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Drugs to treat diabetes are well tolerated in teenagers

Study gives insight into long-term complications

Jo Carlowe

Thursday, 02 November 2017

Interventional drugs for teenage diabetics are well tolerated, a global study* reveals.

A research team, based across the UK, Canada and Australia, led the four-year AdDIT (Adolescent Type 1 Diabetes cardio-renal Intervention Trial) study, with the aim of understanding more about the development of long-term complications in young people with type 1 diabetes. Controlling levels of glucose can be particularly difficult to achieve during adolescence. Future heart and kidney problems can reduce life expectancy by 10-15 years.

To address this problem, AdDIT set out to study the risk of complications during puberty and find out if ACE inhibitors and statins, already used in adults, could reduce the risk of kidney, eye and cardiovascular disease in young people with type 1 diabetes.

The trial was designed to measure the levels of albumin in the urine. Teenagers with low levels of albumin in their urine were considered to be at low risk, and were followed for up to four years (known as the observational arm). Teenagers with high levels of albumin in their urine were invited to join the trial, where they received either a single drug or a combination of the two (known as the intervention arm).

The results, published today in the New England Journal of Medicine, suggest that neither ACE inhibitors nor statins significantly reduce the levels of albumin in the urine. This primary outcome provides important insight into type 1 diabetes in adolescents and potentially opens up other avenues of research to find ways to reduce the risk of complications in the future.

While the primary outcome of the trial was negative, the secondary outcomes suggest that the drugs may have important benefits. The team found that treatment with the ACE inhibitor resulted in a 43% reduction in the rates of progression to microalbuminuria. While this didn’t reach statistical significance, the team believe it may be of clinical relevance moving forward. Preventing even temporary cases of microalbuminuria is known to reduce the future risk of kidney and cardiovascular complications. Alongside this, unpublished data presented at the American Diabetes Association 77th Scientific Sessions in June suggests that treatment with the ACE inhibitor reduces the risk of microalbuminuria in the ‘high-risk’ intervention arm toward the risk of those in the ‘low-risk’ observational arm. High rates of abnormal lipid levels were also reduced with statin therapy, which could reduce long-term risk for cardiovascular complications. 

Future work is still needed to establish the full benefits of statins and ACE inhibitors in young people with type 1 diabetes, say the authors. The research team has suggested that the impact of ACE inhibitor or statin treatment may be felt later, as seen in other glucose-, lipid-, or blood pressure-lowering trials. They hope to follow participants for a further five to ten years, to determine the long-term effects of the treatments.

Professor David Dunger, lead researcher of the AdDIT trial in the UK, based at the University of Cambridge, said: “This has been an amazing international collaboration involving over 4,000 young people with type 1 diabetes and many collaborating physicians across three continents. Studies in adolescence are said to be challenging, but our young participants were fantastic, following a complex protocol and demonstrating that the interventional drugs were well tolerated for up to four years. The therapies reduced harmful lipid levels and the risk of progression to microalbuminuria, both thought to be predictors of future risk for renal, cardiovascular and retinal complications.”

“There is no reason to believe that these findings will not translate into long-term benefits, but follow-up of this unique cohort will be essential. The essential biological samples and data provided by the participants, overall totalling at more than 800 teenagers, will continue to inform our future understanding and our options for effective therapies for this vulnerable group of young people with type 1 diabetes.”

Dr Elizabeth Robertson, director of research at Diabetes UK, said: “We need to find ways to reduce the risk of complications for young people with type 1 diabetes. The AdDIT study has achieved excellent engagement amongst young people across three continents. While more work is needed to reach definitive answers, we’d like to take this moment to celebrate with everyone who has supported this research. Thank you for your dedication.”

The research, supported by JDRF, British Heart Foundation and Diabetes UK, involved 4,407 teenagers across three continents.

* Marcovecchio L, Chiesa ST, Bond S, et al. ACE inhibitors and statins in adolescents with type 1 diabetes. N Engl J Med 2017; 377:1733-1745 November 2, 2017. DOI: 10.1056/NEJMoa1703518

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