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OBJECTIVE To examine kidney disease outcomes associated with dipeptidyl peptidase 4 inhibitors (DPP-4i). RESEARCH DESIGN AND METHODS In this target trial emulation, claims data from enrollees in commercial, Medicare Advantage, and traditional Medicare health plans were used to identify adults ≥21 years old with type 2 diabetes, with moderate cardiovascular risk, and without stage 3 or worse chronic kidney disease (CKD) initiating alogliptin, linagliptin, saxagliptin, or sitagliptin between 2014 and 2021. The primary outcome was a composite of incident CKD stages 3–5, kidney failure, or kidney replacement therapy. Random treatment assignment was emulated using propensity scores, estimated using the super learner ensemble method and incorporated as inverse probability of treatment weights into proportional hazards models. RESULTS The weighted study cohort included 3,026 individuals starting alogliptin, 38,213 starting linagliptin, 14,934 starting saxagliptin, and 115,091 starting sitagliptin. One year after treatment initiation, the primary outcome occurred in 1.4%, 2.7%, 2.2%, and 2.4% of patients initiating alogliptin, linagliptin, saxagliptin, and sitagliptin, respectively, increasing to 3.2%, 6.2%, 5.0%, and 5.4%, respectively, at 3 years. Alogliptin was associated with lower risk of stage 3 or worse CKD than linagliptin (hazard ratio [HR] 0.50; 95% CI 0.37–0.69), saxagliptin (HR 0.63; 95% CI 0.45–0.86), and sitagliptin (HR 0.58; 95% CI 0.42–0.79), while saxagliptin was associated with lower risk than linagliptin (HR 0.80; 95% CI 0.73–0.87). Conversely, linagliptin was associated with higher risk than sitagliptin (HR 1.15, 95% CI 1.10–1.21). CONCLUSIONS Alogliptin was associated with lower risk of moderate-to-severe kidney disease than other DPP-4i, while linagliptin was associated with higher risk. Limitations include lack of laboratory data and potential unmeasured confounding.

1587 Background: Rehabilitation services (physical medicine and rehabilitation [PM&R], physical therapy [PT], occupational therapy [OT], and speech-language pathology [SLP]) improve physical function, symptom burden, and quality of life for cancer survivors, yet utilization remains low due to persistent barriers. The collaborative care model–based Enhanced Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) pragmatic trial improved symptom burden and palliative care utilization. Using post hoc exploratory analyses of population-level trial data, we evaluated whether this EHR-facilitated approach also increased rehabilitation service use. Methods: E2C2 was conducted across Mayo Clinic Midwest medical oncology practices using an unblinded, stepped-wedge, cluster-randomized cohort design. The EHR-embedded intervention targeted SPPADE symptoms (sleep interference, pain, impaired physical function, anxiety, depression, and fatigue). Symptoms and physical function were assessed using 11-point numerical rating scales linked to oncology encounters. Patients received self-management materials for moderate symptoms (4–6/10) and care manager support for severe symptoms (7–10/10). All outpatient rehabilitation encounters across the Mayo Clinic Enterprise were abstracted. Mixed-effects Poisson models estimated intervention effects on rehabilitation visits during the first 365 days of exposure. Results: Between March 28, 2019, and January 31, 2023, 50,207 patients were enrolled. Intervention and control conditions included 31,719 and 28,938 patients, respectively, with 10,450 contributing data to both periods. Cross-sectionally, 25% of participants reported moderate and 9% severe physical function impairment. Of 91,220 rehabilitation encounters scheduled, 57,669 (63.3%) were completed. Completed encounters were predominantly PT (68.3%), followed by OT (16.4%), physician visits (9.4%), and SLP (4.2%). The intervention was associated with a more than fourfold increase in completed rehabilitation encounters during the six weeks following index symptom assessment (adjusted mean 2.22 [95% CI, 0.14–4.29] vs 0.54 [0.40–0.68]; incidence rate ratio 4.11 [1.43–11.82]; P =0.009). Scheduled encounters also favored the intervention but did not reach statistical significance. Conclusions: An EHR-embedded symptom surveillance intervention increased short-term rehabilitation service completion, but overall utilization remained low relative to the prevalence of physical function impairment, highlighting the need for system-level strategies to translate symptom identification into sustained rehabilitation engagement.

