Diabetes Ther. 2020 Sep 25. doi: 10.1007/s13300-020-00926-7. Online ahead of print.
The treatment aims for type 2 diabetes are to prevent complications and premature mortality, and improve quality of life. Glycaemic control is central to these aims; clinical guidelines have sought to achieve this with a stepwise approach starting with lifestyle measures and metformin, adding further medications once glycated haemoglobin (HbA1c) levels rise above a predefined threshold. However, treatment intensification can be delayed when HbA1c levels increase, and HbA1c levels become inadequately controlled in many patients. Clinical inertia can result in sustained elevated levels of HbA1c; when combined with a late diagnosis, this negatively impacts patients' prognosis. Early combination therapy using medications with complementary modes of action could achieve optimal glycaemic targets and alter the course of the disease more than metformin alone. The multinational VERIFY study (clinicaltrials.gov NCT01528254) provided evidence accrued over 5 years, demonstrating the potential of early combination therapy: time to loss of glycaemic control was nearly doubled, and more than twice the number of patients experienced extended glycaemic control, with a vildagliptin-metformin combination therapy versus metformin alone. The study also showed a delay in secondary treatment failure in patients receiving the combination. Early combination therapy therefore offers a different trajectory to the stepwise approach. Translating these findings into clinical practice will require early detection and diagnosis of type 2 diabetes plus a shift in disease management. Nonetheless, the potential benefits of sustained and continuous disease control that early combination therapy offers represent the start of a new era in early diagnosis and intensive management, to achieve the treatment aims of type 2 diabetes.