Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map

SPS commentary:

According to a commentary, metformin and sulfonylureas remain the most commonly prescribed non-insulin antidiabetes drugs worldwide, and this current study confirms that their effects on CV outcomes are largely neutral, with weak evidence of CV benefit with metformin (vs placebo) and possible CV harm with certain sulfonylureas. It suggest that it could be argued that drugs shown in RCTs to reduce CV outcomes and protect the kidneys should be the preferred first-line and second-line treatments at least in patients with established CVD, but it stresses that this argument has to be balanced against the low costs of older drugs, the fact that they have been in use for several years, and their familiarity compared with newer drugs. It states that perhaps the time has not yet come to lose metformin as the preferred first-line agent, considering its overall efficacy and CVD safety, weight neutrality, low risk of hypoglycaemia, and cost, although the continued use of sulfonylureas as a second-line treatment is clearly questionable, especially in people with established CVD It adds that the decision to use a particular drug or drug class must be tailored to the patient and should take into account the whole package of efficacy, not only the glucose-lowering effects but also the risks of hypoglycaemia, weight gain, tolerability, potential CVD and renal benefits, and cost-effectiveness. It concludes that the argument favouring the use of SGLT2 inhibitors and GLP-1 receptor agonists earlier in the disease pathway, specifically in individuals at high CV risk, is increasingly persuasive, but this approach will require re-evaluation of the extent to which older, traditional drugs are used in the management and treatment of diabetes. It notes that a more contentious issue is whether these arguments will also apply to low-risk individuals and whether differences within drug classes are relevant to clinical practice.