Limitations

Letters to the Editor Gliflozins for the Treatment of Congestive Heart Failure and Renal Failure in Type 2 Diabetes by Anna Katharina Seoudy, Prof. Dr. med. Dominik M. Schulte, Dr. med. Tim Hollstein, Dr. med. Ruwen Böhm, Prof. Dr. med. Dr. rer. nat. Ingolf Cascorbi, and Prof. Dr. med. Matthias Laudes in issue 8/2021

The authors describe a notable cardiovascular benefit of treatment with gliflozins (SGLT2 inhibitors) in patients with type 2 diabetes (1). The following limitations apply.

All included studies compared the SGLT2 inhibitor with placebo. A useful benefit assessment is only possible, however, by comparison with established therapies. Furthermore, a placebo comparison in patients with heart failure is ethically unsound, since SGLT2 inhibitors are strong diuretics and such patients naturally benefit from these drugs.

The design of all included SGLT2 inhibitor studies enables immediate peripheral unblinding—that is, knowledge of the actually assigned study medication in the center with the possibility of non-equivalent treatment and assessment of both study arms. This detail is important, because the endpoint “hospitalization or urgent outpatient treatment for heart failure” is subject to the subjective assessment of the investigator and may lead to different conclusions if the study medication is known. Anticipatory changes to the accompanying medication in this indication may or may not prevent hospital admission. There are credible reports that individual study centers manipulate their results (2). Furthermore we have known since the TOPCAT study (3) and its successor publication (4), that study results of individual countries can substantially affect the overall results of a study, and that traditional methods of data validation are not sufficient to recognize incorrect data and exclude these from the study.

The real value of the SGLT2 inhibitors will be known only after methodologically sound studies that compare these drugs with suitable medications. Data reliability will improve if clinical studies share the individual study centers, their inclusion numbers, and their results before and after the central validation process. In the digital age, such information in the appendix is no publishing challenge.

DOI: 10.3238/arztebl.m2021.0195

Dr. med. Philipp Conradi

Allgemenmedizin

Dresden

Conflict of interest statement

The author declares that no conflict of interest exists.

References

1. Seoudy AK, Schulte DM, Hollstein T, Böhm R, Cascorbi I, Laudes M: Gliflozins for the treatment of congestive heart failure and renal failure in type 2 diabetes. Dtsch Arztebl Int 2021; 118: 122–9

2. Ahr N, Hawranek C: Eine Überdosis Risiko. Die Zeit vom 13. 03. 2014.

3. Pitt B, Pfeffer M, Assmann S, et al.: Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014; 370: 1383–92

4. Pfeffer M, Claggett B, Asmann S, et al.: Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosteron antagonist (TOPCAT) Trial. Circulation 2015; 131: 34–42