Hormone-substrate changes with exenatide plus dapagliflozin versus each drug alone: The randomized, active-controlled...

Area of Science:

• Endocrinology
• Metabolic Disorders
• Pharmacology

Background:

• Type 2 diabetes management often requires combination therapies to achieve glycemic control.
• Understanding the metabolic effects of individual and combined drug therapies is crucial for optimizing treatment strategies.

Purpose of the Study:

• To investigate the impact of once-weekly exenatide (EQW) plus dapagliflozin (Dapa) on plasma insulin, glucagon, and β-hydroxybutyrate (β-OH) in type 2 diabetes.
• To compare the effects of EQW + Dapa with individual therapies (EQW or Dapa) in patients inadequately controlled with metformin.

Main Methods:

• A randomized controlled trial (DURATION-8) involving 678 patients with type 2 diabetes.
• Patients were assigned to EQW + Dapa, EQW + placebo, or Dapa + placebo groups.
• Measurements included fasting and postprandial insulin and glucagon, fasting FFA, β-OH, and hematocrit.

Main Results:

• The EQW + Dapa combination led to intermediate changes in β-OH, FFA, and glycerol compared to individual agents.
• The insulin-to-glucagon ratio (I/Glg) response varied, with EQW + Dapa showing reduced increases compared to EQW alone.
• Patients with higher β-OH increases had lower fasting insulin and I/Glg, and were more often treated with Dapa + placebo.

Conclusions:

• The EQW + Dapa combination effectively managed metabolic parameters in type 2 diabetes patients.
• This combination therapy mitigated the rise in β-OH seen with Dapa and the increase in I/Glg with EQW.
• The combination may offer benefits by preserving therapeutic effects while reducing the risk of ketoacidosis.