Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea

Abstract

AimThe broadly used combination of metformin and sulphonylurea (SU) often fails to bring patients to glycaemic goal. This study assessed the efficacy and safety of vildagliptin as add-on therapy to metformin plus glimepiride combination in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control.MethodsA multicentre, double-blind, placebo-controlled study randomized patients to receive treatment with vildagliptin 50 mg bid (n = 158) or placebo (n = 160) for 24 weeks.ResultsAfter 24 weeks, the adjusted mean change in haemoglobin A1c (HbA1c) was −1.01% with vildagliptin (baseline 8.75%) and −0.25% with placebo (baseline 8.80%), with a between-treatment difference of −0.76% (p < 0.001). Significantly more patients on vildagliptin achieved the HbA1c target <7% (28.3% vs. 5.6%; p < 0.001). The difference in fasting plasma glucose reduction between vildagliptin and placebo was −1.13 mmol/l (p < 0.001). In subgroup of patients with baseline HbA1c ≤8%, vildagliptin reduced HbA1c by 0.74% from baseline 7.82% (between-treatment difference: –0.97%; p < 0.001) with significantly more patients achieving the HbA1c target <7% (38.6% vs. 13.9%; p = 0.014). Vildagliptin was well tolerated with low incidence of hypoglycaemia, slightly higher than with placebo (5.1% vs. 1.9%) and no clinically relevant weight gain.ConclusionsVildagliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin plus glimepiride combination. The addition of vildagliptin was well tolerated with low risk of hypoglycaemia and weight gain. This makes vildagliptin an attractive treatment option for patients failing on metformin plus SU particularly in patients with baseline HbA1c ≤8%.

Dual Add-on Therapy in Type 2 Diabetes Poorly Controlled With Metformin Monotherapy: A Randomized Double-Blind Trial of Saxagliptin Plus Dapagliflozin Addition Versus Single Addition of Saxagliptin or Dapagliflozin to Metformin

“…These characteristics suggest relatively advanced disease with significant b-cell loss or dysfunction in these patients and are representative of poorly controlled patients. Several recent studies examining the safety and efficacy of triple oral therapy enrolled patients with mean baseline HbA 1c in the range of 7.8-8.8% (62-73 mmol/mol) with mean disease durations of 5-10 years (20,(35)(36)(37)(38)(39)(40)(41). Most of these studies examined a single-agent add-on to dual therapy and obtained placebo-corrected reductions in HbA 1c ranging from -0.4% to -0.9% (-4.4 to 9.8 mmol/mol).…”

Management of type 2 diabetes mellitus: insights into prescribing trends

“…2 The proclivity in use of vildagliptin would be because of availability of adequate efficacy and safety data through various studies. 7,[19][20][21] Patients with T2DM are at 2-4 fold increased risk of cardiovascular morbidity and mortality compared to patients without T2DM. [22][23][24] One of the goals of the ADA/EASD recommendations is to make comprehensive cardiovascular (CV) risk reductions as a major focus of therapy.…”

Comparison of vildagliptin as an add-on therapy and sulfonylurea dose-increasing therapy in patients with inadequately controlled type 2 diabetes using metformin and sulfonylurea (VISUAL study): A randomized trial

“…Hypoglycemia was defined as symptoms suggestive of hypoglycemia and a self-monitored plasma glucose measurement <3.9 mmol/L. Severe hypoglycemia was defined as an episode that required assistance from another person or hospitalization with a plasma glucose measurement <3.1 mmol/L, as described [9,15,16]. Hypoglycemia documented at night while sleeping was defined as nocturnal hypoglycemia.…”

“…Vildagliptin improves glucose-dependent insulin secretion by increasing the GLP-1 levels, whereas sulfonylurea acts via a non-glucose-dependent mechanism through the sulfonylurea receptor [8]. Vildagliptin has shown significant glucoselowering efficacy with no clinically relevant weight gain as an add-on therapy in patients with T2DM inadequately controlled with metformin plus sulfonylurea [9]. In addition, the overall incidence of hypoglycemia is low with vildagliptin treatment because of its glucose-dependent action [10,11].…”