1584 Background: Decades of evidence demonstrate that patients across the cancer continuum may benefit from validated rehabilitation services, yet delivery remains inconsistent. Prior reports of underuse have largely relied on small, single-site cohorts and have lacked population-level estimates of service need, referral, and visit completion, contributing to the assumption that provider reluctance to refer is a primary driver. Using post hoc exploratory analyses of population-level trial data, we evaluated patient- and system-level factors associated with non-use of rehabilitation services. Methods: This secondary analysis used data from the Enhanced Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) pragmatic trial, an unblinded, stepped-wedge, cluster-randomized cohort study comparing an EHR-embedded symptom surveillance and management system with usual care. All patients receiving care in Mayo Clinic Midwest medical oncology practices were enrolled regardless of cancer stage or phase. Symptoms and physical function were assessed using 11-point numerical rating scales linked to oncology encounters. Sociodemographic and clinical characteristics and all outpatient rehabilitation encounters across the Mayo Clinic Enterprise were extracted from the EHR. Rates and types of completed, canceled, and no-show rehabilitation encounters were examined. Results: Between March 28, 2019, and January 31, 2023, 50,207 patients were enrolled; 34% reported moderate or severe physical function impairment during follow-up. Despite this, only 8,818 patients (17.6%) completed at least one rehabilitation encounter. Of 91,220 encounters scheduled, 57,669 (63.3%) were completed (mean 6.5; median 3 per participant), leaving a substantial proportion canceled or no-showed (n=33,523, 36.7%). Completed encounters were predominantly physical therapy (68.3%), with fewer occupational therapy (16.4%), physician (9.4%), and speech therapy (4.2%) visits. Encounters were concentrated among patients with breast, hematologic, gastrointestinal, and genitourinary cancers. Completion was more likely among patients who were older, female, partnered, retired, and federally insured, whereas cancellations and no-shows were more common among younger, racial or ethnic minority, urban, unpartnered, employed, college-educated, and commercially insured patients (all P <0.001). Virtual visits and encounters in community (vs academic) settings were more likely to be completed (all P <0.001). Conclusions: A substantial gap persists between cancer survivors’ rehabilitation needs and service receipt, varying by cancer type and sociodemographic factors. High cancellation and no-show rates suggest that underuse extends beyond referral and underscore the need for redesigned, more accessible rehabilitation delivery models.

Introduction To assess the within-class variation in kidney outcomes following initiation of sulfonylurea therapy. Research design and methods We used claims data of enrollees in commercial, Medicare Advantage, and traditional Medicare health plans between 2014 and 2021 to emulate a target trial including adults ≥21 years with type 2 diabetes at moderate cardiovascular risk to compare initiation of glimepiride, glipizide, or glyburide on the incidence of chronic kidney disease (CKD) stage 3 or worse, including initiation of kidney replacement therapy (primary outcome); secondary outcomes examined incident CKD stages 3-4, kidney failure (including kidney replacement therapy), all-cause mortality, and hypoglycemia requiring emergency department or hospital care. Random treatment assignment was emulated using propensity scores, estimated using the super learner ensemble method, and incorporated as inverse probability of treatment weights into proportional hazards models. Results The weighted study cohort included 295 092 individuals starting glimepiride (n=134 926), glipizide (n=145 984), and glyburide (n=14 182). One year after treatment initiation, stage 3 or worse CKD developed in 2.1% of patients in the glimepiride group, 2.2% in the glipizide group, and 1.8% in the glyburide group. Glyburide was associated with a lower risk of kidney complications compared with both glimepiride (HR 0.84, 95% CI 0.76 to 0.92) and glipizide (HR 0.81, 95% CI 0.73 to 0.89), despite a higher risk of severe hypoglycemia (HR 1.47, 95% CI 1.27 to 1.71 vs glipizide and HR 1.22, 95% CI 1.05 to 1.42 vs glimepiride). In contrast, the risk of kidney complications was modestly increased with glipizide compared with glimepiride use (HR 1.04, 95% CI 1.00 to 1.07). Conclusions Glyburide was associated with a modestly lower risk of kidney complications, despite a higher risk of hypoglycemia, while glipizide was associated with a higher risk of kidney complications. These hypothesis-generating findings suggest important within-class differences that warrant consideration in clinical decision-making and future research. Despite rigorous prespecified causal inference analytic methods, the risk of unmeasured confounding and bias by indication with the use of observational data remains. Trial registration number NCT05214573 .

