Abstract
BACKGROUND: As indications for sodium-glucose co-transporter-2 inhibitors (SGLT2i) are expanding, a growing number of older adults have become candidates for treatment. We studied the safety profile of SGLT2i among older adults. METHODS: A retrospective, pharmacovigilance study of the FDA's global database of safety reports. To assess reporting of pre-specified adverse events following SGLT2i among adults (< 75 years) and older adults (≥ 75), we performed a disproportionality analysis using the sex-adjusted reporting odds ratio (adj.ROR). RESULTS: We identified safety reports of 129,795 patients who received non-insulin anti-diabetic drugs (NIAD), including 24,253 who were treated with SGLT2i (median age 60 [IQR: 51-68] years, 2,339 [9.6%] aged ≥ 75 years). Compared to other NIAD, SGLT2i were significantly associated with amputations (adj.ROR = 355.1 [95%CI: 258.8 - 487.3] vs adj.ROR = 250.2 [79.3 - 789.5]), Fournier gangrene (adj.ROR = 45.0 [34.5 - 58.8] vs adj.ROR = 88.0 [27.0 - 286.6]), diabetic ketoacidosis (adj.ROR = 32.3 [30.0 - 34.8] vs adj.ROR = 23.3 [19.2 - 28.3]), genitourinary infections (adj.ROR = 10.3 [9.4 - 11.2] vs adj.ROR = 8.6 [7.2 - 10.3]), nocturia (adj.ROR = 5.5 [3.7 - 8.2] vs adj.ROR = 6.7 [2.8 - 15.7]), dehydration (adj.ROR = 2.5 [2.3 - 2.8] vs adj.ROR = 2.6 [2.1 - 3.3]), and fractures (adj.ROR = 1.7 [1.4 - 2.1] vs adj.ROR = 1.5 [1.02 - 2.1]) in both adults and older adults, respectively. None of these safety signals was significantly greater in older adults (P(interaction) threshold of 0.05). Acute kidney injury was associated with SGLT2i in adults (adj.ROR = 1.97 [1.85 - 2.09]) but not in older adults (adj.ROR = 0.71 [0.59 - 0.84]). Falls, hypotension, and syncope were not associated with SGLT2i among either adults or older adults. CONCLUSION: In this global post-marketing study, none of the adverse events was reported more frequently among older adults. Our findings provide reassurance regarding SGLT2i treatment in older adults, although careful monitoring is warranted.