Cancerpatients have high incidence of comorbid diabetes mellitus (DM). Once twoillnesses coexist; the situation would become very complicated, and the mortalityrate would rise in a relatively geometrically progressive manner. Given the recent clinical trials andadjustments in heart failure guidelines, favoring a more prominent role of sodium-glucosecotransporter-2 inhibitor (SGLT2I), studies into the efficacy and safety of SGLT2I indifferent populations are of great interest. Indeed, SGLT2I has gained disseminated role in recentadvancement in pharmacologic intervention for medical care beyond initial role asanti-diabetic agent. The motivationfor conducting this study is currently well-described since a more focusedrationale that describes the existing literature in this area and the knowledgegap should this study attempts to address. Hence, the present work reports onestimates of the effect of SGLT2I on all cause death in Taiwanese individualswith DM plus cancer versus matched controls without SGLT2I in a retrospectivecohort study, which wouldpotentially have relevant clinical consequences and might be a relevant addition to the literatureand certainlynoteworthy.

Using Taiwan’s National Health Insurance ResearchDatabase to analyze the prognosis of cancer patients with coexisting DM,comparing those receiving SGLT2I with those who do not. After index-yearand matching (age, sex, some comorbidities and medications), the authors obtaintwo groups of 20,339 patients. 

  The cancer patients withDM for SGLT2I users were at a lower incidences of all-causedeath than the non- SGLT2I cohort (5.05vs. 8.39 per 100 person-years), corresponding to adjusted HR values of 0.64 (95% CI= 0.60-0.68).   We compared the risks of all-causedeath between the SGLT2I users and non- SGLT2I users in termsof several variables including sex, age, and the presence or absence ofcomorbidities and medications. In all stratifications, the risks of all-causedeath in the SGLT2I users werelower than those in the non- SGLT2I users, except for patients without metformin and with GLP-1-RA.   Table 3 showed the incidence andrisk of all-cause death after stratified with different cancer. Compared to non- SGLT2I cohort, SGLT2I user in tongue cancer, month cancer, colon cancer,liver cancer, lung cancer, bladder cancer, prostate cancer, uteri cancer,breast cancer, and others showed lower risk of all-causedeath in SGLT2I cohort.  

The majorfinding is that after performing Kaplan Meier analysis, SGLT2I users had a lower risk of all cause death,especially for those younger age. Interesting, uteri cancers tend to have ahigher protective risk reduction for death. Strengths of this study include theexamination of a clinically important outcome and a large sample size thatallows for the estimation of precise treatment effects. The concept is originaland important to the literature. Given thelargely number of patients in each group (20,339), the study is powered,especially considering the limited differences in baseline characteristicsbetween 2 groups. The currentstudies investigate the benefit of SGLT2I use in patients with DM with cancer for outcomes of mortality. Interesting,the protective effect is more obvious for those younger patients; furtherindicating that the beneficial effect is possibly comorbidity-independent Moreover,the beneficial survival effect of SGLT2I is across all patients using anti-diabetic agentsother than SGLT2I; further implying that such beneficial effect of SGLT2I can also be used forbailed-out purpose. The observation of more risk reduction in mortality amonguteri cancers is difficult to illustrate; either small case numbers in thisgroup contributing to statistical phenomenon or truly reflecting a novel findingdeserve further exploration. There isinformation on biological mechanisms and pharmacological treatments of SGLT2I and mortality among this specific patients. Role of atherosclerosis, inflammation, thrombosis, and associatedmorbidity and mortality has been well established among cancer patients. Indeed, several molecular signaling pathway of SGLT2I has been explored, such asanti-atherosclerosis, anti-inflammation, anti-oxidative effects. Thecurrent section does contain meaningful information about how the researchquestion was generated and possibly it is supported by the plausible biologicevidence. Nonetheless, the hypothesized statements should still be widelyexplored and investigated by future studies.