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. 2022 Aug 4;21:144. doi: 10.1186/s12933-022-01575-9

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — Diabetes CVOTs in the broader context of cardiology trials. PIONEER-6 was a small study (N = 3183) of short duration, designed to rule out excess risk of 3P-MACE, and not powered to demonstrate superiority. Certain diabetes CVOTs have shown cardiorenal protective effects that may arguably be comparable to outcomes with cardiorenal therapies [116], such as the relative risk reduction of CV events compared with statins [27, 30–32, 34, 143, 144] (A), or NNT to prevent CV events compared with statins, aspirin or antihypertensive therapy [27, 116, 145, 146] (B). For example, patients with diabetes and CVD in the LIPID trial had a 19% reduced risk of CHD death or nonfatal MI over 6 years with the statin pravastatin compared with placebo [143]; meta-analyses of secondary prevention in patients with diabetes in multiple statin trials have produced similar results [143, 144, 147]. 3P-MACE, 3-point major adverse CV event; CHD, coronary heart disease; CV, cardiovascular; CVOT, CV outcomes trial; GLD, glucose-lowering drug; GLP-1 RA, glucagon-like peptide-1 receptor agonist; MI, myocardial infarction; NNT, number needed to treat; NR, not reported; RCT, randomised control trial; SGLT2, sodium–glucose transporter 2. *Four RCTs (4S, CARE, Post-CABG and VA-HIT) for CHD death and nonfatal MI, and 3 RCTs (4S, CARE, Post-CABG) for CHD death. ^†Five RCTs (4S, CARE, LIPID, Post-CABG and VA-HIT). ^‡Includes 1 RCT that investigated a non-statin cholesterol-lowering drug. ^‖Three RCTs (4S, CARE, LIPID)