Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs. The
use of this class of drugs is on the rise. In addition to its benefits in treatment of type 2 diabetes, patients
treated with SGLT-2 inhibitors are also observed to have fewer adverse cardiovascular and renal outcomes.
Further, recently, laboratory studies indicate that SGLT2 inhibitors might also have cancer treatment benefits.
However, population level epidemiological studies to investigate the role of SGLT-2 inhibitors on cancer
prognosis have not been undertaken.
Given that lung cancer is the leading cause of cancer death in both men and women in the US and
SGLT2 inhibitors have been recently recognized as potent antioxidant agents, the objective of this study is to
test the new hypothesis that SGLT2 inhibitors may be associated with favorable outcomes for patients with
non-small cell lung cancer (NSCLC, the most common subtype of lung cancer). We propose to use the US
Surveillance Epidemiology and End Results (SEER) database linked with Medicare claims data, a unique
population-based source of information, to achieve our objective. We will focus on canagliflozin, the most
widely prescribed SGLT2 inhibitor, covered by most Medicare and insurance plans, to assess the influence of
canagliflozin on the prognosis of diabetes patients with NSCLC using an innovative instrumental variable
analysis approach. We will first examine whether canagliflozin is associated with better NSCLC prognosis
(including total mortality and lung-cancer specific mortality) relative to other types of diabetes pharmacologic
treatments (Specific aim 1). Further, we will assess whether canagliflozin in combination with metformin (an
oral drug widely used as a first-line therapy for type 2 diabetes) is related to better NSCLC prognosis as
compared to either drug alone (Specific aim 2). We expect that if the analysis reveals an improved prognosis in
patients with NSCLC treated with canagliflozin, this will inform the design of future clinical trials with the
potential to yield a paradigm shift in the management of patients with lung cancer. The analyses and methods
used for this study can be expanded in the future to a more comprehensive examination of other types of
cancer in relation to canagliflozin and other SGLT2 Inhibitors.
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