***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract Background The sodium-glucose co-transporter-2 ( SGLT-2 ) inhibitors have been reported to increase both low-density lipoprotein ( LDL ) and high-density lipoprotein (HDL)-cholesterol ( C ) . This study aim ed to determine how SGLT-2 inhibitors affect LDL and HDL-C subspecies . Methods This single center , open-label , r and omized , prospect i ve study included 80 patients with type 2 diabetes taking prescribed oral hypoglycemic agents . Patients were allocated to receive dapagliflozin ( n = 40 ) or sitagliptin ( n = 40 ) as add-on treatment . Fasting blood sample  s were collected before and 12 weeks after this intervention . Small dense ( sd ) LDL-C , large buoyant ( lb ) LDL-C , HDL2-C , and HDL3-C levels were determined using our established homogeneous assays . Statistical comparison of blood parameters before and after treatment was performed using the paired t test . Results Dapagliflozin and sitagliptin comparably decreased HbA1c ( 0.75 and 0.63 % , respectively ) . Dapagliflozin significantly decreased body weight , systolic blood pressure , plasma triglycerides and liver transaminases , and increased adiponectin ;  sitagliptin did not alter these measurements . LDL-C and apolipoprotein ( apo ) B were not significantly changed by dapagliflozin , whereas HDL-C and apo AI were increased . Dapagliflozin did not alter concentrations of LDL-C , but sd LDL-C decreased by 20 % and lb LDL-C increased by 18 % . Marked elevation in lb LDL-C ( 53 % ) was observed in individuals ( n = 20 ) whose LDL-C was elevated by dapagliflozin . However , sd LDL-C remained suppressed ( 20 % ) . Dapagliflozin increased HDL2-C by 18 % without affecting HDL3-C.  Sitagliptin did not alter plasma lipids or lipoprotein subspecies . Conclusions A SGLT-2 inhibitor , dapagliflozin suppresses potent atherogenic sd LDL-C and increased HDL2-C , a favorable cardiometabolic marker . Although LDL-C levels are elevated by treatment with dapagliflozin , this was due to increased concentrations of the less atherogenic lb LDL-C. However , these findings were not observed after treatment with dipeptidyl peptidase-4 inhibitor , sitagliptin . Trial registration UMIN Clinical Trials Registry ( UMIN000020984 OBJECTIVE To evaluate the efficacy and safety of combinations of empagliflozin/linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin . RESEARCH DESIGN AND METHODS Subjects were r and omized to a combination of empagliflozin 25 mg/linagliptin 5 mg ( n = 137 ) , empagliflozin 10 mg/linagliptin 5 mg ( n = 136 ) , empagliflozin 25 mg ( n = 141 ) , empagliflozin 10 mg ( n = 140 ) , or linagliptin 5 mg ( n = 132 ) as add-on to metformin for 52 weeks . The primary end point was change from baseline in HbA1c at week 24 . RESULTS At week 24 , reductions in HbA1c ( mean baseline 7.90–8.02 % [ 62.8–64.1 mmol/mol ] ) with empagliflozin/linagliptin were superior to those with empagliflozin or linagliptin alone as add-on to metformin ; adjusted mean ( SE ) changes from baseline were −1.19 % ( 0.06 ) ( −13.1 mmol/mol [ 0.7 ] ) with empagliflozin 25 mg/linagliptin 5 mg , −1.08 % ( 0.06 ) ( −11.8 mmol/mol [ 0.7 ] ) with empagliflozin 10 mg/linagliptin 5 mg , −0.62 % ( 0.06 ) ( −6.8 mmol/mol [ 0.7 ] ) with empagliflozin 25 mg , −0.66 % ( 0.06 ) ( −7.2 mmol/mol [ 0.7 ] ) with empagliflozin 10 mg , and −0.70 % ( 0.06 ) ( −7.6 mmol/mol [ 0.7 ] ) with linagliptin 5 mg ( P < 0.001 for all comparisons ) . In these groups , respectively , 61.8 , 57.8 , 32.6 , 28.0 , and 36.1 % of subjects with baseline HbA1c ≥7 % ( ≥53 mmol/mol ) had HbA1c < 7 % ( < 53 mmol/mol ) at week 24 . Efficacy was maintained at week 52 . The proportion of subjects with adverse events ( AEs ) over 52 weeks was similar across treatment arms ( 68.6–73.0 % ) , with no hypoglycemic AEs requiring assistance . CONCLUSIONS Combinations of empagliflozin/linagliptin as second-line therapy for 52 weeks significantly reduced HbA1c compared with the individual components and were well tolerated OBJECTIVE To evaluate the efficacy and safety of empagliflozin/linagliptin in subjects with type 2 diabetes . RESEARCH DESIGN AND METHODS Subjects not receiving antidiabetes therapy for ≥12 weeks were r and omized  to empagliflozin 25 mg/linagliptin 5 mg ( n = 137 ) , empagliflozin 10 mg/linagliptin 5 mg ( n = 136 ) , empagliflozin 25 mg ( n = 135 ) , empagliflozin 10 mg ( n = 134 ) , or linagliptin 5 mg ( n = 135 ) for 52 weeks . The primary end point was change from baseline in HbA1c at week 24 . RESULTS Mean HbA1c at baseline was 7.99–8.05 % ( 64 mmol/mol ) . At week 24 , adjusted mean ( SE ) changes from baseline in HbA1c with empagliflozin 25 mg/linagliptin 5 mg , empagliflozin 10 mg/linagliptin 5 mg , empagliflozin 25 mg , empagliflozin 10 mg , and linagliptin 5 mg were −1.08 (0.06)% ( −11.8 [ 0.7 ] mmol/mol ) , −1.24 (0.06)% ( −13.6 [ 0.7 ] mmol/mol ) , −0.95 (0.06)% ( −10.4 [ 0.7 ] mmol/mol ) , −0.83 (0.06)% ( −9.1 [ 0.7 ] mmol/mol ) , and −0.67 (0.06)% ( −7.3 [ 0.7 ] mmol/mol ) , respectively . Reductions in