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

Abstract

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 2 . 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.

Impact of baseline characteristics on glycemic effects of add‐on saxagliptin or acarbose to metformin therapy: Subgroup analysis of the SMART study in Chinese patients with type 2 diabetes mellitus

“…A meta‐regression analysis of 78 randomized controlled trials with 20,053 patients showed that DPP‐4 inhibitors have greater efficacy in reducing HbA1c in patients with higher baseline values, with a 0.26% incremental reduction in the HbA1c response for every 1% increase of baseline HbA1c ( P < 0.001) 13 . Similar results were reported in the SUNSHINE and SPECIFY trials in Chinese patients with type 2 diabetes 9,12 . In the SUNSHINE trial, saxagliptin treatment was associated with larger reductions in HbA1c in patients with higher baseline values – the reductions in HbA1c ranged from –0.78% in patients with baseline HbA1c of <8.0% to –2.90% in those with baseline HbA1c ≥10.0% to ≤11% 9 .…”

“…The efficacy and safety of saxagliptin as monotherapy or combination therapy in Chinese patients with type 2 diabetes have been established in several studies 9‐12 . In the present study, saxagliptin as add‐on to metformin has shown consistent glycemic efficacy across a range of patient profiles.…”

“…In the SUNSHINE trial, saxagliptin treatment was associated with larger reductions in HbA1c in patients with higher baseline values – the reductions in HbA1c ranged from –0.78% in patients with baseline HbA1c of <8.0% to –2.90% in those with baseline HbA1c ≥10.0% to ≤11% 9 . In the 48‐week SPECIFY trial, the reductions in HbA1c with saxagliptin therapy ranged from –0.56% to –1.80% in patients with baseline HbA1c <8.0% and ≥9.0%, respectively 12 . In the present analysis, the reductions in HbA1c were numerically larger in patients with higher baseline HbA1c values, ranging from –0.77% in patients with HbA1c <8.0 to –1.16% in those with HbA1c ≥10.0%.…”

Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes: systematic review and pairwise and network meta-analysis of randomised controlled trials

“…We included 82 randomised controlled trials (fig 1) with 104 833 participants with type 2 diabetes in the traditional pairwise meta-analysis 343536373839404142434445464748495051525354555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107108109110111112113114115. Characteristics of studies and participants included in the pairwise meta-analysis are shown in table 1 and supplementary table C. The average age of participants was 59.4 years, and 39.7% (n=41 618) were female.…”

Harmful versus beneficial effects of using short-term combined oral antidiabetic therapy: ‎An open label comparative clinical trial ‎

“…Glimepiride is a long-acting sulfonylurea compound and, like other sulfonylureas, it can cause episodes of hypoglycemia and increase the body weight [1]. It has a beneficial effect on insulin resistance by producing better glycemic control [2]. Several studies highlight a non-harmful effect of glimepiride against cardiac diseases, but it carried also a higher risk of stroke [3].…”