What is the name of the trial that compared triple agent therapy for diabetes to standard of care treatment as per American Diabetes Association (ADA) guidelines?

TRIMASTER Trial Compared Triple Agent Therapy for Diabetes to Standard ADA Care

The TRIMASTER trial is the study that compared triple agent therapy for diabetes to standard of care treatment as per American Diabetes Association (ADA) guidelines.

Background on Triple Therapy Approach

The concept of triple therapy in diabetes management has evolved as guidelines recognize that diabetes is a progressive disease with multiple underlying pathophysiological defects. According to ADA guidelines, triple therapy may be necessary when dual therapy fails to achieve glycemic targets 1.

Triple therapy typically involves:

• Targeting multiple pathophysiological defects simultaneously
• Combining agents with complementary mechanisms of action
• Aiming to achieve better glycemic control without increasing side effects

Evidence Supporting Triple Therapy

The ADA Standards of Medical Care in Diabetes outlines an algorithmic approach to diabetes management that includes consideration of triple therapy when:

• Dual therapy does not achieve or maintain A1C goals after approximately 3 months 1
• Initial A1C is very high (≥9.0%) 1
• Patient has established cardiovascular disease requiring specific agent combinations 1

When implementing triple therapy, the ADA recommends using agents with complementary mechanisms of action to target the three main metabolic abnormalities of type 2 diabetes 1:

1. Defect in insulin secretion (targeted by sulfonylureas or glinides)
2. Increased hepatic glucose production (targeted by metformin)
3. Reduced insulin-mediated glucose uptake (targeted by thiazolidinediones)

Clinical Trial Evidence

Several clinical trials have evaluated triple therapy approaches:

• The Initial Triple Study compared initial triple combination of metformin, sitagliptin, and lobeglitazone with conventional stepwise therapy using sulfonylurea and metformin in drug-naïve patients 2
• Studies have shown that triple therapy using insulin, metformin, and thiazolidinedione can result in improved glycemic control without weight gain 3
• The combined effect of triple therapy with rosiglitazone, metformin, and insulin aspart demonstrated significant improvement in glucose metabolism in obese type 2 diabetic subjects 4

Key Considerations When Implementing Triple Therapy

When considering triple therapy, the ADA guidelines emphasize:

• Patient-centered approach to guide pharmacologic choices 1
• Consideration of efficacy, hypoglycemia risk, cardiovascular effects, impact on weight, side effects, renal effects, delivery method, cost, and patient preferences 1
• Regular monitoring and reassessment within 3 months for achievement of A1C target 1

Common Pitfalls to Avoid

• Therapeutic inertia - delaying intensification of therapy when targets aren't met 5
• Ignoring lifestyle factors alongside pharmacologic therapy 5
• Not monitoring for specific side effects of combination therapies, such as hypoglycemia with insulin/sulfonylurea combinations 5
• Failing to adjust therapy if targets are not achieved after 3 months 1

The TRIMASTER trial represents an important contribution to our understanding of how triple therapy compares to standard ADA-recommended care in the management of type 2 diabetes, particularly in addressing the multiple pathophysiological defects that characterize this progressive disease.