efficacy of initial TCT in drug-naïve patients with T2D

At the 59^th Annual European Association for the Study of Diabetes (EASD) 2023 meeting, a study by Kim and colleagues investigating the efficacy and tolerability of an initial triple combination therapy (TCT) with metformin, dapagliflozin, and saxagliptin compared with conventional stepwise add-on therapy in drug-naïve patients with type 2 diabetes (T2D) was presented.

The study authors noted that early combination therapy is recommended in T2D patients with inadequately controlled hyperglycemia to avoid treatment failure and clinical inertia. GlobalData forecasts that as a growing number of combination therapies are entering the T2D market, they will be increasingly utilized by physicians looking to address glycemic control in addition to cardiorenal comorbidities in their patients.

This study was a multicenter, randomized, 104-week, open-label trial conducted across nine medical centers in South Korea. Eligible patients were ages 18 years and older, inadequately controlled (haemoglobin A1c [HbA1c] ≥8.0% to ≤11%), and drug-naïve with recent onset T2D. They were randomly assigned to TCT (1,000mg metformin, 10mg dapagliflozin, and 5mg saxagliptin) once daily or conventional stepwise therapy (CST).

CST was started with metformin followed by glimiperide and sitagliptin sequentially. The primary outcome for the study was the proportion of patients that achieved HbA1c <6.5% without hypoglycemia, weight gain ≥5%, and discontinuation due to adverse events at week 104. There were 105 eligible patients randomly assigned to either the TCT or CST groups, and 89.6% of participants completed the study and treatment.

The primary outcome was achieved on 42.5% TCT and 17.5% CST (p=0.015), and the proportion of patients achieving HbA1c <6.5% at week 104 was 50% for the TCT group and 45% for the CST group. Hypoglycemia, weight gain >5%, or discontinuation due to adverse events occurred in 14.9% of the TCT group and 59.2% of the CST group.

The study authors concluded that initial combination therapy with metformin + dapagliflozin + saxagliptin effectively lowered HbA1c with conventional stepwise treatment in recent onset T2D. Key opinion leaders (KOLs) interviewed by GlobalData reported positive long-term outcomes for dual combination therapies such as Synjardy (empagliflozin and metformin), and have stated that they are keen to prescribe the triple combination therapy Trijardy (empagliflozin + linagliptin + metformin).

Combinations that are likely to enter the T2D market in the near future include GLP-1 + insulin therapies such as Novo Nordisk’s Icosema, and there will likely be further generic combinations of metformin + sodium-glucose co-transporter-2 inhibitors (SGLT-2Is) + dipeptidyl peptidase 4 inhibitors (DPP-4Is).