Cardio-renal benefits of newer glucose lowering agents may be less effective in Black people

Abstract

Recent advances in diabetes pharmacotherapy have provided clinicians with newer therapies to manage hyperglycaemia in patients with type 2 diabetes. Unlike previous agents, these new therapies such as sodium–glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) have been shown to provide cardio-renal benefits beyond their glucose lowering abilities. As well as their superior efficacy in lowering blood glucose levels in a glucose dependant manner (i.e., lower risks of hypoglycaemia), these agents have been shown to confer significant cardiovascular and renal benefits in addition to their weight loss effects. However, whether their efficacy was similar across different racial and ethnic groups remains unclear. To answer this question, researchers from Leicester have undertaken a systematic meta-analysis of 14 randomized placebo-controlled trials of SGLT2-Is and GLP1-RAs—seven trials for each drug—that had reported cardiovascular and renal outcomes by race or ethnicity.

Their study, published in the Journal of the Royal Society of Medicine (1) showed that for White and Asian populations, SGLT2-Is and GLP1-RAs had beneficial effects on blood pressure, weight control, and renal function, and significantly reduced the risk of major adverse cardiovascular events and kidney disease. Interestingly however, evidence of these beneficial effects in Black populations was not seen. Specifically, they reported no significant improvements for Black patients, with either drug, in the number of major adverse cardiovascular events, a composite CVD death/heart failure hospitalization measure, or the composite renal outcome (end-stage kidney disease, doubling of creatinine level, or death from renal causes), with the exception of a reduction in heart failure hospitalisations on SGLT2-Is. It is important to note however that the proportion of black patients is quite low (2.4% to 8.3%) compared with 66.6% to 93.2% for White populations, 1.2% to 21.6% for Asian populations, and 0.9% to 23.1% for ‘other’ populations. Thus, it seems that evidence from these landmark trials may be less generalizable to the black populations due to their under-representation in these trials. The latter is an important consideration because differences in the prevalence of type 2 diabetes (T2D), its risk factors, its microvascular and macrovascular complications, and associated mortality are well recognized between different ethnic groups. For example, Black people are more likely to develop T2D at a younger age, have higher risks of developing hypertension, more likely to have lower extremity amputations and to develop retinopathy and nephropathy. Whether observation from this study is mainly driven by low statistical power or due to genuine differences in genetic, pharmacokinetics, pharmacodynamics, and safety of SGLT2-Is and GLP1-Ras in this patient group is unknown. However it is important to note that Black populations are also well-known to have a higher prevalence of major cardiovascular risk factors such as hypertension, dyslipidaemia, smoking, physical inactivity, and additional co-morbidities, compared with White populations. Aggressive cardio-renal management of this patient group with lipid and blood pressure lowering agents, in addition to glucose and weight lowering strategies is therefore crucial. Further studies are therefore required to assess the efficacy of newer glucose lowering therapies among black population as well as to enhance representation of ethnic minorities group in these large landmark trials to ensure evidence can be generalized to all ethnic groups.