Background SGLT2 (sodium‐glucose cotransporter 2) inhibitors reduce major adverse cardiovascular events (MACE) in type 2 diabetes. However, no direct comparison of individual SGLT2 inhibitor drugs has been conducted, particularly among adults with moderate cardiovascular risk who comprise most people with type 2 diabetes. Methods We used data for commercial, Medicare Advantage, and Medicare fee‐for‐service beneficiaries to emulate a target trial of adults (≥21 years) with type 2 diabetes and moderate cardiovascular risk who started canagliflozin, dapagliflozin, or empagliflozin between 2015 and 2020. We estimated propensity scores using the super learner ensemble method and incorporated them as inverse probability of treatment weights into Cox models, estimating risk of MACE, expanded MACE, and hyperglycemic and hypoglycemic crises through December 31, 2022. Results The weighted cohort, balanced on all baseline covariates, included 137 232 patients (mean age 65.7 years [SD, 8.1], 75.3% non‐Hispanic White, 57.0% male, 81.9% on metformin, 11.4% on glucagon‐like peptide‐1 receptor agonists) starting canagliflozin (N=42 877), dapagliflozin (N=17 871), or empagliflozin (N=7648). The risk of MACE was lower among patients starting empagliflozin versus canagliflozin (hazard ratio [HR], 0.92 [95% CI, 0.87–0.97]), driven by reduced risk of all‐cause mortality (HR, 0.86 [95% CI, 0.80–0.94]). There was no difference in MACE between empagliflozin versus dapagliflozin or dapagliflozin versus canagliflozin therapy. There was no difference in remaining outcomes between the three drugs. Conclusions The 3 most used SGLT2 inhibitor medications demonstrate similar effectiveness on cardiovascular outcomes among patients with type 2 diabetes at moderate cardiovascular risk, with differences between these drugs small in magnitude. Clinicians and health systems should prioritize enhancing access to these cardioprotective therapies.

Abstract Background Immigrants to the United States often face challenges from limited healthcare access and less healthy environments which contribute to rising obesity and cardiovascular risk. Purpose To assess the feasibility and effectiveness of a community-based social network intervention for cardiovascular risk reduction among Hispanic and Somali adults. Methods A social network-informed, community-based participatory research-derived health promotion intervention was delivered by Hispanic and Somali lay health promoters (HPs) to members of their social networks over 1 year (12 biweekly sessions in months 0-6; 12 biweekly check-ins in months 7-12). Using a closed-cohort stepped wedge cluster randomized design, social networks were randomly assigned to receive the intervention immediately or after a delay of 1 year. Measurements at baseline, 6 months, and 12 months were derived from 6 of the American Heart Association’s “Life’s Simple 7”: BMI, blood pressure, fasting glucose, cholesterol, physical activity and dietary quality (range 0-12, with higher values indicating lower cardiovascular risk). Waist circumference and proportion of participants who achieved &gt;5% body weight loss were also assessed. Results Four hundred seventy-five participants were enrolled among 51 HPs (29 Hispanic; 22 Somali). There was a statistically significant improvement in cardiovascular risk in the intervention group (n = 246) compared with controls (n = 229) at 6 months (0.4 [1.8] vs. −0.1 [1.7]; P = .03) that was not sustained at 12 months (0.5 [1.9] vs. 0.3 [1.8]; P = .38). There was a statistically significant higher proportion of participants who lost &gt;5% of body weight in the intervention group compared with controls at 12 months (37% [15] vs. 18% [7.9]; P = .02). Reductions in weight and waist circumference in the intervention group compared with controls did not achieve statistical significance. Conclusion A social network intervention, delivered by lay HPs was feasible and resulted in a modest improvement of cardiovascular risk and clinically significant weight loss. Clinical Trial Identification Number NCT05136339.

