Initial combination therapy with DPP-IV inhibitors more effectively reduced MAGE than stepwise add-on therapies ( p = 0.006 ) , although no differences in MAGE were found based on HbA1c values .
These findings indicate that DPP-IV inhibitors are promising alternatives for reducing GV in type 2 diabetes patients .
Glycemic variability ( GV ) has been an emerging target for preventing complications related to type 2 diabetes .
For reducing GV , DPP-IV inhibitors have shown effectiveness compared to other oral anti-hyperglycemic drugs ( OADs ) , but systematic evaluation has yet to be existed .
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
BACKGROUND In patients with type 2 diabetes , intensive blood-glucose control with insulin or sulphonylurea therapy decreases progression of microvascular disease and may also reduce the risk of heart attacks . This study investigated whether intensive glucose control with metformin has any specific advantage or disadvantage . METHODS Of 4075 patients recruited to UKPDS in 15 centres , 1704 overweight ( > 120 % ideal bodyweight ) patients with newly diagnosed type 2 diabetes , mean age 53 years , had raised fasting plasma glucose ( FPG ; 6.1 - 15.0 mmol/L ) without hyperglycaemic symptoms after 3 months ' initial diet . 753 were included in a r and omised controlled trial , median duration 10.7 years , of conventional policy , primarily with diet alone ( n=411 ) versus intensive blood-glucose control policy with metformin , aim ing for FPG below 6 mmol/L ( n=342 ) . A secondary analysis compared the 342 patients allocated metformin with 951 overweight patients allocated  intensive blood-glucose control with chlorpropamide ( n=265 ) , glibenclamide ( n=277 ) , or insulin ( n=409 ) . The primary outcome measures were aggregates of any diabetes-related clinical endpoint , diabetes-related death , and all-cause mortality . In a supplementary r and omised controlled trial , 537 non-overweight and overweight patients , mean age 59 years , who were already on maximum sulphonylurea therapy but had raised FPG ( 6.1 - 15.0 mmol/L ) were allocated continuing sulphonylurea therapy alone ( n=269 ) or addition of metformin ( n=268 ) . FINDINGS Median glycated haemoglobin ( HbA1c ) was 7.4 % in the metformin group compared with 8.0 % in the conventional group . Patients allocated metformin , compared with the conventional group , had risk reductions of 32 % ( 95 % CI 13 - 47 , p=0.002 ) for any diabetes-related endpoint , 42 % for diabetes-related death ( 9 - 63 , p=0.017 ) , and 36 % for all-cause mortality ( 9 - 55 , p=0.011 ) . Among patients allocated intensive blood-glucose control , metformin showed a greater effect than chlorpropamide , glibenclamide , or insulin for any diabetes-related endpoint ( p=0.0034 ) , all-cause mortality ( p=0.021 ) , and stroke ( p=0.032 ) . Early addition of metformin in sulphonylurea-treated patients was associated with an increased risk of diabetes-related death ( 96 % increased risk [ 95 % CI 2 - 275 ] , p=0.039 ) compared with continued sulphonylurea alone . A combined analysis of the main and supplementary studies showed fewer metformin-allocated patients having diabetes-related endpoints ( risk reduction 19 % [ 2 - 33 ] , p=0.033 ) . Epidemiological assessment of the possible association of death from diabetes-related causes with the concurrent therapy of diabetes in 4416 patients did not show an increased risk in diabetes-related death in patients treated with a combination of sulphonylurea and metformin  ( risk reduction 5 % [ -33 to 32 ] , p=0.78 ) . INTERPRETATION Since intensive glucose control with metformin appears to decrease the risk of diabetes-related endpoints in overweight diabetic patients , and is associated with less weight gain and fewer hypoglycaemic attacks than are insulin and sulphonylureas , it may be the first-line pharmacological therapy of choice in these patients
Initial combination therapy with DPP-IV inhibitors more effectively reduced MAGE than stepwise add-on therapies ( p = 0.006 ) , although no differences in MAGE were found based on HbA1c values .
These findings indicate that DPP-IV inhibitors are promising alternatives for reducing GV in type 2 diabetes patients .
Glycemic variability ( GV ) has been an emerging target for preventing complications related to type 2 diabetes .
For reducing GV , DPP-IV inhibitors have shown effectiveness compared to other oral anti-hyperglycemic drugs ( OADs ) , but systematic evaluation has yet to be existed .