Diabetology & metabolic syndromeJul 31, 2026

Possible benefits of GLP-1 receptor activators and SGLT2 blockers for nerve damage in diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 3, 2026

Abstract

Diabetic neuropathy is linked to considerable patient burden and mortality.

Cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shifted focus towards cardiovascular and renal health.
Preclinical studies suggest potential roles for GLP-1RAs and SGLT2i in treating diabetic neuropathy and neuropathic pain.
Current evidence from small phase II randomized controlled trials does not clearly demonstrate favorable effects of GLP-1RAs and SGLT2i on neuropathic outcomes.
Real-world responses to GLP-1RA and SGLT2i treatments appear heterogeneous, with notable rates of non-responders and treatment discontinuation.
Several risks associated with GLP-1RAs and SGLT2i treatment in real-world settings require increased awareness among healthcare providers and patients.

Simplified

The management of type 2 diabetes (T2D) has recently witnessed a paradigm shift extending beyond blood glucose regulation towards cardiovascular and renal health targeted by cardiovascular outcome trials (CVOTs) of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Preclinical studies suggest a potential role for GLP-1RAs and SGLT2i in the treatment of diabetic neuropathy and neuropathic pain. However, to date largely only small-size phase II shorter-term randomized controlled trials (RCTs) of heterogeneous designs and quality have been performed, without clear evidence of favorable effect of both GLP-1RAs and SGLT2i on clinical and neurophysiological neuropathic outcomes. Moreover, responses to GLP1-RA and SGLT2i treatments in real‑world clinical practice appear heterogeneous, with relatively high rates of non-responders and discontinuation. Several possible risks associated with GLP-1RAs and SGLT2i treatment in real-world practice have been identified requiring increased attention by physicians, their professional societies, and patients alike. Unfortunately, the opportunity has been missed to use simple tools for the detection and monitoring of diabetic sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in the multiple published large-scale pivotal CVOTs. Diabetic neuropathy is linked to considerable patient burden and mortality, and there remains an unmet need for the disease modifying effects of novel pharmacotherapies derived from the pathogenetic concepts of diabetic neuropathy. In the future, when designing and conducting RCTs more emphasis should be placed on considering neuropathy as a serious and potentially life-threatening complication.

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Competing interests

Declarations. Ethics: Not applicable. Clinical trial number: Not applicable. Human Ethics and Consent to Participate declarations: Not applicable. Consent for publication: All authors have read and approved the final manuscript. Competing interests: DZ: Consultant: AstraZeneca, Bayer, Clexio, Grünenthal, GSK, Novaremed, Nevro, Novo Nordisk, Procter & Gamble, Syqe, TrigoCare, Viatris, Wörwag; Speaker: AstraZeneca, Daiichi Sankyo, Eva, Grünenthal, Nevro, Sanofi, Viatris, Wörwag; Research support: Wörwag. AS: Consultant: Astra Zeneca, Ascensia, Berlin Chemie, Boehringer Ingelheim, Glaxo Smith Kline, Grünenthal, Hoffmann-La Roche, Lilly, Novartis, Novo Nordisk, Sanofi, Wörwag Pharma. VS: Consultant: Angelini, AWP srl, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novo Nordisk, Servier, Schwarz Pharma, Theras Lifetech, TrigoCare and Wörwag Pharma. Speaker: Boehringer Ingelheim, Eli Lilly, Impeto Medical, Laborest, Nevro Medical, Pfizer, Sanofi, Theras Lifetech, Viatris, and Wörwag Pharma. Research funding from Biocure and Boehringer Ingelheim. ST: honoraria for educational meetings from Viatris, Worwag Pharma, Novo Nordisk, Merk, AstraZeneca, Nevro, P&G Health, Viatris, Medtronic and Grunenthal; consulting fees from Worwag Pharma, Grunenthal, Merz, unrestricted research grants from Viatris, Procter and Gamble and Withings. CB: honoraria for lectures, advisory board participation, and other support from Novo Nordisk, Boehringer Ingelheim, Astra Zeneca, Eli Lilly, Novartis, Amgen, Servier, Viatris, Zentiva, Wörwag.

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Possible benefits of GLP-1 receptor activators and SGLT2 blockers for nerve damage in diabetes

Abstract

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