Abstract Context Osteoanabolic therapy for osteoporosis should be followed by antiresorptive treatment (“consolidation”) to preserve bone mass. Although osteoanabolic therapy is increasingly endorsed for primary fracture prevention, real-world implementation of consolidation remains unknown. Objective To assess patterns and predictors of timely consolidation after osteoanabolic therapy for primary fracture prevention. Methods We conducted a retrospective cohort study using US commercial, Medicare Advantage, and traditional Medicare claims data. Adults aged ≥50 years who initiated romosozumab, teriparatide, or abaloparatide between 2011 and 2022 were included. The primary outcome was timely consolidation, defined as initiation of an antiresorptive medication within 3 months after osteoanabolic therapy. Secondary outcomes included delayed consolidation (initiation &gt;3 months after completion), osteoanabolic restart following a treatment gap, and no consolidation therapy. We further distinguished participants who completed the full osteoanabolic course, defined as ≥12 months for romosozumab and ≥18 months for teriparatide or abaloparatide. Multivariable logistic regression models were used to identify predictors of consolidation patterns. Results Among 15 389 patients (mean age 70.6 years; 89% women; 85% White), 30% completed osteoanabolic therapy (median, 12.9 months for romosozumab; 23.4 months for teriparatide/abaloparatide). Overall, 25% had timely consolidation, 24% delayed consolidation, 12% restarted osteoanabolics, and 40% had no consolidation; only 12% completed therapy with timely consolidation. Timely consolidation was more likely with endocrinology (OR 1.31; 95% CI, 1.17-1.48) or rheumatology (OR 1.45; 1.30-1.62) vs primary care, and less likely among patients aged 50-64 years (OR 0.67; 0.58-0.77) vs 65-74, those enrolled in Medicare Advantage (OR 0.85; 0.74-0.98) vs traditional Medicare, or those recently hospitalized (OR 0.88; 0.80-0.97). Odds increased over time (OR 4.27; 3.63-5.05 for 2021 vs 2011 starts). Conclusion Only 1 in 4 patients received timely consolidation therapy after osteoanabolic treatment, and 1 in 8 completed the full sequence. Strategies to improve consolidation in primary fracture prevention are needed.

Introduction To examine within-class sulfonylurea safety, we compared risks of major adverse cardiovascular events (MACE) and severe hypoglycemia among adults with type 2 diabetes (T2D) and moderate cardiovascular risk following sulfonylurea initiation. Research design and methods We conducted a target trial emulation including adults ≥21 years old with T2D and moderate cardiovascular risk who initiated glimepiride, glipizide or glyburide between 2014 and 2021, using claims data from Optum Labs Data Warehouse and the Medicare fee-for-service 100% sample. Study outcomes were MACE (primary), expanded MACE and its components and emergency department or hospital encounters for hypoglycemia, ascertained during follow-up through 2022. Inverse probability of treatment weighting (IPTW) was applied using propensity scores estimated using the super learner ensemble, and outcomes were examined using IPTW Cox proportional hazards models. Results The weighted study cohort comprised 314 699 patients (mean age 66.9 years, 52.0% men, 76.6% non-Hispanic white). At 1 year, MACE was experienced by 2.5%, 2.7% and 2.8% of patients starting glimepiride, glipizide and glyburide, respectively. Compared with glimepiride, glyburide and glipizide were associated with higher risk of MACE (HR 1.10, 95% CI 1.05 to 1.16 for glyburide; HR 1.05, 95% CI 1.03 to 1.07 for glipizide). At 1 year, severe hypoglycemia was experienced by 0.3%, 0.3% and 0.4% of patients starting glimepiride, glipizide and glyburide, respectively. Glyburide was associated with a greater risk of severe hypoglycemia compared with glipizide (HR 1.43, 95% CI 1.23 to 1.65), while glipizide was associated with a lower risk compared with glimepiride (HR 0.82, 95% CI 0.77 to 0.87). Conclusions Among adults with T2D and moderate cardiovascular risk, glimepiride was associated with lowest risk of MACE and glipizide with lowest risk of severe hypoglycemia. These results can help inform treatment selection if sulfonylureas are used for glucose-lowering.

This cohort study examines the clinical implementation of timely consolidation with antiresorptive therapy to preserve bone mineral density gains and reduce fracture risk.

This economic evaluation estimates the implementation costs and cost per additional patient receiving the vaccine associated with each of the intervention strategies for increasing rates of human papillomavirus (HPV) vaccination in primary care practices.