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A Review on the Relationship between SGLT2 Inhibitors and Cancer
Hao-Wen Lin1, Chin-Hsiao Tseng2
1Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan.
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.
Insights
Sodium glucose cotransporter type 2 (SGLT2) inhibitors may pose a cancer risk. Further research is needed to determine if observed breast and bladder cancer increases with SGLT2 inhibitors are a class effect or due to early diagnosis.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- Sodium glucose cotransporter type 2 (SGLT2) inhibitors are a novel class of antidiabetic agents.
- Concerns regarding potential increased risks of breast and bladder cancer have been raised for SGLT2 inhibitors.
- Preclinical studies of dapagliflozin showed an imbalance in female breast and male bladder cancers, hindering its FDA approval.
Purpose of the Study:
- To review existing literature on the cancer risk associated with SGLT2 inhibitors.
- To evaluate whether observed cancer imbalances are a class effect or specific to certain drugs.
- To determine the conclusive relationship between SGLT2 inhibition and cancer formation.
Main Methods:
- A literature search was conducted using PubMed for studies published before January 29, 2014.
- Reviewed preclinical and clinical data for SGLT2 inhibitors, specifically dapagliflozin and canagliflozin.
- Assessed cancer incidence data in relation to SGLT2 inhibitor use.
Main Results:
- Preclinical studies of dapagliflozin indicated potential, though not statistically significant, increases in female breast and male bladder cancers.
- New clinical data suggests that observed imbalances may be due to earlier cancer diagnosis rather than increased incidence.
- Canagliflozin showed no increased risk of overall bladder or breast cancer.
Conclusions:
- The observed cancer imbalance with dapagliflozin should not be extrapolated as a class effect for all SGLT2 inhibitors.
- The relationship between SGLT2 inhibition and cancer requires further investigation on a drug-by-drug basis.
- Larger, longer-term studies across diverse ethnicities are warranted to definitively establish the cancer risk of SGLT2 inhibitors.
