Bochum, 21. Juni 2016:
“Clinicians Should Think Twice Before Prescribing DPP-4 Inhibitors for Diabetes” titelt Joshua J Fenton (1), Herausgeber der Zeitschrift Evidence-Based Medicine (2). Er stellt eingangs fest, dass Sitagliptin in der TECOS-Studie, publiziert im New England Journal of Medicine (3), in kardiovaskulärer (CV) Hinsicht bei den CV Hochrisiko-Typ-2-Diabetespatienten gegenüber Plazebo weder inferiority noch superiority gezeigt hätte. Der weitere Text ist so formuliert, dass er auszugsweise im Original wiedergegeben werden soll:
….I wondered why a trial demonstrating the non-inferiority of sitagliptin to placebo merited appearance in the world’s highest impact general medical journal…… The TECOS investigators…. recruited about twice as many patients than was necessary to provide 90% power for the non-inferiority analysis of safety. Indeed, by recruiting over 14 000 patients, the trial was adequately powered for both non-inferiority and superiority analyses, which ultimately showed no significant difference in the primary composite cardiovascular outcome in the sitagliptin versus placebo groups. The HR in the per-protocol, safety analysis was 0.98 (95% CI 0.88 to 1.09, p<0.001 for non-inferiority), while the HR in the intention-to-treat, superiority analysis was 0.98 (95% CI 0.89 to 1.11, p=0.65). Thus, the very low p value for the non-inferiority analysis implies that the likelihood is very small that sitagliptin increases the risk of the composite cardiovascular outcome by the prespecified non-inferiority margin of 30% or greater……For Merck, which manufactures sitagliptin and funded the study, this is very good news.
…..As these results demonstrate, sitagliptin does not reduce cardiovascular risk in high-risk patients, as patients and clinicians should want, despite its demonstrated ability to lower blood glucose levels. Indeed, the study data remain consistent with a 9% increase in the composite cardiovascular outcome (95% CI 0.88 to 1.09), and a 20% increase in the secondary outcome of congestive heart failure (intention-to-treat HR 1.00, 95% CI 0.82 to 1.20, p=0.98). The latter finding is of particular concern, because a recent meta analysis (4) of five trials (including TECOS) found a summary OR of heart failure admission with DPP-4 treatment of 1.13 (95% CI 1.00 to 1.26). Thus, despite TECOS, data from clinical trials remaining consistent with an increased risk of heart failure admission with DPP-4 use, so clinicians (and regulators) should not be blindly reassured by the TECOS findings. …
…Clinicians should remain wary that DPP-4 inhibitors may increase patients‘ cardiovascular risk, particularly for congestive heart failure, and that these risks could be comparable with any potential long-term benefits of glucose reduction that DPP-4 inhibitors may help to achieve.
Soweit die kritische Stimme von Joshua J Fenton.
(2) Joshua J. Fenton: Clinicians Should Think Twice Before Prescribing DPP-4 Inhibitors for Diabetes.
Evidence Based Medicine 2016;21(3):81-82.
(3) Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 Diabetes.
N Engl J Med 2015;373:232–42.
(4) Li L, Li S, Deng K, et al. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies.
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