A Cross-control Study Of Insulin Combined With Dapagliflozin Or Acarbose In T1DM

Background:Type 1 diabetic patients are absolutely deficient in insulin due to the destruction of pancreatic β-cells and require lifelong insulin therapy.However,due to the destruction of pancreatic β-cells,the ability to regulate blood sugar is reduced.During insulin therapy,there are adverse events such as substandard blood sugar control,large blood sugar fluctuations,high risk of hypoglycemia,and weight gain.The long-term process will accelerate various complications of diabetes.Previous studies have shown that sodium-glucose transporter 2inhibitors and α-glucosidase inhibitors can help improve blood glucose in type 1 diabetes,but there has not been a controlled study report on the efficacy of insulin combined with these two drugs in type 1 diabetes.Objective:To observe the effects of insulin combined with sodium-glucose transporter 2inhibitor or α-glucosidase inhibitor on blood glucose,insulin dosage and safety in type 1diabetic patients,and compare the efficacy of these two treatment options.Methods: The trial was a crossover design,using dapagliflozin or acarbose as intervention methods.The trial lasted for 8 weeks.The included patients with type 1 diabetes wore a scanning glucose monitor for glucose monitoring during the trial period.During the first 1-2weeks,the insulin regimen was optimized and adjusted according to the blood glucose control situation.The blood glucose fluctuation control target was 3.9-10mmol/L,and the fasting blood glucose control target was 6.5-7.5mmol/L.The goal of blood glucose control was consistent throughout the trial.From the third week,they were randomly divided into 2 groups.From 3-4weeks,the first group was treated with dapagliflozin 10 mg qd,and the second group was treated with acarbose 50 mg tid.The 5-6 weeks is the wash-out period and from 7-8 weeks 2groups crossover;the first group is added with acarbose 50 mg tid and the second group is added with dapagliflozin 10 mg qd.Compare the effects of the first 1-2 weeks with the addition of dapagliflozin or acarbose with the baseline and compare the effects of the two regimens of dapagliflozin or acarbose.Results:1.Compared with baseline,the total daily insulin in the dapagliflozin group decreased by 6.51 U/d(38.45±12.13 U/d vs 31.94±10.54 U/d,P=0.009),and the average blood glucose standard deviation(SDBG)decreased by 0.79 mmol/L(3.67±1.32mmol/L vs 2.88±1.07mmol/L,P=0.003),the maximum blood glucose fluctuation range(LAGE)decreased by 2.17mmol/L(11.98±4.10mmol/L vs 9.81±3.30mmol/L,P=0.008),the average glucose decreased by1.36mmol/L(8.88±2.60mmol/L vs 7.52±1.75mmol/L,P=0.005),the average blood glucose fluctuation range(MAGE)decreased by 1.33mmol/L(8.65±3.14mmol)/L vs 7.32±2.57mmol/L,P=0.041),the postprandial blood glucose fluctuation range(PPGE)decreased by 0.91mmol/L(3.54±1.75mmol/L vs 2.63±1.08mmol/L,P=0.002),the target range Time within the target range(TIR)increased by 12.8%(55.4% vs 68.2%,P<0.001),time within the target range(TAR)decreased by 12.9%(33.4% vs 20.5%,P=0.007).Residual blood glucose evaluation index glycosylated hemoglobin(Hb A1c),fructosamine(FMN),time below target range(TBR),and body weight were not statistically significant.Compared with baseline,PPGE in the acarbose group significantly decreased by 1.0 mmol/L(3.54±1.75 mmol/L vs 2.54±0.93 mmol/L,P=0.001),and the Hb A1 c,TIR,TAR,TBR,SDBG,LAGE,MAGE,daily insulin dosage and body weight did not change significantly.3.Compared with the acarbose group,the daily insulin consumption in the dapagliflozin group decreased by 3.69 U/d(31.94±10.54 U/d vs 35.63±11.79 U/d,p=0.001),and Hb A1 c decreased by 0.24%(7.62±0.97)% vs7.86±1.22%,p=0.03),TIR increased by 12.2%(68.2% vs 56.0%,p=0.001),TAR decreased by 13.5%(20.5% vs 34.0%,p=0.001),SDBG decreased by0.65 mmol /L(2.88±1.07 mmol/L vs 3.53±1.05 mmol/L,p<0.001),LAGE decreased by1.93mmol/L(9.81±3.30 mmol/L vs 11.74±2.97 mmol/L,p<0.001),average glucose The value decreased by 1.46 mmol/L(7.52±1.75 mmol/L vs 8.98±1.97 mmol/L,p=0.005),and there was no significant difference in MAGE,PPGE,FMN,TBR,and body weight.4.Safety: The frequency of hypoglycemia compared with baseline in the dapagliflozin group or acarbose group was 1.32 times/day vs.1.50 times/day vs.1.46 times/day,which was not statistically significant(all P>0.05)There was no significant difference in the frequency of hypoglycemia between the dapagliflozin group and the acarbose group,and no serious adverse events occurred in each group.Conclusion:Insulin combined with dapagliflozin can improve the average value of TIR,TAR,SDBG,LAGE,MAGE,PPGE and glucose in T1 DM patients,and reduce the amount of insulin;insulin combined with acarbose can improve postprandial blood glucose levels in T1 DM patients.Compared with acarbose,dapagliflozin can reduce the daily insulin dosage of T1 DM patients and improve blood glucose fluctuations.Insulin combined with dapagliflozin or acarbose,respectively,does not increase the risk of hypoglycemia.No serious adverse events have occurred and it has good safety.