A Review on the Relationship between SGLT2 Inhibitors and Cancer

Abstract

Risk of increasing breast and bladder cancer remains a safety issue of SGLT2 (sodium glucose cotransporter type 2) inhibitors, a novel class of antidiabetic agent. We reviewed related papers published before January 29, 2014, through Pubmed search. Dapagliflozin and canagliflozin are the first two approved SGLT2 inhibitors for diabetes therapy. Although preclinical animal toxicology did not suggest a cancer risk of dapagliflozin and overall tumor did not increase, excess numbers of female breast cancer and male bladder cancer were noted in preclinical trials (without statistical significance). This concern of cancer risk hindered its approval by the US FDA in January, 2012. New clinical data suggested that the imbalance of bladder and breast cancer might be due to early diagnosis rather than a real increase of cancer incidence. No increased risk of overall bladder or breast cancer was noted for canagliflozin. Therefore, the imbalance observed with dapagliflozin treatment should not be considered as a class effect of SGLT2 inhibitors and the relationship with cancer for each specific SGLT2 inhibitor should be examined individually. Relationship between SGLT2 inhibition and cancer formation is still inconclusive and studies with larger sample size, longer exposure duration, and different ethnicities are warranted.

The Safety and Efficacy of SGTL2 Inhibitors in Diabetes Mellitus Management

“…As such women and men should be taught the benefits of good perineal hygiene and may even benefit from prophylactic therapy (7)(13). Importantly, while SGLT2i therapy predicates on diuresis to remove the additional glucose load the frequency of hypotensive episodes occur in only 1.2-1.3% of patients with no significant impact noted on the rate ofvenous thromboembolism events (10) Of some concern, observational studies have highlighted a trend to increased incidence of particularly bladder cancer in the long-term use of dapagliflozin (17). However this on further study has been found to not be significant as dapagliflozin has not been found to affect bladder cancer cell growth or survival.…”

“…However this on further study has been found to not be significant as dapagliflozin has not been found to affect bladder cancer cell growth or survival. Moreover, it has been found that SGLT1 is over expressed in many cancer types and its inhibition has been found to sensitize prostatic cancer cells to monoclonal and Tyrosine Kinase based therapy and in pancreatic adenocarcinoma significantly correlates with disease free survival (17).…”

Risk-Benefit Profile of Novel Anti-diabetic Drugs: Current Perspectives

“…As for pioglitazone, the potential cardiovascular benefit from the proactive study must be balanced against the documented increase of bladder cancer risk, a controversial and not fully understood adverse reaction also reported with gliflozins (especially dapagliflozin) [10]. Accordingly, the current European summary of product characteristics does not recommend the association of SGLT-2 inhibitors with pioglitazone as a precautionary measure [11].…”

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“…[1][2][3][4][5][6][7][8][10][11][12][13][14][15][16][17][18][19] Moreover, the long term consequences of persistent exposure of urinary tract including urinary bladder to hyperglycemic hypertonic urine are unknown although increased risk of bladder cancer has been reported. 19,20 I believe that constant presence of sugar, the most efficient fuel for cell growth may have promoted growth of bladder cancer in situ and rendered it to be manifested rather than initiating the onset.…”

“…[20][21][22][23][24][25][26][27][28] Severe hypercalcemia and hypernatremia may be attributed to dehydration and increase in uric acid excretion may be responsible for hypouricemia. Hypophosphatemia was secondary to phosohaturia and anion gap acidosis may be attributed to amino aciduria both being the characteristic manifestations of Fanconi Syndrome, a renal tubular defect which also caused proteinuria in this patient within a week of administration of Canagliflozin.…”