received wisdom indicated that acarbose could improve mean haemoglobin a1c ( hba1c ) levels in patients with type 2 diabetes mellitus ( t2 dm ) by reducing plasma glucose concentration [ 1 , 2 ] . furthermore , acarbose could decrease total daily insulin dose and increase the response to insulin in patients with t2 dm [ 3 , 4 ] . several studies have shown that postprandial glucose ( ppg ) is an independent risk factor for cardiovascular disease . reported that acute glucose fluctuations during postprandial periods played a crucial role in oxidative stress . by reducing postprandial excursions , studies have demonstrated that acarbose was effective in reducing postprandial glycemic excursions ; combined administration of acarbose with alogliptin therapy resulted in decreasing plasma glucose fluctuations . addition of acarbose to patients with t2 dm who are inadequately controlled with insulin or patients initiated with insulin significantly lowers hba1c and postprandial glucose levels [ 10 , 11 ] . recent studies have indicated that even when hba1c is similar , glucose excursions may differ significantly . we therefore performed an opened and unblended study using a continuous glucose monitoring system ( cgms ) to assess the efficacy of adding acarbose to insulin therapy on plasma glucose control in patients with t2 dm . one hundred and thirty - four consecutive newly diagnosed patients with t2 dm were admitted to hospital and received therapy with continuous subcutaneous insulin infusion ( csii ) for initial rapid correction of hyperglycaemia . after 46-day premixed insulin titration period , patients were then randomized into two groups [ acarbose plus insulin isophane protamine recombinant human insulin 30/70 ( premixed 30/70 , twice daily ) group and premixed insulin 30/70 twice - daily alone group ] . the patients aged 1875 years with a body mass index ( bmi ) calculated as weight in kilograms divided by the square of height in meters , 1840  kg / m , and hba1c range 9.012.0% . patients were excluded if they had acute or severe chronic diabetic complications , serious systemic disease , or poor medication compliance . patients with known cancers , known allergies to insulin or acarbose , and an assessment by the researchers as not suitable to participate were excluded [ 13 , 14 ] . the study was approved by the ethics committee of nanjing first hospital . written informed consent was obtained from the patients prior to the study . after 7-day csii therapy , all patients achieved stable glycemic control ( the fasting capillary blood glucose was less than 6.1  mmol / l and capillary blood glucose at 2  h after each of three meals was less than 8.0 initial premixed 30/70 doses were calculated as 0.40.5  iu / kg , and doses were subsequently adapted according to plasma glucose values obtained by self - monitoring . investigators titrated insulin doses on an individual - patient basis at the titration algorithm ( if the fasting blood glucose level was less than 4.4 mmol / l , the insulin dose was reduced 2 units ; if the fasting blood glucose level was within 4.4 to 6.1  mmol / l , the insulin dose was unchanged ; if the fasting blood glucose level was within 6.2 to 7.8 , 7.9 to 10.0 , and > 10.0 mmol / l , the insulin dose was increased subsequently by 2 , 4 , and 6 units , resp . ) . premixed insulin doses remained unchanged and recorded , if euglycemic control was achieved for two consecutive days . glucobay , bayer , germany ) plus premixed insulin 30/70 ( twice daily ) or premixed insulin 30/70 twice daily alone . continuous glucose monitoring ( cgm ) data were obtained with medtronic minimed cgms gold ( medtronic incorporated , northridge , usa ) for at least 3 days on completion of 2 weeks randomised treatment . all patients were subjected to 3 consecutive days cgms in hospital by the specialist nurse . shortly , the cgms sensor was subcutaneously embedded at day 0 around 16:00 - 17:00 . the patients continued with the sensor for 3 consecutive days , if cgms was going well . the study nurse inputted at least 4 calibration readings per day . at day 3 , around 16:00 - 17:00 , subjects had the sensor removed and the cgms data were saved by the investigator . the 24  h mean amplitude of glycemic excursions ( mage ) and other plasma glucose fluctuation parameters such as the 24  h mean blood glucose ( mbg ) , the percentage time duration ( % ) , and the incremental area under curve ( auc ) of plasma glucose > 10.0  mmol / l and < 3.9  mmol / l were calculated , and hypoglycemia episodes were also recorded . mage was calculated for each patient by measuring the arithmetic mean of the ascending and descending excursions between consecutive peaks and nadirs for the same 24  h period ; only absolute excursion values > 1 sd were considered . secondary endpoints were the 24  h mbg , the auc for hypoglycaemia ( defined as sensor glucose values < 3.9  mmol / l ) , and hyperglycaemia ( sensor glucose values > 10 mmol / l ) ; the times spent in hypoglycaemia and hyperglycaemia were also analyzed . statistical analysis was performed using spss software ( version 17.0 ; spss , inc . , shapiro - wilk test was used to assess the distribution of data . normally distributed and continuous variables are presented as mean ( standard deviation , sd ) . nonnormally distributed variables were presented as median ( iqr ) and logarithmically transformed before analysis . patients reached glycaemic goals in 4.3  2.6 and 1.5  1.4 days during the csii period and the premixed insulin titration period , respectively . table 1 showed the baseline data on the 134 patients with t2 dm who were randomized to the two treatment groups . the mage measured by cgms in the group of diabetes patients treated with insulin alone ( 7.50  3.28  mmol / l ) was significantly higher than the group with added acarbose ( 5.56  2.16  mmol / l , p = 0.044 , figure 1 ) . figure 2 shows that when acarbose was added , the incremental auc > 10  mmol / l ( significant hyperglycemia ) detected by cgms was significantly decreased ( 0.5 [ 0.03,0.9 ]  mmol / l per day , p = 0.037 ) compared to the group treated with insulin alone ( 0.85 [ 0.23,1.4 ]  mmol / l per day ) . table 2 compared the 24  h mean glucose levels and the percentage of time of significant hyperglycemia ( glucose > 10  mmol / l ) and significant hypoglycemia ( glucose < 3.9  mmol / l ) between the two groups . there were no statistically significant differences between the acarbose group and insulin monotherapy group in the 24  h mbg , the standard deviation ( sd ) of the 24  h mbg , the percentage time duration of hyperglycemia ( glucose > 10  mmol / l ) , hypoglycemia ( glucose < 3.9  mmol / l ) , the number of hyperglycemia ( glucose > 10  mmol / l ) episodes , and the number of hypoglycemia excursion ( glucose < 3.9  mmol / l ) episodes ( see table 2 ) . we also compared the risk of severe hypoglycemia ( glucose < 2.8  mmol / l ) between the two groups .   