Comparative effect of saxagliptin and glimepiride with a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in patients uncontrolled with metformin therapy: Results from the SPECIFY study, a 48-week, multi-centre, randomized, controlled trial.

Aims: To compare the efficacy and safety of saxagliptin and glimepiride in type 2 diabetes (T2D) patients who are inadequately controlled with metformin monotherapy.

Materials And Methods: In this 48-week, multi-centre, open-label, randomized, parallel trial (NCT02280486, clinicaltrials.gov), a total of 388 T2D patients were randomized 1:1 to saxagliptin or glimepiride groups. The primary endpoint was achievement of HbA1c <7.0%, without hypoglycaemia, defined as blood glucose <3.9 mmol/L and weight gain <3.0% after 48 weeks of treatment.

Results: Over 48 weeks, a greater proportion of patients achieved the primary endpoint with saxagliptin compared with glimepiride (43.3% vs 31.3%; odds ratio, 1.38, 95% CI, 1.05-1.82; P = 0.019), especially among patients with baseline HbA1c <8.0%, duration <5 years or baseline BMI ≥25 kg/m . Mean reduction in HbA1c was similar in the two treatment groups at Week 48 (-0.94% with saxagliptin vs -0.98% with glimepiride; P = 0.439). Bodyweight decreased with saxagliptin, but increased with glimepiride over the treatment period, and the treatment difference was -1.6 kg (P < 0.001) at Week 48. The proportion of patients experiencing hypoglycaemia was much lower with saxagliptin vs glimepiride (3.1% vs 12.8%; P < 0.001).

Conclusions: This study provides evidence that, compared to glimepiride, saxagliptin more effectively achieves a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in T2D patients who are inadequately controlled with metformin monotherapy, especially in overweight patients with moderate hyperglycaemia and a relatively short duration of diabetes.