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Effects of saxagliptin added to sub-maximal doses of metformin compared with uptitration of metformin in type 2 diabetes : the PROMPT study . OBJECTIVE The PROMPT study compared efficacy and tolerability of two treatment intensification strategies : adding saxagliptin or uptitrating metformin monotherapy , in patients with type 2 diabetes ( T2D ) and inadequate glycaemic control on a sub-maximal metformin dose . RESEARCH DESIGN AND METHODS In this double-blind , 24-week study , metformin-tolerant patients with T2D on metformin monotherapy were randomised to receive fixed-dose metformin 1500 mg/day , plus either add-on saxagliptin 5 mg/day ( SAXA-MET ) or a two-step metformin uptitration ( MET-UP ) to a maximum dose ( 2500 mg/day ) . CLINICAL TRIAL REGISTRATION NCT01006590 . MAIN OUTCOME MEASURES Primary : absolute change from baseline in glycated haemoglobin A ( 1c ) ( HbA ( 1c ) ) ( Week 24 ) . Secondary : proportion of patients achieving a therapeutic glycaemic response ( Week 24 ) ; change from baseline in fasting plasma glucose ( Week 24 ) ; safety and tolerability . Exploratory analyses comprised three patient-related questionnaires , including the validated 5-dimension Digestive Health Status Index ( DHSI ) . RESULTS A total of 286 patients were randomised : ( SAXA-MET : 147 ; MET-UP : 139 ) . Baseline mean ( SD ) HbA ( 1c ) : 7.71 ( 0.85 ; SAXA-MET ) ; 7.80 ( 0.82 ; MET-UP ) . Adjusted mean reductions from baseline in HbA ( 1c ) ( Week 24 ) : -0.47 % ( SAXA-MET ) ; -0.38 % ( MET-UP ) ; mean ( 95 % CI ) difference in treatment effect , -0.10 % ( -0.26 , 0.07 ) ; p = 0.260 . The proportion of patients ( 95 % CI ) achieving a therapeutic glycaemic response ( HbA ( 1c ) < 7 % ) : 43.8 % ( 34.8 , 49.6 ) ( SAXA-MET ) vs. 35.0 % ( 29.0 , 43.8 ) ( MET-UP ) . Of the five DHSI domains , mean ( 95 % CI ) differences were observed for diarrhoea-predominant score ( +0.8 [ -2.5 , 4.0 ] vs. +7.9 [ 4.6 , 11.2 ] ) and dysmotility score ( -0.5 [ -2.0 , 1.0 ] vs. +1.9 [ 0.3 , 3.4 ] ) , ( SAXA-MET and MET-UP , respectively ) . The most common adverse event was diarrhoea : 6.1 % ( SAXA-MET ) vs. 12.2 % ( MET-UP ) . CONCLUSIONS In metformin-tolerant patients with T2D ( inadequately controlled on sub-maximal metformin monotherapy ) , saxagliptin was well tolerated . Although HbA ( 1c ) reduction was not significantly different between treatment groups , the lower occurrence of gastrointestinal symptoms in the SAXA-MET group suggests that saxagliptin add-on treatment may be a suitable alternative treatment strategy to metformin uptitration .
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Intervention_Pharmacological
saxagliptin
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Intervention_Pharmacological
metformin
56681
Intervention_Pharmacological
metformin
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Intervention_Pharmacological
saxagliptin
56683
Intervention_Pharmacological
metformin monotherapy
56684
Intervention_Pharmacological
metformin
56685
Intervention_Pharmacological
fixed-dose metformin
56686
Intervention_Pharmacological
add-on saxagliptin 5 mg/day ( SAXA-MET )
56687
Intervention_Pharmacological
two-step metformin uptitration ( MET-UP )
56688
Outcome_Physical
glycated haemoglobin A ( 1c ) ( HbA ( 1c ) )
56689
Outcome_Physical
therapeutic glycaemic response
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Outcome_Physical
fasting plasma glucose ( Week 24 )
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Outcome_Other
safety and tolerability
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Outcome_Physical
Baseline mean ( SD ) HbA ( 1c )
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Outcome_Physical
baseline in HbA ( 1c )
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Outcome_Physical
therapeutic glycaemic response
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Outcome_Physical
diarrhoea-predominant