Safety effect of combination therapy with Liraglutide plus metformin on HGP and HBA1C vs each therapy alone in patients with DM T2

Abstract

Background;Main hormons involved in regulation of glucose are glucagon like peptid GLP-1 and glucose dependent insulotropic polipeptid GIP .Both of them are inactivated by the enzim dipeptil peptidasa -4 (DPP-4) .Incretin based therapies include GLP -1 receptor agonist and DPP-4 inhibitors wich main actions are to increase secretion of insulin and inhibit secretion of glucagon . Objectives ; providing review of clinical trials of liraglutide-SGLT2 inhibitors cause an increase in HGP accompanied with an increase in plasma glucagon concentration .Increase in plasma glucagon concentration is partly responsible for the increase in HGP. The aim of study was to examine whether inhibition of glucagon secretion by liraglutide can prevent the increase in HGP. Research and methods ;51 T2DM patients(age=55+-1 year;45% female;BMI=35,6+-0,9;diabetes duration =7,8+-0,9 year;FPG=175+-7;HbA1=8,5+-0,1%) were randomized to receive for 14 weeks(i)metformin 1g ;(ii)liraglutide1,8 mg;or(iii)metformin 1g plus liraglutide1,8 mg. HGP(measured with 3-3H-glucose infusion) and plasma glucagon concentration were measured before and after 14 weeks of treatment. Results ;Metformin monotherapy caused a significant reduction in HbA1c(-1,1-+0,2%,p<0,01) accompanied with an increase in plasma glucagon concentration (by 28%,p<0,05)which lasted for 14 weeks. Liraglutide monoterapy caused a 1,6+-0,5%(p<0,01)reduction in HbA1C accompanied by a small(6 %) reduction in HGP (P=ns)without significant change in fasting plasma glucagon concentration. The combination of metformin plus liraglutide caused a greater reduction in HBa1c(1,9-+0,5%,p<0,05vs metformin and p=NS vs liraglutide)and attenuated the increase in fasting plasma glucagon and basal HGP at 14 weeks . Conclusion ;These results;1)support a possible role for increased plasma glucagon levels in the long term maintenance of increase in HGP caused by SGLT2i,and 2.)suggest that factors other than in addition to glucagon contribute to the initiation of the increase in HGP