.

Methods:

Data for 478 patients with type 2 diabetes mellitus who initiated therapy with a GLP1RA (n = 254) or an SGLT2i (n = 224) between January 1, 2018 and December 31, 2021 were extracted. The primary outcome was any reduction ≥30% in eGFR after the start of therapy. Weight loss and drug discontinuation were also assessed.

Findings:

Over a median follow-up of 24 months, an eGFR reduction ≥30% occurred in 34 of 254 patients (13.4%) starting a GLP1RA and in 26 of 223 patients (11.6%) starting an SGLT2i (hazard ratio = 0.89; 95% CI, 0.54-1.49; P = 0.67). Median eGFR change over the whole follow-up was similar between groups (SGLT2i: median, -2 mL/min/1.73 m²; 25th, 75th percentile, -13, 8 mL/min/1.73 m²; GLP1RA: median, 0 mL/min/1.73 m²; 25th, 75th percentile, -10, 7 mL/min/1.73 m²; P = 0.54). No worsening of kidney function was observed, even when considering the ratio eGFR mean. The value of eGFR at baseline indicated a statistically significant indirect correlation with the observed absolute value of eGFR change over the follow-up (ρ = -0.36; P < 0.001). The difference in eGFR changes over time observed by eGFR categories was statistically significant (P = 0.0001) in both treatment groups. No significant differences in weight loss and drug discontinuations were observed between groups.

Implications:

Although acting on different molecular mechanisms, both GLP1RA and SGLT2i might have similar effects on eGFR decline in diabetes, as suggested by the results of the present study conducted in a real-world setting. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc.

Insights

Glucagon-like peptide-1 receptor agonists (GLP1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) showed similar effects on slowing estimated glomerular filtration rate (eGFR) decline in type 2 diabetes patients. This real-world study suggests comparable kidney protection for both drug classes.

Area of Science:

Nephrology
Endocrinology
Pharmacology

Background:

Diabetic nephropathy is a leading cause of end-stage kidney disease.
Cardiovascular outcome trials indicate GLP1RA and SGLT2i reduce diabetic nephropathy risk in type 2 diabetes.
Real-world data on comparative eGFR decline is needed.

Purpose of the Study:

To compare the decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes treated with GLP1RA versus SGLT2i.
To assess the real-world effectiveness of these drug classes in preserving kidney function.

Main Methods:

Retrospective analysis of 478 patients with type 2 diabetes initiating GLP1RA (n=254) or SGLT2i (n=224) therapy.
Primary outcome: ≥30% reduction in eGFR from baseline.
Secondary outcomes: weight loss and drug discontinuation rates.

Main Results:

Over 24 months median follow-up, ≥30% eGFR reduction occurred in 13.4% of GLP1RA users and 11.6% of SGLT2i users (HR=0.89, P=0.67).
Median eGFR change was similar between groups (GLP1RA: 0 mL/min/1.73 m², SGLT2i: -2 mL/min/1.73 m²).
No significant differences in weight loss or drug discontinuation were observed.

Conclusions:

Both GLP1RA and SGLT2i demonstrated similar effects on eGFR decline in a real-world setting.
These findings suggest comparable renoprotective potential for both drug classes in type 2 diabetes.
Further research may elucidate the specific mechanisms underlying these similar outcomes.

Read full analysis

Keywords:

Chronic kidney disease Diabetes mellitus Diabetic nephropathy GLP1RA Glucagon-like peptide-1 receptor agonist Nephroprotective action SGLT2i Sodium-glucose cotransporter 2 inhibitor

More Related Videos

Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes

Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes

Published on: June 25, 2017

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion

Published on: May 10, 2018

Related Concept Videos

Glucagon-like Receptor Agonists

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...

Oral Hypoglycemic Agents: Glinides

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...

Oral Hypoglycemic Agents: Biguanides and Glitazones

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...

Diabetes Mellitus: Type 2 and Gestational

Diabetes Mellitus: Type 2 and Gestational

Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...

Insulin: Dosing Regimen and Adverse Effects

Insulin: Dosing Regimen and Adverse Effects

Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...

Articles linked to this work by shared authors, journal, and citation graph.

Glucagon-like peptide-1 receptor agonist treatment is associated with lower frequency of diabetic peripheral neuropathy and neuropathic pain in type 2 diabetes.

Pain·2026

Medico Legal aspects on Low-Grade Biofilm Infection to MDR Nosocomial Prosthetic Joint Infection.

La Clinica terapeutica·2026

Increasing incidence and clinical burden of paediatric type 1 diabetes in Italy: insights from a large administrative database.

Acta diabetologica·2026

Diffusion-weighted magnetic resonance imaging as a promising technique for detection and follow-up of liver metastases from neuroendocrine tumors: a retrospective and prospective study from the NETTARE task force.

Journal of endocrinological investigation·2026

Improved glycemic control with the MiniMed 780G system in latent autoimmune diabetes and type 1 diabetes: a real-world observational study.

Diabetes research and clinical practice·2026

Metabolomic profile differs between LADA and type 1 diabetes identifying tryptophan metabolism as a pathway involved in the heterogeneity of autoimmune diabetes.

Diabetologia·2026

See all related articles