figure 3 showed that the acarbose group had significantly less severe hypoglycemia ( 0.41  0.20 versus 0.47  0.21  mmol / l per day , p = 0.042 ) . adverse events were reported by 9 acarbose+ patients and 3 acarbose patients , consisting of digestive disorders . in the current study , we observed that the addition of acarbose to insulin improves glucose fluctuation in patients with t2 dm , as measured by mage , and reduced the risk of severe hypoglycemia . previous studies have shown that administration of acarbose in patients with t2 dm with newly initiated insulin or established insulin therapy improved hba1c levels . in a 20-week study , hba1c levels in patients with a combination of acarbose and insulin had an additional improvement of 0.5% compared with a placebo group . chiasson et al . reported a mean decrease in hba1c of 0.4% in patients already on insulin after 12-month addition of acarbose to the insulin therapy . an additional improvement has also been previously described in patients treated with acarbose over a 3-year period . hba1c is very useful as evidence of long - term improvement in mean glucose in the large scale clinical studies for t2 dm treatment [ 19 , 20 ] . patients with large glucose fluctuations around a similar mean may have implications on the risk for long - term diabetic complications [ 12 , 21 ] . in the present pilot study , we expected to see a reduction of postprandial plasma glucose values in acarbose plus insulin compared with insulin monotherapy patients owing to acarbose delaying in carbohydrate absorption . our data showed a remarkable improved mage with the addition of acarbose to insulin therapy compared with insulin monotherapy . this showed the inhibition of postprandial plasma glucose increases and reduction of excessive plasma glucose fluctuations when acarbose was administered . our findings are consistent with those of previous studies in the fact that acarbose regimens have a further postprandial plasma glucose lowering effect when supplementing insulin therapy [ 22 , 23 ] . in addition , we observed a significant reduction in severe hypoglycemia . it is now believed that postprandial hyperglycemia and acute glucose fluctuations may be important as independent risk factors for cardiovascular disease in patients with onset t2 dm , the overproduction of superoxide by the mitochondrial electron - transport chain , which induces a subsequent nitrosative stress , especially glucose fluctuations during postprandial periods . treatment of impaired glucose tolerant patients with long - term acarbose showed a 49% reduction in the risk of cardiovascular disease . studies also showed that acarbose improves postprandial endothelial function by improvement of postprandial hyperglycemia [ 27 , 28 ] . further studies will be needed to explore the add - on effect of acarbose for preventing complications in t2 dm . in the pilot study , newly diagnosed t2 dm patients ( with hba1c > 9.0% or fasting blood glucose higher than 11.1 mmol / l ) were treated with csii therapy for 7 days for initial rapid correction of hyperglycaemia . more attention should be paid to consider the use of a csii therapy in newly diagnosed t2 dm patients . use of csii therapy is regarded as a safe and valuable alternative in patients with newly diagnosed t2 dm . 2 - 3-week early csii in patients with newly diagnosed t2 dm in chinese population achieved prolonged glycaemic remission , as well as recovery and maintenance of -cell function compared with treatment with oral hypoglycaemic agents ; this early insulin replacement could achieve optimum glycaemic control for 1 year . in addition , the early restoration of -cell function and amelioration of insulin resistance might alter the natural history of t2 dm [ 14 , 29 ] . in conclusion , our data suggested that adjunct acarbose administration in the short term to patients on insulin monotherapy improves glucose fluctuation in patients with t2 dm .
background and aims . to evaluate the effect of adding acarbose on glycemic excursions measured by continuous glucose monitoring system ( cgms ) in patients with type 2 diabetes mellitus ( t2 dm ) already on insulin therapy . 
 materials and methods . 
 this was an opened and unblended study . 
 134 patients with t2 dm were recruited . 
 after initial rapidly corrected hyperglycaemia by continuous subcutaneous insulin infusion ( csii ) for 7 d , a 46-day premixed insulin titration period subsequently followed . 
 patients were then randomized 1  :  1 to acarbose plus insulin group or insulin therapy group for 2 weeks . cgms was used to measure glucose fluctuations for at least 3 days after therapy cessation . 
 results . 
 patients in acarbose plus insulin group achieved a significant improvement of mage compared to that of insulin therapy only group ( 5.56  2.16 versus 7.50  3.28  mmol / l , p = 0.044 ) , accompanied by a significant decrease in the incremental auc of plasma glucose concentration above 10.0  mmol / l ( 0.5 [ 0.03 , 0.9 ] versus 0.85 [ 0.23,1.4 ]  mmol / l per day , p = 0.037 ) . conclusions . 
 add - on acarbose to insulin therapy further improves glucose fluctuation in patients with t2 dm . 
 this study was registered with clinicaltrials.gov registration number chictr - trc-11001218 .