Ali Muhammed Ali 1, Robert Martinez 1, Hussein Al-Jobori 1, John Adams 1, Curtis Triplitt 1, Ralph DeFronzo 2, Eugenio Cersosimo 1, Muhammad Abdul-Ghani 1
Main idea: These results demonstrate that liraglutide failed to block the increase in EGP caused by canagliflozin despite blocking the rise in plasma glucagon and preventing the decrease in plasma insulin concentration caused by canagliflozin. The failure of liraglutide to prevent the increase in EGP caused by canagliflozin explains the lack of additive effect of these two agents on HbA1c.
Objective: To examine the effect of combination therapy with canagliflozin plus liraglutide on HbA1c, endogenous glucose production (EGP), and body weight versus each therapy alone.
Research design and methods: Forty-five patients with poorly controlled (HbA1c 7-11%) type 2 diabetes mellitus (T2DM) on metformin with or without sulfonylurea received a 9-h measurement of EGP with [3-3H] glucose infusion. At 16 weeks, the EGP measurement was repeated.
Results: The mean decrease from baseline to 16 weeks in HbA1c was -1.67±0.29% in patients receiving CANA/LIRA, CANA, and LIRA. CANA monotherapy caused a 9% increase in basal rate of EGP. LIRA monotherapy reduced plasma glucagon concentration and inhibited EGP in CANA-treated patients. EGP increased by 15% even though the plasma insulin response was maintained at baseline and the CANa-induced rise in plasma glucose concentration was blocked.