After 4 years of follow-up, 12,295 (24.8%) patients with DM had increasing frail severity over time (Table 2), among whom 24.7%, 26.0%, 22.0%, and 29.5% of the no GLD, oGLD monotherapy, oGLD combination, and the insulin user group participants developed the outcome of interest, respectively (Fig. 2A). The gene discussed is INS; the disease is diabetes mellitus.