Durability of glycaemic control with dapagliflozin, an SGLT2 inhibitor, compared with saxagliptin, a DPP4 inhibitor, in patients with inadequately controlled type 2 diabetes

Abstract

Dapagliflozin is associated with greater reductions in HbA1c and weight than saxagliptin in management of type 2 diabetes mellitus (T2DM). The present post hoc analyses compared the durability of these effects over short‐ and long‐term follow‐up in patients with T2DM who were inadequately controlled with metformin (≥1500 mg/day) and who were receiving either dapagliflozin (10 mg/day) or saxagliptin (5 mg/day). Failure of glycaemiccontrol was assessed using the slope of the change in HbA1c from baseline‐over‐time regression line (coefficient of failure [CoF]). CoF was compared directly (dapagliflozin vs saxagliptin) over the short term (NCT01606007, 24 weeks) and indirectly (placebo‐adjusted) over the long term (NCT00528879 and NCT00121667, 102 weeks). A low CoF value indicated greater durability. CoF was lower for dapagliflozin versus saxagliptin over 18–24 weeks (−1.38%/year; 95% CI, −2.41 to −0.35; P = .009) and 20–102 weeks (−0.37%/year; 95% CI, −0.73 to −0.02; P = .04). Fewer dapagliflozin‐treated patients versus saxagliptin‐treated patients required rescue medication or discontinued the study because of failure to achieve glycaemic control at 24 weeks (3.4% vs 9.4%; P = .0191). In patients with T2DM who were inadequately controlled with metformin, dapagliflozin was associated with greater durability of glycaemic control than saxagliptin over 18–24 and 20–102 weeks.

Real-World Evidence for Long-Term Safety and Effectiveness of Ipragliflozin in Japanese Patients with Type 2 Diabetes Mellitus: final Results of a 3-Year Post-Marketing Surveillance Study (STELLA-LONG TERM)

“…A previous summary of clinical trials pointed out that SGLT2 inhibitors appear to show a relatively longer duration of effect on glycemic control (in terms of time to return of HbA1c to baseline at a maximum dose of single oral agent) than other oral antidiabetic drugs, including metformin, SU and DPP-4 inhibitors [45]. Similarly, a recent post hoc analysis suggested a greater durability of glycemic control with the SGLT2 inhibitor dapagliflozin, in patients with T2DM who were inadequately controlled with metformin, compared to that with the DPP-4 inhibitor saxagliptin [46].…”

Durability of glycaemic control in type 2 diabetes: A systematic review and meta‐analysis for its association with body weight changes

“…CoF can be used as a surrogate marker to quantify the decline in beta‐cell function. We observed lower CoF in the treatment groups of patients who did not experience weight gain 7,8,10,18,29 . Losing weight has been reported to benefit beta‐cell function 11,46,47 through a mechanism that is not completely understood 48–51 .…”

“…received insulin therapy. Furthermore, eight studies reported outcomes for the treatment failure rate, [7][8][9] the rescue medication rate, [17][18][19][20] or the treatment intensification rate 10 (Table S3). We also analysed seven randomized controlled trials reporting the long-term effect of weight management on glycaemic durability to compare the long-term therapeutic efficacy of different degrees of weight loss.…”

“…The CoF is a simple tool developed by Wallace and Mathews to qualify diabetes progression in terms of beta-cell deterioration, 15 which was defined as the slope of the least-squares regression line of the glycaemic index versus time and used to assess therapeutic durability in many studies. 7,9,18,29 The CoF allows assessment of beta-cell failure based on a certain index of glycaemia 15 and has an inverse association with changes in homeostatic model assessment (HOMA)2-beta. In our analysis, the pooled CoF from 50 articles was 0.123 ± 0.022%/year (P < .001).…”

Efficacy and safety of dapagliflozin plus saxagliptin vs monotherapy as added to metformin in patients with type 2 diabetes

“…Recently study found that the durability of glycemia control with dapagliflozin was greater than saxagliptin in patients with T2DM, which lasted more than 24 weeks. [ 29 ] Other study indicated that dapagliflozin plus saxagliptin as add-on to metformin also exhibit better tolerance in glycemia control. [ 30 ]…”