Metabolic and renal effects of combined SGLT-2 inhibitors and GLP1-R agonists therapy in type 2 diabetes: a real-world analysis across DKD and non-DKD patients

L Mazzeo^#^{1

2}, S Wolde Sellasie^#^{2

3}, C Pecchioli², P Di Perna², S Zaccaria^{2

3}, P Sperti², I Nardone^{2

3}, L Giurato², D Della-Morte^{4

5

6}, M Caprio^{7

8}, A Bellia^{9

10}, L Uccioli²

Affiliations

¹ Department of Systems of Medicine, University of Tor Vergata, Viale Oxford 81, Rome, 00133, Italy.
² Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy.
³ PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy.
⁴ Division of Geriatrics, Department of Medical Sciences, University Hospital Fondazione Policlinico Tor Vergata, Viale Oxford 81, Rome, 00133, Italy.
⁵ Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, 00133, Italy.
⁶ Department of Neurology, Evelyn F. McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
⁷ Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, Rome, Italy.
⁸ Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Rome, 00166, Italy.
⁹ Department of Systems of Medicine, University of Tor Vergata, Viale Oxford 81, Rome, 00133, Italy. bellia@med.uniroma2.it.
¹⁰ Division of Endocrinology and Diabetology, Department of Medical Sciences, University Hospital Fondazione Policlinico Tor Vergata, Viale Oxford 81, Rome, 00133, Italy. bellia@med.uniroma2.it.

^# Contributed equally.

PMID: 41452441
DOI: 10.1007/s40618-025-02756-5

Metabolic and renal effects of combined SGLT-2 inhibitors and GLP1-R agonists therapy in type 2 diabetes: a real-world analysis across DKD and non-DKD patients

L Mazzeo et al. J Endocrinol Invest. 2025.

. 2025 Dec 26.

doi: 10.1007/s40618-025-02756-5. Online ahead of print.

Authors

Affiliations

¹ Department of Systems of Medicine, University of Tor Vergata, Viale Oxford 81, Rome, 00133, Italy.
² Division of Endocrinology and Diabetes, CTO Andrea Alesini Hospital, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy.
³ PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy.
⁴ Division of Geriatrics, Department of Medical Sciences, University Hospital Fondazione Policlinico Tor Vergata, Viale Oxford 81, Rome, 00133, Italy.
⁵ Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, 00133, Italy.
⁶ Department of Neurology, Evelyn F. McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
⁷ Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, Rome, Italy.
⁸ Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Rome, 00166, Italy.
⁹ Department of Systems of Medicine, University of Tor Vergata, Viale Oxford 81, Rome, 00133, Italy. bellia@med.uniroma2.it.
¹⁰ Division of Endocrinology and Diabetology, Department of Medical Sciences, University Hospital Fondazione Policlinico Tor Vergata, Viale Oxford 81, Rome, 00133, Italy. bellia@med.uniroma2.it.

^# Contributed equally.

PMID: 41452441
DOI: 10.1007/s40618-025-02756-5

Abstract

Purpose: This study aimed to evaluate the one-year metabolic and renal effects of combined therapy with SGLT-2 inhibitors and GLP-1 receptor (GLP-1R) agonists in patients with type 2 diabetes mellitus (T2DM), both with and without diabetic kidney disease (DKD). The primary objective was to assess changes in BMI, HbA1c, LDL-C, eGFR, and UACR in a real-world setting.

Methods: A retrospective analysis was conducted on 250 patients with type 2 diabetes mellitus (T2DM) treated with SGLT-2 inhibitors and GLP-1 receptor agonists at the Diabetology Service of CTO-Alesini Hospital, Rome, between 2022 and 2025. Metabolic and renal parameters were collected at baseline and after 12 months. Patients were stratified according to the presence of diabetic kidney disease (DKD). The primary outcomes included changes in BMI, HbA1c, LDL-C, eGFR, and UACR. Secondary analyses evaluated the impact of adding an SGLT-2 inhibitor to pre-existing GLP-1 receptor agonist therapy, or vice versa.

Results: After 12 months, we observed significant reductions in BMI (p = 0.03), HbA1c (p < 0.001), LDL-C (p < 0.01), and UACR (p < 0.001). In patients with DKD (46% of the cohort), UACR improved markedly (p < 0.001), while eGFR remained stable. Significant reductions in HbA1c (p < 0.001) and LDL-C (p < 0.01) were also observed. In non-DKD patients, HbA1c and LDL-C decreased after one year, with eGFR remaining within the normal range. Importantly, among DKD patients, the addition of an SGLT-2 inhibitor to GLP-1 receptor agonist therapy resulted in significant reductions in both HbA1c (p = 0.04) and UACR (p < 0.01), whereas the addition of a GLP-1 receptor agonist primarily reduced HbA1c (p < 0.01). In non-DKD patients, both treatment sequences improved HbA1c and LDL-C.

Conclusion: Dual therapy with SGLT-2 inhibitors and GLP-1 receptor agonists was associated with improvements in glycemic control, lipid profile, and albuminuria, particularly among patients with DKD. The sequence of drug addition appeared to influence outcomes, with the addition of SGLT-2 inhibitors providing superior renal benefits in DKD. These findings may provide support for early combined use of both agents in high-risk patients with T2DM.

Keywords: Diabetic kidney disease; GLP-1 receptor agonists; SGLT2 inhibitors; Type 2 diabetes mellitus.

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Conflict of interest statement

Declaration. Conflicts of interest: The authors declare no conflicts of interest. Informed consent: Informed consent was not required in accordance with the Italian regulation for non-interventional (observational) retrospective studies concerning human beings (AIFA Guidelines for Observational Studies, see www.AIFA.gov).

References

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1. Antonazzo IC et al (2024) Generalizability and treatment with sodium-glucose co-trasporter-2 inhibitors (SGLT2i) among patients with type 2 diabetes: an assessment using an Italian primary care database, Acta Diabetol, 62(3), pp. 343–351, Aug. https://doi.org/10.1007/s00592-024-02359-1
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Metabolic and renal effects of combined SGLT-2 inhibitors and GLP1-R agonists therapy in type 2 diabetes: a real-world analysis across DKD and non-DKD patients

Affiliations

Metabolic and renal effects of combined SGLT-2 inhibitors and GLP1-R agonists therapy in type 2 diabetes: a real-world analysis across DKD and non-DKD patients

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous