Repurposing sodium-glucose co-transporter 2 inhibitors (SGLT2i) for cancer treatment – A Review

Lau, Kristy T K; Ng, Lui; Wong, Jason; Loong, Herbert H.; Chan, Wendy; Lee, Chi H.; Wong, Carlos K. H.

doi:10.1007/s11154-021-09675-9

Cited by 27 publications

(23 citation statements)

References 52 publications

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“…In a previous RCT, SGLT2i was not associated with risk of all-cancer incidence 19 . However, a recent study indicated a benefit of SGLT2i in suppressing cell growth 20 . SGLT2i was also added to standard cancer therapies in human studies 21,22 , and currently, clinical trials investigating SGLT2i safety and efficacy in cancer treatment are underway 20 .…”

Section: Discussionmentioning

confidence: 99%

“…However, a recent study indicated a benefit of SGLT2i in suppressing cell growth 20 . SGLT2i was also added to standard cancer therapies in human studies 21,22 , and currently, clinical trials investigating SGLT2i safety and efficacy in cancer treatment are underway 20 . These informative studies suggest SGLT2i antitumor abilities should be thoroughly investigated in further comprehensive studies.…”

Section: Discussionmentioning

confidence: 99%

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Association of SGLT2 inhibitors with lower incidence of death in type 2 diabetes mellitus and causes of death analysis

Chung

Hsu

Chang

et al. 2022

Sci Rep

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Sodium-glucose cotransporter 2 inhibitor (SGLT2i) potentially decrease all-cause and cardiovascular death, however, associations with non-cardiovascular death remain unclear. Therefore, we investigated SGLT2i associations with death and the cause of death. We used the Taiwanese National Health Institutes Research database linked to the National Register of Deaths (NRD). Incident type 2 diabetes mellitus (T2DM) patients and propensity score matched T2DM SGLT2i and Dipeptidyl peptidase 4 inhibitor (DPP4i) users were investigated. The index year was the SGLT2i or DPP4i prescription date from May 2016. Patients were followed-up until death or December 2018. Deaths verified by the NRD and grouped accordingly. Multiple Cox proportional hazards models were used. In total, 261,211 patients were included in the population; 47% of the patients were female and the average age was 62 years. The overall incidence of all-cause death was 8.67/1000 patient-years for SGLT2i and 12.41 for DPP4i users during follow-up. After adjusting for potential risk factors in the propensity score matched population, SGLT2i users were associated with lower risks of all-cause death, cardiovascular death, cancer death, and non-cancer, non-vascular death compared with DPP4i-users. For specific death causes, significantly lower death risks from heart disease, cerebrovascular disease, and accidents were associated with SGLT2i-use. SGLT2i benefits for T2DM patients were not different across subgroups. Compared with DPP4i-use, SGLT2i-use for T2DM was associated with lower disease and death risk.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association of SGLT2 inhibitors with lower incidence of death in type 2 diabetes mellitus and causes of death analysis

Chung

Hsu

Chang

et al. 2022

Sci Rep

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“…In patients with co-existing T2D and CHB, it was recently shown that the use of SGLT2i was also associated with a reduced risk of incident hepatic events, defined as a composite of cirrhosis complications, HCC, and liver-related mortality 11 . Indeed, over the years, several preclinical studies had suggested anticarcinogenic effects of SGLT2i in some cancers such as HCC through changes in glucose metabolism, as well as modulation of molecular pathways that could limit tumor growth and induce cell death 12,13 . However, in another recent retrospective study comparing SGLT2i against dipeptidyl peptidase-4 inhibitors (DPP4i) among patients with T2D, in the subgroup of patients with co-existing CHB, the findings favored more toward DPP4i and the use of SGLT2i was associated with a higher risk of HCC 14 .…”

Section: Introductionmentioning

confidence: 99%

SGLT2i reduces risk of developing HCC in patients with co-existing type 2 diabetes and hepatitis B infection: A territory-wide cohort study in Hong Kong

et al. 2023

Self Cite

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Background and Aims: Type 2 diabetes (T2D) and chronic hepatitis B infection (CHB) are risk factors of HCC. Sodium glucose co-transporter 2 inhibitors (SGLT2i) inhibit HCC oncogenesis in preclinical studies. However, clinical studies are lacking. This study aimed to evaluate the impact of SGLT2i use on incident HCC using a territory-wide cohort of exclusively patients with co-existing T2D and CHB. Approach and Results: Patients with co-existing T2D and CHB between 2015 and 2020 were identified from the representative electronic database of the Hong Kong Hospital Authority. Patients with and without SGLT2i use were 1:1 matched by propensity score for their demographics, biochemistry results, liver-related characteristics, and background medications. Cox proportional hazards regression model was used to assess the association between SGLT2i use and incident HCC. A total of 2,000 patients with co-existing T2D and CHB (1,000 in each SGLT2i and non-SGLT2i group; 79.7% on anti-HBV therapy at baseline) were included after propensity-score matching. Over a follow-up of 3,704 person-years, the incidence rates of HCC were 1.39 and 2.52 cases per 100 person-year in SGLT2i and non-SGLT2i groups, respectively. SGLT2i use was associated with a significantly lower risk of incident HCC (HR 0.54, 95%CI: 0.33-0.88, p=0.013). The association remained similar regardless of sex, age, glycemic control, diabetes duration, presence of cirrhosis and hepatic steatosis, timing of anti-HBV therapy, and background antidiabetic agents including dipeptidyl peptidase-4 inhibitors, insulin, or glitazones (all p interaction>0.05). Conclusions: Among patients with co-existing T2D and CHB, SGLT2i use was associated with a lower risk of incident HCC.

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“…Dapagliflozin appeared to lower the incidence of respiratory system malignancies when compared to the control group, however, the difference was not statistically significant. By boosting the expression of SGLT2 in lung premalignancy and early stage lung adenocarcinoma [ 82 ], dapagliflozin may be able to inhibit glucose transport and hence reduce the rate at which cancer cells proliferate. Dapagliflozin may increase the overall risk of malignant tumors, with digestive tract malignancy being more probable.…”

Section: Sglt2 Inhibitors and Cancermentioning

confidence: 99%

Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control

Youssef

Yahya

Popoviciu

et al. 2023

IJMS

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The number of diabetic patients has risen dramatically in recent decades, owing mostly to the rising incidence of type 2 diabetes mellitus (T2DM). Several oral antidiabetic medications are used for the treatment of T2DM including, α-glucosidases inhibitors, biguanides, sulfonylureas, meglitinides, GLP-1 receptor agonists, PPAR-γ agonists, DDP4 inhibitors, and SGLT2 inhibitors. In this review we focus on the possible effects of SGLT2 inhibitors on different body systems. Beyond the diabetic state, SGLT2 inhibitors have revealed a demonstrable ability to ameliorate cardiac remodeling, enhance myocardial function, and lower heart failure mortality. Additionally, SGLT2 inhibitors can modify adipocytes and their production of cytokines, such as adipokines and adiponectin, which enhances insulin sensitivity and delays diabetes onset. On the other hand, SGLT2 inhibitors have been linked to decreased total hip bone mineral deposition and increased hip bone resorption in T2DM patients. More data are needed to evaluate the role of SGLT2 inhibitors on cancer. Finally, the effects of SGLT2 inhibitors on neuroprotection appear to be both direct and indirect, according to scientific investigations utilizing various experimental models. SGLT2 inhibitors improve vascular tone, elasticity, and contractility by reducing oxidative stress, inflammation, insulin signaling pathways, and endothelial cell proliferation. They also improve brain function, synaptic plasticity, acetylcholinesterase activity, and reduce amyloid plaque formation, as well as regulation of the mTOR pathway in the brain, which reduces brain damage and cognitive decline.

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Repurposing sodium-glucose co-transporter 2 inhibitors (SGLT2i) for cancer treatment – A Review

Cited by 27 publications

References 52 publications

Association of SGLT2 inhibitors with lower incidence of death in type 2 diabetes mellitus and causes of death analysis

Association of SGLT2 inhibitors with lower incidence of death in type 2 diabetes mellitus and causes of death analysis

SGLT2i reduces risk of developing HCC in patients with co-existing type 2 diabetes and hepatitis B infection: A territory-wide cohort study in Hong Kong

Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control

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