Effects of saxagliptin added to sub-maximal doses of metformin compared with uptitration of metformin in type 2 diabetes: the PROMPT study

Abstract

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 A1c (HbA1c) (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) HbA1c: 7.71 (0.85; SAXA-MET); 7.80 (0.82; MET-UP). Adjusted mean reductions from baseline in HbA1c (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 (HbA1c < 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 HbA1c 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.