Alpha-glucosidase inhibitor is suitableas combination therapy of SGLT2 inhibitor

 in Japanese patients with type 2 diabetes:

Yoshihiko Suzuki MD.

According to open-label study of dapagliflozin (1), three drugs reduced HbA1c than

other oral hypoglycemic agents or GLP1 injection therapies.One is alpha-glucosedase inhibitor (aGI),the other is glinide, and the third is pioglitazone.

The reason why alpha-GI(aGI) is so effective has not been clarified.

 SGLT2i is characterized as having effect of lowing and stabilizing fasting blood glucose.However, patients are likely to have compensatory over-eating (COE) (2).

 Therefore, we speculate that postprandial hyperglycemia in the morning is emphasized.

According to the phase III study of luseogliflozin (3) even though blood glucose curve of SGLT2i after eating meal is lower than that of placebo curve, hyperinsulinemia remains.Therefore, when miglitol is added, we hypothesize that the hyperinsulinemic state will be alleviated to normal state, thereby leading to normal insulin secretion curve and helping to reduce insulin resistance.

 In addition, aGI, especially, miglitol, has more beneficial effect practically. It has a potential effect to induce mild diarrhea for some persons. SGLT2i, especially the product which has high selectivity to SGLT2 but not SGLT1, has potential effect to have constipation. Therefore, miglitol theoretically alleviates the tendency of constipation of high selective SGLT2i.

  Furthermore at our clinic, the complaints of gas, which is the side effect of aGI, seems to be reduced. We hypothesized that, because patients who received SGLT2i therapy are likely to go toilet frequently due to polyuria, they can fart in the toilet at the same time.

This time synergistic effect can let the patients not to suffer from the social trouble of fart, thereby making this adverse effect to be felt not so severe troublesome.

 Thus, after SGLT2i treatment, miglitol has gained more attractive effect, by having the synergistic effect to suppress the postprandial hyperglycemia in the morning and by alleviating the constipation, with less worry about the trouble of fart.

References

1.    Kaku K, et al. Dapagliflozin as monotherapy or combination therapy in Japanese patients with type 2 diabetes: an open-label study. Diabetes Ther. 5:415-33, 2014

2.  Suzuki Y.  Compensatory overeating (COE) could be a problem of diabetes diet education after sodium-glucose co-transporter 2 inhibitor treatment. The 6th international conf. on fixed combination of hypertension, dyslipidemia and diabetes, p18, 2015

3.    Seino Y et al. Efficacy and safety of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, phase 3 study. Curr Med Res Opin. 30:1245-55. 2014