Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) have proven long-term nephroprotective effects in large prospective cardiovascular and renal outcome placebo-controlled trials, which follow a initial transient dip of estimated glomerular filtration rate. Nevertheless, case reports of acute kidney injury (AKI) associated with SGLT2i therapy were reported, leading the US Food and Drug Administration to publish a warning in 2016. Of note, the incidence of AKI events was not increased and often reduced in outcome trials that compared SGLT2i treatment with placebo. However, patients in real-life might be at higher risk because of a more frailty profile and a less strict supervision. In a meta-analysis of 9 cohorts from 8 observational studies worldwide, the relative risk of AKI was significantly reduced (HR 0.61, 95% CI 0.55–0.67, I² = 70%) in SGLT2i users (725 AKI events/68,802 patients) compared with non-users (treated with other glucose-lowering agents, including incretin-based compounds: 977 AKI events/67,458 patients). In conclusion, observational studies in real-world conditions confirm the results reported in placebo-controlled outcome trials and show a reduction in AKI episodes in patients with type 2 diabetes treated with SGLT2is compared with those treated with other glucose-lowering agents. Overall, the renal safety of SGLT2is should be acknowledged by physicians, even if dehydration should be avoided.