Atherosclerosis Plus (Jun 2024)

Glucagon-like Peptide-1 analogues and delipidation of coronary atheroma in statin-treated type 2 diabetic patients with coronary artery disease: The prespecified sub-analysis of the OPTIMAL randomized clinical trial

  • Yu Kataoka,
  • Satoshi Kitahara,
  • Sayaka Funabashi,
  • Hisashi Makino,
  • Masaki Matsubara,
  • Miki Matsuo,
  • Yoko Omura-Ohata,
  • Ryo Koezuka,
  • Mayu Tochiya,
  • Tamiko Tamanaha,
  • Tsutomu Tomita,
  • Kyoko Honda-Kohmo,
  • Michio Noguchi,
  • Kota Murai,
  • Kenichiro Sawada,
  • Takamasa Iwai,
  • Hideo Matama,
  • Satoshi Honda,
  • Masashi Fujino,
  • Kazuhiro Nakao,
  • Shuichi Yoneda,
  • Kensuke Takagi,
  • Fumiyuki Otsuka,
  • Yasuhide Asaumi,
  • Kiminori Hosoda,
  • Stephen J. Nicholls,
  • Satoshi Yasuda,
  • Teruo Noguchi

Journal volume & issue
Vol. 56
pp. 1 – 6

Abstract

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Background and aims: Randomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet. Methods: The OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721). Of these, 78 patients with evaluable serial NIRS/IVUS images were analyzed to compare plaque measures between those treated with (n = 16) and without GLP-1RAs (n = 72). Results: All patients received a statin, and on-treatment LDL-C levels were similar between the groups (66.9 ± 11.6 vs. 68.1 ± 23.2 mg/dL, p = 0.84). Patients receiving GLP-1RAs demonstrated a greater reduction of HbA1c [-1.0 (-1.4 to −0.5) vs. −0.4 (-0.6 to −0.2)%, p = 0.02] and were less likely to demonstrate a glucose level >180 mg/dL [-7.5 (-14.9 to −0.1) vs. 1.1 (-2.0 - 4.2)%, p = 0.04], accompanied by a significant decrease in remnant cholesterol levels [-3.8 (-6.3 to −1.3) vs. −0.1 (-0.8 - 1.1)mg/dL, p = 0.008]. On NIRS/IVUS imaging analysis, the change in percent atheroma volume did not differ between the groups (−0.9 ± 0.25 vs. −0.2 ± 0.2%, p = 0.23). However, GLP-1RA treated patients demonstrated a greater frequency of maxLCBI4mm regression (85.6 ± 0.1 vs. 42.0 ± 0.6%, p = 0.01). Multivariate analysis demonstrated that the GLP-1RA use was independently associated with maxLCBI4mm regression (odds ratio = 4.41, 95%CI = 1.19–16.30, p = 0.02). Conclusions: In statin-treated patients with T2D and CAD, GLP-1RAs produced favourable changes in lipidic plaque materials, consistent with its stabilization.

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