General Medicine · Medical Literature
Audio Highlights July 2, 2026
Abstract
Listen to the JAMA Editor’s Summary for an overview and discussion of the important articles appearing in JAMA.
Clinical relevance
The JAMA Audio Highlights of July 2, 2026 serves as an editorial overview of the issue's landmark trials rather than a primary research article; accordingly, this summary is derived from the two highest-impact primary studies featured: the TRACK randomized trial (low-dose rivaroxaban in advanced CKD) and the ACHIEVE-5 phase 3 trial (oral orforglipron added to insulin glargine in type 2 diabetes). Both trials address critical evidence gaps in populations — advanced CKD and insulin-treated type 2 diabetes — that have historically been underrepresented in cardiovascular and metabolic outcome trials. Clinicians managing patients with CKD stages 4–5 or dialysis, and those with insulin-dependent type 2 diabetes failing basal insulin, should urgently incorporate these findings into treatment decision frameworks.
Key findings
TRACK Trial (Badve SV et al., JAMA 2026; doi:10.1001/jama.2026.9379): 1. Primary composite outcome (cardiovascular death, nonfatal MI, stroke, or PAD event) occurred in 23% of the rivaroxaban group vs. 21% of placebo (13.0 vs. 11.8 events/100 person-years; HR 1.09, 95% CI 0.87–1.36), demonstrating no significant cardiovascular benefit with rivaroxaban 2.5 mg twice daily in 1,458 patients with CKD stage 4/5 or dialysis. 2. Major bleeding occurred in 8.8% of rivaroxaban patients vs. 6.0% of placebo patients (HR 1.51, 95% CI 1.02–2.22), representing a statistically significant increase in harm. 3. Net clinical benefit (composite of CV events + fatal/critical bleeding) was comparable between arms (24.2% vs. 21.3%; HR 1.14, 95% CI 0.92–1.41), confirming an unfavorable risk-benefit profile. 4. VTE events were numerically fewer with rivaroxaban (0.6% vs. 1.9%; aHR 0.29, 95% CI 0.09–0.87), but this did not offset the excess bleeding risk. ACHIEVE-5 Trial (Giorgino F et al., JAMA 2026; doi:10.1001/jama.2026.9512): 5. All three doses of oral orforglipron (3 mg, 12 mg, 36 mg once daily) were superior to placebo in reducing HbA1c at 40 weeks in 546 adults with type 2 diabetes on insulin glargine (estimated treatment differences: −0.78% [95% CI −1.02% to −0.55%], −1.08% [95% CI −1.33% to −0.83%], and −1.03% [95% CI −1.28% to −0.77%], respectively; P < .001 for all doses). 6. Mean body weight decreased by 2.6%, 4.8%, and 5.4% with orforglipron 3 mg, 12 mg, and 36 mg, respectively, vs. a 0.2% weight increase with placebo (P < .001 for all); orforglipron did not increase the risk of clinically significant hypoglycemia vs. placebo, and 43%–60% of orforglipron-treated patients achieved HbA1c ≤6.5% vs. 12% on placebo.
Practice implications
Based on the TRACK trial, low-dose rivaroxaban 2.5 mg twice daily should NOT be used for cardiovascular risk reduction in patients with CKD stage 4/5 or dialysis-dependent kidney failure, as it confers no MACE benefit while significantly increasing major bleeding risk (NNH for major bleeding approximately 36); clinicians should not extrapolate anticoagulation benefits observed in the COMPASS trial to this population. Based on ACHIEVE-5, oral orforglipron (FDA-approved as Foundayo) is a viable intensification strategy for adults with type 2 diabetes inadequately controlled on basal insulin glargine: the 12 mg or 36 mg once-daily dose should be considered as an oral GLP-1 receptor agonist add-on to avoid injectable intensification, achieve meaningful HbA1c reduction (up to −1.88 percentage points), promote weight loss (up to −5.4%), and reduce insulin dose escalation without increasing hypoglycemia risk, particularly in patients who decline or are unable to use injectable GLP-1 agents.