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Newer Diabetes Drugs May Have Less Benefit in Black People

Despite higher rates of cardiovascular disease (CVD) and diabetes among people of Black ethnic origin, they are less likely to reap the cardiorenal protective effects of newer diabetes drugs, according to an analysis from the Diabetes Research Centre at the University of Leicester.

Unlike older drugs such as metformin, whose microvascular and macrovascular benefits are exerted via glycaemic control, newer agents seem to offer glucose-independent cardio-renal protection. As well as superior efficacy in lowering blood glucose, with lower risks of hypoglycaemia, they have beneficial effects on blood pressure, weight control, and renal function, and significantly reduce the risk of adverse cardiovascular and renal outcomes.

However, the researchers said, it was not known whether the efficacy of these agents — particularly sodium–glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) — was similar across different racial and ethnic groups. So they conducted a systematic meta-analysis of 14 randomised 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.

"No Evidence of Beneficial Effects in Black Populations"

Their findings, published in the Journal of the Royal Society of Medicine, 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. However, there was "no evidence of these beneficial effects in Black populations".

Specifically, there were no significant improvements for Black patients, for 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.

The proportion of different ethnicities in the trials was highly variable, ranging from 66.6% to 93.2% for White populations, 1.2% to 21.6% for Asian populations, 2.4% to 8.3% for Black populations, and 0.9% to 23.1% for 'other' populations. However these "pivotal" trials on cardiovascular outcomes, which were the basis for the approval of these newer drugs, did not specifically take racial/ethnic variations into consideration.

Black People More Likely to Sustain Diabetic Complications

The team explained that there were known racial/ethnic differences in the prevalence of type 2 diabetes (T2D), its risk factors, its microvascular and macrovascular complications, and associated mortality. In the UK, prevalence is higher among Black and minority ethnic groups than in the White population, and Black people are more likely to develop T2D at a younger age and a lower adiposity burden. They are also more likely to have lower extremity amputations and to develop retinopathy and nephropathy.

Many factors could have contributed to the lack of evidence of beneficial effects of SGLT2-Is and GLP1-RAs in Black and other non-White populations, the researchers said. Low statistical power due to small sample sizes of these populations may be partly responsible. "It is quite clear from the current data that some racial/ethnic groups such as Black populations were underrepresented in all the included trials," pointed out lead researcher Samuel Seidu, professor in primary care diabetes and cardio-metabolic medicine at the University of Leicester.

However, the researchers said, "the consistent nature of the significant lack of beneficial effects across the majority of outcomes for Black populations" meant that other factors might also be at play. There may also be racial/ethnic variations in the pharmacokinetics, pharmacodynamics, and safety of SGLT2-Is and GLP1-Ras, as there are with various antihypertensive medications, for example – and this needed further investigation.

Black populations are also well-known to have a higher prevalence of major cardiovascular risk factors including hypertension, dyslipidaemia, smoking, physical inactivity, and additional co-morbidities, compared with White populations. They may therefore already have a higher baseline risk for developing adverse cardiovascular and renal events, and most of these factors require lifestyle modifications and cannot be controlled by the trial drugs.

Lack of Benefits Among Black Populations "Concerning"

"Given the well-documented evidence that Black and other ethnic minority populations are more likely to develop T2D and at a younger age, the consistent lack of benefits we observed among Black populations is concerning," said Prof Seidu."Minimising racial and ethnic variations in the cardiovascular and renal complications of type 2 diabetes requires targeted improved access to care and treatment for those most at risk."

"Whether the differences are due to issues with under-representation of Black populations and low statistical power, or to racial/ethnic variations in the way the body and these drugs interact with each other needs further investigation," he said. However, he stressed that it was important that prescribers did not deny these newer drugs to Black populations on the back of this research.

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