Insights from VERIFY: Early Combination Therapy Provides Better Glycaemic Durability Than a Stepwise Approach in
David Matthews1,2, Stefano Del Prato3, Viswanathan Mohan4
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK. david.matthews@ocdem.ox.ac.uk.
Abstract:
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.
Insights
Early combination therapy for type 2 diabetes, using vildagliptin and metformin, significantly improved long-term glycemic control compared to metformin alone. This approach delays treatment failure and enhances patient outcomes.
Area of Science:
- Endocrinology and Metabolism
- Pharmacology
- Clinical Medicine
Background:
- Type 2 diabetes management aims to prevent complications and mortality through glycemic control.
- Current stepwise treatment approaches often lead to delayed intensification and inadequate HbA1c control.
- Clinical inertia and late diagnosis negatively impact patient prognosis.
Purpose of the Study:
- To evaluate the efficacy of early combination therapy versus metformin monotherapy in type 2 diabetes.
- To assess the impact of early combination therapy on time to loss of glycemic control and secondary treatment failure.
- To explore a new paradigm for type 2 diabetes management beyond the traditional stepwise approach.
Main Methods:
- The multinational VERIFY study (NCT01528254) accrued 5-year data.
- Compared vildagliptin-metformin combination therapy against metformin monotherapy.
- Monitored glycated haemoglobin (HbA1c) levels and time to secondary treatment failure.
Main Results:
- Early combination therapy nearly doubled the time to loss of glycemic control.
- More than twice the number of patients achieved extended glycemic control with combination therapy.
- A significant delay in secondary treatment failure was observed in the combination therapy group.
Conclusions:
- Early combination therapy with vildagliptin-metformin offers a superior and sustained glycemic control trajectory compared to metformin alone.
- This approach represents a potential shift towards intensive early management for type 2 diabetes.
- Implementing early combination therapy requires early diagnosis and a change in clinical practice to improve long-term patient outcomes.
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