Diabetes Care recently published an article which evaluates the combinatorial treatment effect of canagliflozin plus liraglutide on HbA1c, endogenous glucose production (EGP), and body weight versus each therapy alone. Forty-five patients with poorly controlled HbA1c of 7-11% and with type 2 diabetes on metformin with or without sulfonylurea received a 9-h measurement of EGP with [3-3H]glucose infusion, after which they were randomized to receive liraglutide 1.2 mg/day (LIRA), canagliflozin 100mg/day (CANA), or liraglutide 1.2mg plus canagliflozin 100mg (CANA/LIRA) for 16 weeks. At 16 weeks, the EGP measurement was repeated.

      Study results showed that the mean decrease from baseline to 16 weeks in HbA1c was -1.67 ± 0.29% (P = 0.0001), -0.89 ± 0.24% (P = 0.002), and -1.44 ± 0.39% (P = 0.004) in patients receiving CANA/LIRA, CANA, and LIRA, respectively. The decrease in body weight was -6.0 ± 0.8 kg (P < 0.0001), -3.5 ± 0.5 kg (P < 0.0001), and -1.9 ± 0.8 kg (P = 0.03), respectively. CANA monotherapy caused a 9% increase in basal rate of EGP (P < 0.05), which was accompanied by a 50% increase (P < 0.05) in plasma glucagon-to-insulin ratio. LIRA monotherapy reduced plasma glucagon concentration and inhibited EGP. In CANA/LIRA-treated patients, EGP increased by 15% (P < 0.05), even though the plasma insulin response was maintained at baseline and the CANA-induced rise in plasma glucagon concentration was blocked.

      The work sheds light on the facts that all the three treatments caused significant weight loss. The decrease in body weight was -6.0 ± 0.8 kg (P < 0.0001), -3.5 ± 0.5 kg (P < 0.0001), and -1.9 ± 0.8 kg (P = 0.03) in participants receiving CANA/LIRA, CANA, and LIRA, respectively. The decrease in body weight caused by combination therapy with CANA/LIRA was additive and significantly greater than that caused by CANA alone (P = 0.01) and LIRA alone (P = 0.002). Further, the decrease in systolic blood pressure caused by CANA/LIRA was significantly greater (P = 0.03) than that cause by CANA and LIRA monotherapy. Similarly, all three therapies reduced diastolic blood pressure also. In summary, the combination of liraglutide plus c anagliflozin produced only a markedly less-than-additive decrease in HbA1c. Although combination therapy with agents from these two classes of antidiabetic drugs did not exert an additive action on glucose control as per the results, they could be very beneficial in obese patients with T2DM with respect to weight loss and blood pressure.