Colchicine and diabetes in patients with chronic coronary artery disease: insights from the LoDoCo2 randomized controlled trial.

Introduction: Despite optimal treatment, patients with chronic coronary artery disease (CAD) and diabetes mellitus (DM) are at high risk of cardiovascular events, emphasizing the need for new treatment options. The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduces cardiovascular risk in patients with chronic CAD. This analysis determines the efficacy of colchicine in patients with chronic CAD and DM as well as the effect of colchicine on the development of new-onset type 2 diabetes mellitus (T2DM).
Methods: The LoDoCo2 trial randomized 5,522 patients to placebo or colchicine 0.5 mg once daily, with a median follow-up of 28.6 months. The primary composite endpoint was cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven revascularization. The effect of its treatment in patients with and without DM was evaluated by including an interaction term in the model.
Results: A total of 1,007 participants (18.2%) had T2DM at baseline. The adjusted hazard ratio (HR) [(95% confidence interval (CI)] for the primary endpoint in the T2DM group was 1.52 (1.15-2.01, p  < 0.01) compared with the group without T2DM. The HR for the treatment effect on the primary endpoint was 0.87 (0.61-1.25) in participants with T2DM and 0.64 (0.51-0.80) in participants without diabetes ( p _interaction = 0.14). The incidence of new-onset T2DM was 1.5% (34 out of 2,270) in the colchicine group and 2.2% (49 out of 2,245) in the placebo group ( p  = 0.10).
Discussion: In conclusion, based on the current evidence, the beneficial effects of colchicine on cardiovascular endpoints are consistent regardless of DM status. The potential benefits of colchicine in preventing new-onset DM need further investigation. These findings are only hypothesis-generating and require larger prospective trials to confirm the results.
Competing Interests: AM reports membership of advisory boards of and/or consultancy for AstraZeneca, Bayer, Boehringer Ingelheim, and Novartis. AM will not accept personal fees; these fees will be donated to research. JE reports consulting/honoraria support from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, Janssen, Sanofi-Aventis, and Servier, and grants and/or in-kind support from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Janssen, and Sanofi-Aventis. PT reports grants, travel support, and honoraria from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer. CT reports membership of advisory boards and/or consultancy for AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. WB reports membership of advisory boards and/or honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Novo Nordisk, and Sanofi-Aventis. JC reports membership in advisory boards with Amgen and AstraZeneca. Author JT was employed by Cardialysis BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(© 2023 Mohammadnia, Los, Opstal, Fiolet, Eikelboom, Mosterd, Nidorf, Budgeon, Tijssen, Thompson, Tack, Simsek, Bax, Cornel and El Messaoudi.)