Are black people well represented in SGLT-2i clinical trials?

Summary

The estimated global representation of Black participants in clinical trials is 5.4% The average Black participation in SGLT-2i clinical trials is 3.4%, lower than the global clinical trial average

Summary

  • The estimated global representation of Black participants in clinical trials is 5.4%
  • The average Black participation in SGLT-2i clinical trials is 3.4%, lower than the global clinical trial average
  • Given the increased incidence of T2D and related diseases in black people, hinting at a potential increased benefit, SGLT-2i trials with increased black participation are sorely needed to determine efficacy and safety and inspire confidence. 

“SGLT-2i trials with increased black participation are sorely needed to determine efficacy and safety”

The SGLT-2i class as diabetes medications

The sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are a relatively novel class of medications, with the first marketing authorisations granted in 2012 (1). The class are were initially indicated for the treatment of Type 2 Diabetes, and now more recently adding Type 1 diabetes to their repertoire. 

The class have demonstrated efficacy in reducing blood glucose concentrations and have additional effects of significantly reducing blood pressure and body weight (1–3). 

More recently, as a result of the SGLT-2i cardiovascular outcome trials (CVOTs) (4–6), and investigations into renal outcomes (7,8), the class is being embedded as one offering cardiovascular (CV) and renal protection to patients with Type 2 diabetes. Well established institutions such as the  American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) now advocate for SGLT-2i use in eligible patients with established atherosclerotic CV disease (ASCVD), heart failure or chronic kidney disease (CKD) (9).  

"Given the increased incidence of obesity, hypertension, CVD and CKD in black people, the SGLT-2i class seems an obvious choice in those with Type 2 diabetes who qualify. However, are the SGLT-2i clinical trial populations representative enough to provide confidence of efficacy?"

Given evidence of an increased incidence of diabetes(10), obesity, hypertension, CVD and CKD(11,12) in black and African American people; the SGLT-2i class seems an obvious choice in those with Type 2 diabetes who qualify. However, are the SGLT-2i clinical trial populations representative enough to provide confidence of safety and efficacy?

Do SGLT-2i trials adequately represent black people?

There has been a longstanding debate about whether race has an impact on drug metabolism, efficacy and safety(13–15); as the jury is still out, representation of Black people in clinical trials is important. This is especially true for the SGLT-2i class, where there is often a clinical need for the additional class benefits. 

An FDA report estimates the representation of Black or African American participants in clinical trials to be 14.5% in US trial sites and 5.4% globally(16).

FDA Global Participation in Clinical Trials Report 2017

Representation of Black or African American participants drops to 1.3% when excluding trial sites in the USA(16). 

When looking at the black participation rates in SGLT-2i clinical trials, the average is below the global average inclusion in clinical trials. 

Given the increased incidence of T2D and related diseases in black people, the potential for the SGLT-2i class to offer increased benefit, and the current low participation in clinical trials, SGLT-2i trials with increased black participation are sorely needed to determine efficacy and safety, and to inspire confidence.

References

  1. Forxiga 5 mg film-coated tablets – Summary of Product Characteristics (SmPC) – (eMC) [Internet]. [cited 2019 Jun 30]. Available from: https://www.medicines.org.uk/emc/product/2865/smpc
  2. Jardiance 10 mg film-coated tablets – Summary of Product Characteristics (SmPC) – (eMC) [Internet]. [cited 2019 Jun 30]. Available from: https://www.medicines.org.uk/emc/product/5441/smpc
  3. Invokana 100 mg and 300 mg film-coated tablets – Summary of Product Characteristics (SmPC) – (eMC) [Internet]. [cited 2019 Jun 30]. Available from: https://www.medicines.org.uk/emc/product/8855/smpc
  4. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019 Jan 24;380(4):347–57.
  5. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644–57.
  6. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117–28.
  7. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019 Jun 13;380(24):2295–306.
  8. Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):323–34.
  9. Davies MJ, D’Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec 1;41(12):2669 LP – 2701.
  10. Center for Health Statistics N. Table A-4. Selected diseases and conditions among adults aged 18 and over, by selected characteristics: United States, 2017. 2017.
  11. Cossrow N, Falkner B. Race/Ethnic Issues in Obesity and Obesity-Related Comorbidities. J Clin Endocrinol Metab. 2004 Jun 1;89(6):2590–4.
  12. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart Disease and Stroke Statistics—2015 Update. Circulation. 2015 Jan 27;131(4).
  13. Genes, drugs and race. Nat Genet. 2001;29(3):239–40.
  14. Hunt SY. Pharmacogenetics, Personalized Medicine, and Race. Nat Educ. 2008;1(1):212.
  15. Ramamoorthy A, Pacanowski M, Bull J, Zhang L. Racial/ethnic differences in drug disposition and response: Review of recently approved drugs. Clin Pharmacol Ther. 2015 Mar 1;97(3):263–73.
  16. FDA, CDER. GLOBAL PARTICIPATION IN CLINICAL TRIALS REPORT http://www.fda.gov Global Participation in Clinical Trials Report. 2017.

 

 

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