Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes: the TriMaster...

Area of Science:

• Endocrinology
• Pharmacogenomics
• Metabolic Diseases

Background:

• Precision medicine tailors treatments based on individual characteristics.
• Differential drug response in type 2 diabetes (T2D) is crucial for therapy selection but underexplored.
• Previous research has not directly examined differential drug responses based on BMI and eGFR in T2D.

Purpose of the Study:

• To test if individuals with BMI > 30 kg/m² show greater glucose lowering with thiazolidinediones versus DPP4 inhibitors.
• To test if individuals with eGFR 60-90 ml/min/1.73 m² show greater glucose lowering with DPP4 inhibitors versus SGLT2 inhibitors.
• To evaluate the utility of simple clinical measures for personalized T2D drug selection.

Main Methods:

• A randomized, double-blind, three-way crossover trial involving 525 people with T2D.
• Treatments included sitagliptin (DPP4 inhibitor), canagliflozin (SGLT2 inhibitor), and pioglitazone (thiazolidinedione), each for 16 weeks, added to metformin.
• Primary endpoint: achieved HbA1c difference between strata (BMI and eGFR) for the drug pairs.

Main Results:

• Overall HbA1c reduction was similar across pioglitazone, sitagliptin, and canagliflozin.
• Participants with BMI > 30 kg/m² had significantly lower HbA1c with pioglitazone compared to sitagliptin (2.88 mmol/mol difference).
• Participants with eGFR 60-90 ml/min/1.73 m² had significantly lower HbA1c with sitagliptin compared to canagliflozin (2.90 mmol/mol difference).

Conclusions:

• Findings support using BMI and eGFR to identify optimal drug classes for glycemic control in T2D.
• Personalized therapy selection based on these clinical parameters can enhance treatment efficacy.
• The study highlights the potential of precision medicine in managing T2D effectively.