IDF21-0199 Early combination therapy improves glycaemic control in newly diagnosed T2DM: VERIFY sub-regional analysis (East Asia)

Abstract

Background: Incidence of type 2 diabetes mellitus (T2DM) is high in Asia. The VERIFY study (NCT01528254) with a multi-ethnic population and newly diagnosed T2DM showed that early combination (EC) treatment strategy (vildagliptin plus metformin) provides long-term clinical benefits when compared to current standard-of-care (metformin monotherapy followed by sequential intensification). Aim: Here we explored the long-term outcomes of EC treatment strategy in patients enrolled in the VERIFY study from East Asia (Taiwan, Hong Kong and South Korea). Method: Patients with newly diagnosed T2DM (≤2 years) with mild hyperglycaemia (HbA1c 6.5–7.5%; [48–58 mmol/mol]) were randomised 1:1 to receive either the EC treatment or initial metformin monotherapy. The primary endpoint was time to confirmed initial treatment failure (TF) defined as HbA1c ≥7.0% at two consecutive scheduled visits after randomisation. If the initial treatment did not maintain HbA1c levels <7.0%, patients in the monotherapy group received vildagliptin. The time to secondary TF was met when patients in both groups were receiving and failing on the combination therapy. Results: A total of 89 eligible patients (18–70 years, BMI 22–40 kg/m2) enrolled in East Asia were randomly assigned to either the EC group (n = 48) or the metformin monotherapy group (n = 41). Among them 38 (79.2%) patients receiving the EC and 36 (87.8%) receiving the monotherapy completed the study (60 months). Majority of the patients were aged <60 years (82%) and 46.1% were females. The incidence of initial TF was 48.8% in the monotherapy group and 21.7% in the EC group. The median (IQR) time to initial TF was not evaluable (NE) within the study duration (60.09–NE) for EC and 60.09 (32.95–NE) months for metformin monotherapy. EC treatment significantly reduced the relative risk (RR) of time to initial TF among East Asian participants by 62% vs. monotherapy (HR [95% CI]: 0.38 [0.18, 0.80]; p = 0.0117). Compared to monotherapy, patients in the EC group showed a trend towards a reduced risk of secondary TF (HR [95% CI]: 0.71 [0.25, 2.04], p = 0.5223), albeit not reaching statistical significance. There was also a consistently lower HbA1c level seen over time with the EC treatment approach vs. monotherapy, with a greater proportion of participants in the EC group with HbA1c cut‑off values of <7%, <6.5% and <6%. Both treatment approaches were well tolerated with no unexpected safety concerns. Only one patient, allocated to the monotherapy group, discontinued treatment due to an adverse event. No hypoglycaemic events were reported in East Asia. Discussion: Consistent with the global population, the early intervention strategy with vildagliptin plus metformin combination provided better glycaemic control compared to standard‑of‑care metformin monotherapy within this sub-region. Also, these clinical benefits were achieved without an increased risk of adverse events or hypoglycaemia in East Asian patients with newly diagnosed T2DM.