HbA1c were significantly greater for empagliflozin 25 mg/linagliptin 5 mg compared with linagliptin 5 mg ( P < 0.001 ) but not compared with empagliflozin 25 mg and were significantly greater for empagliflozin 10 mg/linagliptin 5 mg compared with the individual components ( P < 0.001 for both ) . At week 24 , 55.4 % , 62.3 % , 41.5 % , 38.8 % , and 32.3 % of subjects with baseline HbA1c ≥7 % ( ≥53 mmol/mol ) reached HbA1c < 7 % with empagliflozin 25 mg/linagliptin 5 mg , empagliflozin 10 mg/linagliptin 5 mg , empagliflozin 25 mg , empagliflozin 10 mg , and linagliptin 5 mg , respectively . Efficacy was maintained at week 52 . The proportion of subjects with adverse events ( AEs ) over 52 weeks was similar across groups ( 68.9–81.5 % ) , with no confirmed hypoglycemic AEs . CONCLUSIONS Reductions from baseline in HbA1c with empagliflozin/linagliptin were significantly different versus linagliptin and empagliflozin 10 mg but not versus empagliflozin 25 mg . Empagliflozin/linagliptin was well tolerated Chronic hyperglycemia impairs insulin action , result ing in glucotoxicity , which can be ameliorated in animal models by inducing glucosuria with renal glucose transport inhibitors . Here , we examined whether reduction of plasma glucose with a sodium-glucose cotransporter 2 ( SGLT2 ) inhibitor could improve insulin-mediated tissue glucose disposal in patients with type 2 diabetes . Eighteen diabetic men were r and omized to receive either dapagliflozin ( n = 12 ) or placebo ( n = 6 ) for 2 weeks . We measured insulin-mediated whole body glucose uptake and endogenous glucose production ( EGP ) at baseline and 2 weeks after treatment using the euglycemic hyperinsulinemic clamp technique . Dapagliflozin treatment induced glucosuria and markedly lowered fasting plasma glucose . Insulin-mediated tissue glucose disposal increased by approximately 18 % after 2 weeks of dapagliflozin treatment , while placebo-treated subjects had no change in insulin sensitivity . Surprisingly , following dapagliflozin treatment , EGP increased substantially and was accompanied by an increase in fasting plasma glucagon concentration . Together , our data indicate that reduction of plasma glucose with an agent that works specifically on the kidney to induce glucosuria improves muscle insulin sensitivity . However , glucosuria induction following SGLT2 inhibition is associated with a paradoxical increase in EGP . These results provide support for the glucotoxicity hypothesis , which suggests that chronic hyperglycemia impairs insulin action in individuals with type 2 diabetes OBJECTIVE This study compared the efficacy and safety of dual add-on of saxagliptin plus dapagliflozin versus saxagliptin and dapagliflozin added on alone in patients with type 2 diabetes poorly controlled with metformin . RESEARCH DESIGN AND METHODS This was a double-blind trial in adults with HbA1c ≥8.0 % and ≤12.0 % ( 64–108 mmol/mol ) , r and omized to saxagliptin ( SAXA ) ( 5 mg/day ) plus dapagliflozin ( DAPA ) ( 10 mg/day ; n = 179 ) , or SAXA ( 5 mg/day ) and placebo ( n = 176 ) , or DAPA ( 10 mg/day ) and placebo ( n = 179 ) on background metformin extended release ( MET ) ≥1,500 mg/day . Primary objective compared changes from baseline in HbA1c with SAXA+DAPA+MET versus SAXA+MET and DAPA+MET . RESULTS Patients had a mean baseline HbA1c of 8.9 % ( 74 mmol/mol ) , diabetes duration of 7.6 years , and a BMI of 32 kg/m2 . At week 24 , the adjusted mean change from the baseline HbA1c was –1.5 % ( –16.1 mmol/mol ) with SAXA+DAPA+MET versus –0.9 % ( –9.6 mmol/mol ) with SAXA+MET ( difference −0.59 % [ –6.4 mmol/mol ] , P < 0.0001 ) and –1.2 % ( –13.1 mmol/mol ) with DAPA+MET ( difference −0.27 % [ 3.0 mmol/mol ] , P < 0.02 ) . The proportion of patients achieving HbA1c < 7 % ( 53 mmol/mol ) was 41 % with SAXA+DAPA+MET versus 18 % with SAXA+MET and 22 % with DAPA+MET . Urinary and genital infections occurred in ≤1 % of patients receiving SAXA+DAPA+MET . Hypoglycemia was infrequent , with no episodes of major hypoglycemia . CONCLUSIONS In this first report of adding a well-tolerated combination of saxagliptin plus dapagliflozin to background metformin therapy in patients poorly controlled with metformin , greater improvements in glycemic control were obtained with triple therapy by the dual addition of saxagliptin and dapagliflozin than dual therapy with the addition of saxagliptin or dapagliflozin  alone CONTEXT Dipeptid 
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The risk of hypoglycemia increased in SGLT2i/DPP4i compared to that in PCB/DPP4i only when insulin or sulfonylureas were included as a background therapy .
The risk of urinary tract infection was not increased in SGLT2i/DPP4i ; however , the risk of genital infection increased upon adding SGLT2 inhibitors to pre-existing DPP4 inhibitors .
In conclusion , compared to PCB/DPP4i , SGLT2i/DPP4i  achieved better glycemic control and greater weight reduction without increasing the risk of hypoglycemia and urinary tract infection in patients with inadequately controlled T2DM