Swarna, Kavya S

Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and sodium–glucose cotransporter‐2 inhibitors (SGLT2is) have favorable cardiovascular outcomes compared with dipeptidyl peptidase‐4 inhibitors (DPP4is) and sulfonylureas in adults with type 2 diabetes and high cardiovascular risk. How these benefits vary across lower levels of cardiovascular risk is unknown. Methods We used nationwide claims data to emulate a comparative effectiveness trial and examine the heterogeneity of treatment effects of GLP‐1RAs, SGLT2is, DPP4is, and sulfonylureas on major adverse cardiovascular events (MACEs) among adults with type 2 diabetes and moderate cardiovascular risk (annualized MACE risk 1%–5%, estimated using the annualized claims‐based MACE estimator). Results Among 386 276 included adults with type 2 diabetes, 25.2% had baseline ACME–predicted MACE risk >1% to ≤2% (lower‐risk patients) and 13.3% had ACME–predicted risk >4% to ≤5% (higher‐risk patients). By year 3 of treatment, higher‐risk patients derived greater absolute benefit than lower‐risk patients when treated with GLP‐1RAs versus sulfonylureas (absolute reduction in the estimated rate of MACE of 3.1% in higher‐risk patients and 1.6% in lower‐risk patients), SGLT2is versus sulfonylureas (absolute reduction, 3.9% in higher‐risk patients and 1.3% in lower‐risk patients), and GLP‐1RAs versus DPP4is (absolute reduction, 1.6% in higher‐risk patients and 0.5% in lower‐risk patients). The relative benefits for MACE were also greater in higher‐risk than lower‐risk patients with SGLT2is versus DPP4is (hazard ratio [HR], 0.78 [95% CI, 0.70–0.87] in higher‐risk patients; HR, 0.99 [95% CI, 0.88–1.12] in lower‐risk patients). Conversely, the relative benefits of DPP4is and GLP‐1RAs versus sulfonylureas were greater in lower‐risk patients: HR 0.76 (95% CI, 0.71–0.81) in lower‐risk and HR 0.91 (95% CI, 0.97–0.96) in higher‐risk patients for DPP4is versus sulfonylureas; HR 0.67 (95% CI, 0.58–0.78) in lower‐risk and HR 0.80 (95% CI, 0.70–0.93) in higher‐risk patients for GLP‐1RAs versus sulfonylurea. Benefits of SGLT2is and GLP‐1RAs were comparable across all risk levels. Conclusions Cardiovascular benefits of SGLT2is and GLP‐1RAs exist across all levels of moderate cardiovascular risk, reinforcing the importance of choosing glucose‐lowering therapies that can prevent MACE in all people with type 2 diabetes.

ImportancePreventing diabetes complications requires monitoring and control of hyperglycemia and cardiovascular risk factors. Switching to high-deductible health plans (HDHPs) has been shown to hinder aspects of diabetes care; however, the association of HDHP enrollment with microvascular and macrovascular diabetes complications is unknown.ObjectiveTo examine the association between an employer-required switch to an HDHP and incident complications of diabetes.Design, Setting, and ParticipantsThis retrospective cohort study used deidentified administrative claims data for US adults with diabetes enrolled in employer-sponsored health plans between January 1, 2010, and December 31, 2019. Data analysis was performed from May 26, 2022, to January 2, 2024.ExposuresAdults with a baseline year of non-HDHP enrollment who had to switch to an HDHP because their employer offered no non-HDHP alternative in that year were compared with adults who were continuously enrolled in a non-HDHP.Main Outcomes and MeasuresMixed-effects logistic regression models examined the association between switching to an HDHP and, individually, the odds of myocardial infarction, stroke, hospitalization for heart failure, lower-extremity complication, end-stage kidney disease, proliferative retinopathy, treatment for retinopathy, and blindness. Models were adjusted for demographics, comorbidities, and medications, with inverse propensity score weighting used to account for potential selection bias.ResultsThe study included 42 326 adults who switched to an HDHP (mean [SD] age, 52 [10] years; 19 752 [46.7%] female) and 202 729 adults who did not switch (mean [SD] age, 53 [10] years; 89 828 [44.3%] female). Those who switched to an HDHP had greater odds of experiencing all diabetes complications (odds ratio [OR], 1.11; 95% CI, 1.06-1.16 for myocardial infarction; OR, 1.15; 95% CI, 1.09-1.21 for stroke; OR, 1.35; 95% CI, 1.30-1.41 for hospitalization for heart failure; OR, 2.53; 95% CI, 2.38-2.70 for end-stage kidney disease; OR, 2.23; 95% CI, 2.17-2.29 for lower-extremity complication; OR, 1.17; 95% CI, 1.13-1.21 for proliferative retinopathy; OR, 2.35; 95% CI, 2.18-2.54 for blindness; and OR, 2.28; 95% CI, 2.15-2.41 for retinopathy treatment).Conclusions and RelevanceThis study found that an employer-driven switch to an HDHP was associated with increased odds of experiencing all diabetes complications. These findings reinforce the potential harm associated with HDHPs for people with diabetes and the importance of affordable and accessible chronic disease management, which is hindered by high out-of-pocket costs incurred by HDHPs.