Data Sheet 2_Early insulin combined with metformin therapy and long-term risks of cardiovascular disease, kidney disease, and cancer in newly diagnosed type 2 diabetes: a real-world cohort study in China.pdf

The combination group required at least 14 days of overlapping insulin and metformin use. L1-regularized propensity score matching and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) over up to 1,500 days. Sensitivity analyses used a 180-day outcome-exclusion window.</p>Results<p>Compared with metformin monotherapy, early insulin combined with metformin therapy was associated with a lower hazard of stroke (HR 0.88, 95% CI 0.78–0.99) and higher hazards of heart failure (HR 1.18, 95% CI 1.02–1.36), chronic kidney disease (HR 1.37, 95% CI 1.03–1.83), and cancer (HR 1.37, 95% CI 1.14–1.66).

Exploratory subgroup estimates varied by age and sex; no formal interaction tests were performed. Results were broadly consistent in sensitivity analyses.</p>Conclusion<p>Early insulin combined with metformin therapy and metformin monotherapy showed different longitudinal associations with the four outcomes. These findings should be interpreted in light of residual confounding by baseline disease severity and treatment indication and may inform risk monitoring in routine care.</p>