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In a recent meta-analysis of 12 observational studies of patients with T2DM treated with either SGLT2 inhibitors or GLP-1RAs, the GLP-1RA group exhibited a significantly lower relative risk of lower limb amputation vs the SGLT2 inhibitor cohort (3.54 vs 4.72 events per 1000 patient-years).37 Furthermore, in the CANVAS program involving 10,142 patients with T2DM at high cardiovascular risk, canagliflozin was found to be associated with a 1.97-fold increased risk of lower-limb amputations
Despite the Biden administration's 2024 proposal to reinterpret the statutory exclusion of weight-loss drugs, the Trump administration declined to finalize that change in April 2025
In the trial, participants with type 2 diabetes who took 15 mg of tirzepatide who had weight/obesity issues for less than 10 years lost 13% of their body weight compared to 16% of those with a disease duration of 10 to 20 years and 17% for more than 20 years
