Too good to be true: Are GLP-1 receptor agonists the new metformin?

Abstract

Recently, a health-care database study showed that persons with type 2 diabetes taking GLP-1 receptor agonists (GLP-1 RA) had a significantly lower risk of 10 out of 13 obesity-related cancers than patients taking insulin (Wang L, et al. JAMA Netw Open. 2024 7: e2421305). For some cancers, hazard ratios <0.5 were reported. This is reminiscent of studies published >10 years ago showing that people with type 2 diabetes taking metformin had a lower risk of many types of cancer than those not taking metformin. In some studies, also risk reductions of >50 % were reported.

The strong effects observed in the metformin studies were explained by time-related biases, in particular, immortal time bias. In the current GLP-1 RA study, it was striking that the curves for the cumulative incidence of several cancers in GLP-1 RA and insulin users diverged immediately after therapy onset. This indicates that there is most likely a time-related bias: insulin is given at much later stages of type 2 diabetes than GLP-1 RA.

The current study suggests that one should be sceptical about database results when spectacular risk reductions are reported. Time-related bias should always be considered as an alternative explanation.