No evidence for increased overall cancer risk with SGLT2 inhibitors
medwireNews: Results of a systematic review and meta-analysis suggest that patients with type 2 diabetes who are treated with sodium–glucose cotransporter 2 (SGLT2) inhibitors do not have a higher overall cancer risk than patients not receiving these therapies.
The researchers, led by Jiali Han (Indiana University, Indianapolis, USA), analyzed data from 34,569 participants of 46 randomized controlled trials (RCTs) comparing one of three SGLT2 inhibitors – canagliflozin, dapagliflozin, or empagliflozin – with placebo or another glucose-lowering therapy.
Over a mean follow-up period of 61 weeks, 1.78% of 22,359 patients receiving SGLT2 inhibitors developed cancer, compared with 1.55% of 12,228 participants in the comparator groups, giving a nonsignificant odds ratio (OR) of 1.14.
However, in prespecified subgroup analyses, SGLT2 inhibitors were significantly associated with increased overall cancer risk among 24,832 participants with a body mass index (BMI) of 30 kg/m2 or higher, with rates of 2.20% versus 1.75% (OR=1.23), suggesting that “SGLT2 inhibitors in general might increase the risk of overall cancer in obese individuals,” report the researchers in Diabetologia.
And when Han and colleagues assessed the risk for specific cancer types, participants receiving SGLT2 inhibitors were significantly more likely to develop bladder cancer than those treated with a comparator agent (0.08 vs 0.01%; OR=3.87), with a particularly strong association seen among those who were treated with empagliflozin (0.09 vs 0%; OR=4.49).
On the other hand, patients treated with canagliflozin had a significantly lower risk for gastrointestinal cancer than those receiving a comparator treatment (0.06 vs 0.28%; OR=0.15).
“Canagliflozin is not only a potent SGLT2 inhibitor but also possesses potent SGLT1 inhibitory activity,” explain the researchers, noting that “SGLT1 is expressed mainly in the gastrointestinal tract […] while SGLT2 is highly selectively expressed in the kidneys and less so in the gastrointestinal tract.”
“Therefore, these findings suggest that canagliflozin may protect against gastrointestinal cancer by suppressing the expression of both SGLT1 and SGLT2 in the gastrointestinal tract,” they speculate.
Nevertheless, Han and colleagues concede that “given the relatively short-term design of the RCTs included in the analysis, the long-term effects of SGLT2 inhibitors on cancer remain uncertain.”
And they conclude: “Future long-term prospective studies and post-marketing surveillance studies are warranted.”
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