OBJECTIVE Both sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) demonstrated cardiovascular benefits in randomized controlled trials of patients with type 2 diabetes (T2D) generally <65 years old and mostly with cardiovascular disease. We aimed to evaluate the comparative effectiveness and safety of SGLT2i and GLP-1RA among real-world older adults. RESEARCH DESIGN AND METHODS Using Medicare data (April 2013–December 2016), we identified 90,094 propensity score–matched (1:1) T2D patients ≥66 years old initiating SGLT2i or GLP-1RA. Primary outcomes were major adverse cardiovascular events (MACE) (i.e., myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure (HHF). Other outcomes included diabetic ketoacidosis (DKA), genital infections, fractures, lower-limb amputations (LLA), acute kidney injury (AKI), severe urinary tract infections, and overall mortality. We estimated hazard ratios (HRs) and rate differences (RDs) per 1,000 person-years, controlling for 140 baseline covariates. RESULTS Compared with GLP-1RA, SGLT2i initiators had similar MACE risk (HR 0.98 [95% CI 0.87, 1.10]; RD −0.38 [95% CI −2.48, 1.72]) and reduced HHF risk (HR 0.68 [95% CI 0.57, 0.80]; RD −3.23 [95% CI −4.68, −1.77]), over a median follow-up of ∼6 months. They also had 0.7 more DKA events (RD 0.72 [95% CI 0.02, 1.41]), 0.9 more LLA (RD 0.90 [95% CI 0.10, 1.70]), 57.1 more genital infections (RD 57.08 [95% CI 53.45, 60.70]), and 7.1 fewer AKI events (RD −7.05 [95% CI −10.27, −3.83]) per 1,000 person-years. CONCLUSIONS Among older adults, those taking SGLT2i had similar MACE risk, decreased HHF risk, and increased risk of DKA, LLA, and genital infections versus those taking GLP-1RA.

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In our ageing society diabetes imposes a significant burden in terms of the numbers of people with the condition, diabetes‐related complications including disability, and health and social care expenditure. Older people with diabetes can represent some of the more complex and difficult challenges facing the clinician working in different settings, and the recognition that we have only a relatively small (but increasing) evidence base to guide us in diabetes management is a limitation of our current approaches. Nevertheless, in this review we attempt to explore what evidence there is to guide us in a comprehensive scheme of treatment for older adults, often in a high‐risk clinical state, in terms of glucose lowering, blood pressure and lipid management, frailty care and lifestyle interventions. We strive towards individualized care and make a call for action for more high‐quality research using different trial designs.