Study to determine the durability of glycaemic control with early treatment with a vildagliptin–metformin combination regimen vs. standard‐of‐care metformin monotherapy—the <scp>VERIFY</scp> trial: a randomized double‐blind trial

Section: Discussionmentioning

confidence: 85%

Efficacy and safety of combination therapy with vildagliptin and metformin versus metformin uptitration in Chinese patients with type 2 diabetes inadequately controlled with metformin monotherapy: a randomized, open‐label, prospective study (VISION)

Pan

et al. 2016

“…The endpoints assessed included: (a) number of patients with HbA1c above 9% (75 mmol/mol) at Week 24 or who received rescue medication because of failure to achieve pre‐specified glycaemic targets or who discontinued treatment because of lack of glycaemic control, and (b) time to rescue medication usage or study discontinuation because of failure to achieve glycaemic targets up to 24 weeks of treatment. Durability of glycaemic control was assessed as CoF for ΔHbA1c, based on an earlier study . CoF was measured using the slope from a random coefficient model of ΔHbA1c over Weeks 18–24, excluding data following rescue medication usage.…”

Section: Methodsmentioning

confidence: 99%

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

Bailey

Prato

Wei

et al. 2019

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.

“…The VERIFY (Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes mellitus) trial is the first study to investigate the long‐term clinical benefits of early combination treatment with the DPP‐4 inhibitor vildagliptin and metformin vs standard of care (metformin monotherapy) with vildagliptin added in a stepwise manner. This ongoing 5‐year study should provide insights into whether early combination treatment may slow β‐cell deterioration and provide long‐term clinical benefits to patients, and indicate whether this approach is superior to a stepwise approach …”

Section: Combination Therapymentioning

confidence: 99%

Initiating therapy in patients newly diagnosed with type 2 diabetes: Combination therapy vs a stepwise approach

Cersósimo

Johnson

Chovanes³

et al. 2017

There is clear evidence that achieving glycaemic targets reduces the risk of developing complications as a result of type 2 diabetes (T2D). Many patients, however, continue to have suboptimal glycaemic control because of issues that include unclear advice on how to achieve these targets as well as clinical inertia. The two management approaches recommended for patients newly diagnosed with T2D are stepwise and combination therapy, each of which has advantages and disadvantages. Stepwise therapy may result in good patient adherence and allow greater individualization of therapy, and minimization of side effects and cost, and so may be appropriate for patients who are closer to goal. Stepwise therapy, however, may also lead to frequent delays in achieving glycaemic goals and longer exposure to hyperglycaemia. Combination therapy, which is now emerging as an important therapy option, has a number of potential advantages over stepwise therapy, including reduction in clinical inertia and earlier and more frequent achievement of glycated haemoglobin goals by targeting multiple pathogenic mechanisms simultaneously, which may more effectively delay disease progression. Compared with stepwise therapy, the disadvantages of combination therapy include reduced patient adherence resulting from complex, multi-drug regimens, difficulty determining the cause of poor efficacy and/or side effects, patient refusal to accept disease, and higher cost. Fixed-dose and fixed-ratio combinations are novel therapeutic approaches which may help address several issues of treatment complexity and patient burden associated with combination therapy comprising individual drugs. The choice of which drugs to administer and the decision to use stepwise vs combination therapy, however, should always be made on an individualized basis.