Effect Of Saxagliptin And Metformin Monotherapy On Bone Metabolism And Body Fat Distribution In Patients With Newly Diagnosed Type 2 Diabetes

ObjectiveThe purpose of this study was to investigate the effects of saxagliptin and metformin monotherapy on bone metabolism and body fat distribution in patients with newly diagnosed type 2 diabetes mellitus（T2DM）,and to explore the relationship between bone metabolism and glycometabolism and lipid metabolism.Method:Through a randomized,parallel,open clinical trial,60 newly diagnosed and drug-native patients with T2DM were randomized to Saxagliptin（Sax,n=30）and Metformin（Met,n=30）group for a 24-week treatment,who were present in our hospital from October 2016 to June 2017.At the baseline and 24 weeks after treatment,the general information,glycometabolism and lipid metabolism index,Inflammation index,bone metabolism index（25（OH）D₃、β-CTx、OC、tPINP）,BMD（L1-L4、FN）and Body Fat Distribution（Fat%、VAT.Area、A/G、FMI）were arranged to measured.Results:1.Fifty-three patients completed the trial,including 27 in the Met group and 26 in the Sax group.Baseline parameters were comparable in both groups.2.General information:After 24 weeks of intervention,the BMI,body weight,and waist circumference were significantly decreased in the Met and Sax groups（all P<0.05）,between groups,body weight and waist circumference in the Met group decreased significantly compared with the Sax group（all P<0.05）,there was no statistical difference in BMI between the two groups（P>0.05）.3.Glycometabolism、lipid metabolism and Inflammation indicators:After 24weeks of intervention,FPG、HbA_1c、HOMA-IR、TC、TG、LDL-C and hs-CRP in Met and Sax patients decreased significantly（all P<0.05）,and HOMA-βincreased significantly（P>0.05）,between grougs,TC and LDL-C in the Met group were significantly lower than those in the Sax group（all P<0.05）,there was no significant difference in FPG、HbA_1c、HOMA-IR、HOMA-β、TG and hs-CRP between the two groups（all P>0.05）.4.Bone Metabolism:（1）After 24 weeks intervention,both OC and 25（OH）D₃in Met and Sax patients increased significantly（all P<0.05）,no significant changes in tP1NP andβ-CTx（all P>0.05）.there was no significant difference in tP1NP、OC、β-CTx and 25（OH）D₃ between the two groups（all P>0.05）;（2）Sax group after 24weeks intervention,the BMD of the femoral neck on the left side was significantly increased（P<0.05）,and the BMD of the lumbar spine was not significantly changed（P>0.05）.There was no significant change in the BMD of the lumbar spine and left femoral neck in the Met group（P>0.05）;Between groups,there was no statistical difference in BMD between lumbar spine and left femoral neck after intervention.（all P>0.05）5.Body fat distribution:After 24 weeks of intervention,VAT.Area、Fat%,A/G、FMI were significantly decreased in the Met and Sax groups（all P<0.05）;among them,the Met group had a good degree of decline in FMI.In the Sax group（P<0.05）,there was no significant difference in VAT.Area、Fat%and A/G between the two groups（all P>0.05）.6.Correlation Analysis of Bone Metabolism Indexes and glycometabolism,Lipid Metabolism Indexes:Spearman correlation analysis results showed that tPINP was negatively correlated with HbA_1cc and FPG（r=-0.280,-0.268,all P<0.05）,and there had no significant correlation with HOMA-IR,HOMA-β,TC,TG,and LDL-C（P>0.05）;β-CTx was negatively correlated with HbA1c and FPG（r=-0.303,-0.281,all P<0.05）,and had no significant correlation with HOMA-IR,HOMA-β,TC,TG,and LDL-C（all P>0.05）;OC,25（OH）D₃ and the glycometabolism,lipid metabolism indicators were not significantly related（all P>0.05）.7.In terms of safety,a total of 10 patients in the Met group developed gastrointestinal adverse reactions（37.04%）,including abdominal distension、diarrhea and abdominal pain.Appearance symptoms all resolved or disappeared in the first week or so.There was no gastrointestinal adverse reaction in the Sax group.No severe hypoglycaemic events occurred in either group of patients during the course of treatment.Conclusions:1.Metformin and saxagliptin can significantly improve the newly diagnosed T2DM patients with glucose,lipid metabolism,islet cell function and inflammation,increased OC,25（OH）D₃ levels,and promote bone formation;2.Saxagliptin can increase femoral neck BMD in patients with the newly diagnosed T2DM patients,and has no significant effect on lumbar spine BMD,while metformin has no significant effect on both.3.Metformin and saxagliptin can reduce the Fat%,VAT,Area,A/G and FMI,and improve body fat distribution in patients with the newly diagnosed T2DM patients,metformin has better effects on visceral fat area and fat mass index.