Early use of DPP-4 inhibitors delays insulin initiation in Chinese T2D patients

Early dipeptidyl peptidase 4 (DPP-4) inhibitor intensification delays insulin initiation in Chinese patients with type 2 diabetes (T2D), a cohort study in Hong Kong has shown.

“The legacy effect of early glycaemic control on long-term complications has been demonstrated in the United Kingdom Prospective Diabetes Study [UKPDS],” wrote the researchers. “Although sodium-glucose cotransporter 2 [SGLT2] inhibitors conferred cardiorenal protective effects in patients with long disease duration, complications and/or multiple risk factors, the majority of T2D patients did not have cardiorenal disease. For these patients, optimal glycaemic control remained an important strategy for long-term organ protection.”

In a prospective, territory-wide cohort study, data of patients with T2D on DPP-4 inhibitors (n=1,816; mean age, 54.41 years; male, 60.7 percent; mean diabetes duration, 2.80 years; mean HbA1c, 8.35 percent) at diabetes duration <2 years (early intensification group) and 3–5 years (late intensification group) were retrieved from the Hong Kong Diabetes Surveillance Database and matched 1:1 using propensity score matching. Patients with disease duration >5 years were excluded. At DPP-4 inhibitor initiation, 92.4 percent of patients were treated with metformin and 71.9 percent were on sulphonylureas. [Diabetes Metab Res Rev 2023;doi:10.1002/dmrr.3711]

At 8 years, insulin was required in 49.9 percent of patients in the late DPP-4 inhibitor intensification group vs 35.8 percent of those in the early DPP-4 inhibitor intensification group, indicating a significantly lower risk of insulin initiation with early DPP-4 inhibitor intensification (hazard ratio [HR], 0.71; 95 percent confidence interval [CI], 0.58–0.86; p=0.00053).

The trajectories of mean HbA1c of the two groups separated since month 6 (p<0.05). The legacy effect of early intensification became apparent at year 1 (mean HbA1c, 7.62 percent vs 7.88 percent; p=0.001) and persisted for 6 years (mean HbA1c, 7.69 percent vs 8.21 percent; p=0.001). “In our study, the between-group HbA1c difference of 0.52 percent at 6 years was clinically meaningful, given the legacy effect of early glycaemic control on long-term complications as demonstrated in UKPDS,” noted the researchers.

“Conceptually, early attainment of normal glycaemia will reduce glucose exposure, glycaemic deterioration and progressive treatment escalation with increasingly complex regimens [eg, insulin],”

wrote the researchers. They therefore examined HbA1c variability score (HVS), defined as the percentage of HbA1c varying by ≥0.5 percent vs values in the preceding visit. Low HVS (<50 percent) was associated with a significantly lower rate of insulin requirement at 8 years (28.1 percent vs 60.8 percent; HR, 0.40; 95 percent CI, 0.33–0.50) vs high HVS (≥50 percent). The low HVS group with early DPP-4 inhibitor intensification showed a 70 percent risk reduction in insulin initiation at 8 years (23.5 percent vs 64.2 percent; HR, 0.30; 95 percent CI, 0.22–0.40; pinteraction=0.013) vs the high HVS group with late DPP-4 inhibitor intensification.

“Our results indicated that early DPP-4 inhibitor intensification within 2 years of T2D diagnosis could delay insulin initiation, which is partially explained by reduced glycaemic variability,” the researchers concluded. “Compared with other oral glucose‐lowering drugs, DPP-4 inhibitor intensification resulted in less glycaemic variability and a slower rate of decline in beta-cell function. This is especially relevant during the early stage of diabetes, when beta-cell function might be preserved,” they added.