Brief reportVildagliptin more effectively achieves a composite endpoint of HbA1c < 7.0% without hypoglycaemia and weight gain compared with glimepiride after 2 years of treatment
Introduction
Although individualisation of treatment targets has become an important consideration in patients with type 2 diabetes (T2D) [1], achieving the glycaemic target of HbA1c < 7.0% (<53.0 mmol/mol) is recommended for most patients by current treatment guidelines to reduce the risk of long-term complications [2]. Hypoglycaemia [3] and weight gain [4], however, represent major limiting factors in getting patients to target.
Sulphonylureas (SUs) are often used in patients with T2D who do not achieve or cannot maintain glycaemic targets on metformin monotherapy. Although SUs have a well-established efficacy and overall safety profile, they can be associated with undesirable side effects including hypoglycaemia and weight gain [1], [2].
Vildagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that improves both α- and β-cell responsiveness to glucose [5]. Consequently, vildagliptin improves glycaemic control in patients with T2D, both as monotherapy or combination therapy, is associated with a low risk of hypoglycaemia, and is weight-neutral [6]. Vildagliptin and glimepiride were previously shown to provide comparable HbA1c-lowering efficacy as add-on therapy to metformin [7], [8].
In order to provide a more integrated assessment of the therapeutic benefit of vildagliptin, the present analysis evaluated a composite endpoint (CEP) defined as glycaemic control (HbA1c < 7.0% [<53.0 mmol/mol]), no hypoglycaemia and no weight gain, with the aim of comparing vildagliptin versus glimepiride as add-on therapy to metformin for the number of patients reaching this CEP. The present work also investigated whether there were differences in reaching the CEP in relationship to the age of patients and duration of diabetes.
Section snippets
Methods
This was a post hoc analysis of data from a 2-year, randomised, double-blind, active-controlled study comparing the addition of vildagliptin 50 mg b.i.d. and glimepiride (up-titrated to a maximum of 6 mg/day) in patients with T2D inadequately controlled (HbA1c 6.5–8.5% [48–69 mmol/mol]) on metformin monotherapy (≥1500 mg). Further details of the study design were reported by Matthews et al. [8].
A CEP of reaching HbA1c < 7.0% (<53.0 mmol/mol) with no hypoglycaemic events (HEs) (defined as symptoms with
Results
Of the 3118 randomised patients, 2062 patients with a baseline HbA1c ≥ 7.0% (≥53.0 mmol/mol) were included in this post hoc analysis (vildagliptin, n = 1051; glimepiride, n = 1011). Patient demographics and baseline characteristics were generally comparable between the two treatment groups (Table 1).
The overall proportion of patients achieving the CEP of HbA1c < 7.0% (<53.0 mmol/mol), with no hypoglycaemia and no weight gain, was higher in patients treated with vildagliptin (29.8%) than glimepiride
Discussion
It is increasingly recognised that, in addition to HbA1c reduction, controlling weight and avoiding hypoglycaemia are important treatment goals in the management of T2D [1].
To assess the overall clinical benefit, the present post hoc analysis measured the proportion of patients achieving the CEP of HbA1c < 7.0% (<53.0 mmol/mol) without hypoglycaemia and weight gain for vildagliptin and glimepiride in patients with T2D inadequately controlled on metformin monotherapy. The relative SR of achieving
Funding
This study was funded by Novartis Pharma AG.
Conflict of interest
The authors have a competing interest to declare. Giovanni Bader, Anja Schweizer and Parnia Geransar are employees of Novartis. Anja Schweizer and Parnia Geransar also owe shares to the company.
Acknowledgement
All authors participated in the development and writing of the paper and approved the final manuscript for publication. The authors take full responsibility for the content of the paper and thank Anuja Shah (Novartis Healthcare Pvt. Ltd.) for medical writing support, editorial assistance and collation and incorporation of comments from all authors.
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