Cardiorenal outcomes of weight loss interventions in people with CKD and type 2 diabetes.

BACKGROUND AND HYPOTHESIS: In patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), there remains a paucity of data from large high-quality real-world studies on the efficacy of weight-lowering interventions, including the glucagon-like peptide-1 based therapies semaglutide and tirzepatide, as well as bariatric surgery (BS). This retrospective cohort study evaluates these interventions on cardiorenal outcomes and mortality using health records from TriNetX US Collaborative Network. METHODS: Three cohorts with T2DM and CKD living with overweight or obesity, prescribed semaglutide or tirzepatide, or with a BS procedure were propensity-score matched with a cohort receiving DPP4 inhibitors (DPP4i, weight-neutral control). We investigated the hazard ratio (HR) of: (a) end-stage renal disease (ESRD); (b) myocardial infarction (MI); (c) stroke; and (d) all-cause mortality. RESULTS: Cohorts included 17,749 (semaglutide, age 64.1±10.9, 57.4% female), 4,211 (tirzepatide, 63.7±10.8, 58.1%) and 2,603 (BS, 56.1±11.2, 74.1%) patients. Compared to DPP4i, semaglutide reduced the risk of ESRD (0.78 (0.71 to 0.85)), while tirzepatide showed a reduction of 42% (0.0.58, 0.45 to 0.75). BS lowered ESRD risk (0.79, 0.67 to 0.92). Semaglutide reduced MI (0.80, 0.72 to 0.88) and stroke (0.85, 0.77 to 0.95) risk, while tirzepatide lowered MI and stroke by 24%. BS was associated with reduced MI (0.45, 0.35 to 0.58) and stroke (0.57, 0.44 to 0.74) risk. All-cause mortality risk was reduced by semaglutide (0.64, 0.59 to 0.70), tirzepatide (0.47, 0.35 to 0.63), and BS (0.68, 0.57 to 0.81). CONCLUSIONS: Using a real-world dataset, semaglutide, tirzepatide and BS, interventions shown to elicit weight loss and improve glycaemic control, have a myriad of benefits on cardio-renal outcomes and mortality, supporting their use as disease-modifying therapy options in T2DM and CKD.