Liraglutide treatment reduced interleukin‐6 in adults with type 1 diabetes but did not improve established autonomic or polyneuropathy

• Published in: British journal of clinical pharmacology 2019-11, Vol.85 (11), p.2512-2523
• Main Authors: Brock, Christina, Hansen, Christian Stevns, Karmisholt, Jesper, Møller, Holger Jon, Juhl, Anne, Farmer, Adam Donald, Drewes, Asbjørn Mohr, Riahi, Sam, Lervang, Hans Henrik, Jakobsen, Poul Erik, Brock, Birgitte
• Format: Article
• Language: English
• Subjects: Adult; anti‐inflammation; Autonomic Nervous System - drug effects; Autonomic Nervous System - physiopathology; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - immunology; Diabetic Neuropathies - diagnosis; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - immunology; Diabetic Neuropathies - physiopathology; diabetic neuropathy; Double-Blind Method; Electric Stimulation; Electroencephalography; Evoked Potentials, Somatosensory - drug effects; Evoked Potentials, Somatosensory - physiology; Female; glucagon‐like peptide‐1 agonist; Humans; Incretins - administration & dosage; Interleukin-6 - blood; Interleukin-6 - immunology; interleukin‐6; liraglutide; Liraglutide - administration & dosage; Male; Median Nerve - drug effects; Median Nerve - physiopathology; Middle Aged; Original; Polyneuropathies - diagnosis; Polyneuropathies - drug therapy; Polyneuropathies - immunology; Polyneuropathies - physiopathology; Prospective Studies; Treatment Failure; Weight Loss - drug effects
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.14063

Aims Type 1 diabetes can be complicated with neuropathy that involves immune‐mediated and inflammatory pathways. Glucagon‐like peptide‐1 receptor agonists such as liraglutide, have shown anti‐inflammatory properties, and thus we hypothesized that long‐term treatment with liraglutide induced diminished inflammation and thus improved neuronal function. Methods The study was a randomized, double‐blinded, placebo‐controlled trial of adults with type 1 diabetes and confirmed symmetrical polyneuropathy. They were randomly assigned (1:1) to receive either liraglutide or placebo. Titration was 6 weeks to 1.2–1.8 mg/d, continuing for 26 weeks. The primary endpoint was change in latency of early brain evoked potentials. Secondary endpoints were changes in proinflammatory cytokines, cortical evoked potential, autonomic function and peripheral neurophysiological testing. Results Thirty‐nine patients completed the study, of whom 19 received liraglutide. In comparison to placebo, liraglutide reduced interleukin‐6 (−22.6%; 95% confidence interval [CI]: −38.1, −3.2; P = .025) with concomitant numerical reductions in other proinflammatory cytokines. However neuronal function was unaltered at the central, autonomic or peripheral level. Treatment was associated with −3.38 kg (95% CI: −5.29, −1.48; P