Real-life efficacy and safety of vildagliptin compared with sulfonylureas as add-on to metformin in patients with type 2 diabetes mellitus in Germany

Abstract

Objective:

Metformin is an established first-line treatment for type 2 diabetes mellitus (T2DM) patients, but intensification of oral anti-diabetes therapy is usually required over time. A large observational study of 45,868 T2DM patients in 27 countries (EDGE) was conducted to compare the effectiveness and safety of vildagliptin as add-on therapy to another oral anti-diabetes drug (OAD) vs other dual OAD combinations. This report presents results from a post-hoc analysis of patients in Germany who received vildagliptin or a sulfonylurea (SU) in combination with metformin.

Research design and methods:

Patients inadequately controlled with monotherapy became eligible only after the add-on treatment was finalized. Patients included were assigned to receive either vildagliptin or another OAD (SUs, thiazolidinediones, glinides, α-glucosidase inhibitors, or metformin; DPP-4 inhibitors or glucagon-like peptide-1 [GLP-1] mimetics/analogs were excluded). The primary end-point was the proportion of patients achieving a reduction in HbA1c >0.3% without peripheral edema, hypoglycemia, discontinuation due to gastrointestinal event, or weight gain ≥5%.

Results:

Of 8887 patients enrolled in Germany, 6439 received vildagliptin and 971 received SUs as add-on to metformin. The primary end-point was reached in 34.9% and 29.6% of patients in the vildagliptin and SU groups, respectively, with an unadjusted odds ratio of 1.27 (95% CI = 1.09, 1.47; p = 0.001). HbA1c decreased in both cohorts from baseline (−0.7% with vildagliptin vs −0.5% with SUs), with a mean between-group difference of −0.2% (95% CI = −0.22, −0.09). The number of hypoglycemic events was 4-fold higher in the SU group than in the vildagliptin group (vildagliptin = 0.11%; SU = 0.41%).

Conclusions:

In a real-life setting, vildagliptin was associated with a numerically greater reduction in HbA1c, less hypoglycemia, and more patients reaching target HbA1c without hypoglycemia or weight gain compared with SUs. Open-label design and under reporting of adverse events are limitations of this post hoc analysis.

Key words::

• Observational
• Real-life
• Responder rate
• Vildagliptin
• Sulfonylurea

Transparency

Declaration of funding

The study was funded by Novartis Pharma AG, Basel, Switzerland.

Declaration of financial/other relationships

RG has received fees for consultancy, advisory boards, speaking, travel or accommodation from AstraZeneca, Bayer, Berlin-Chemie, BMS, Eli Lilly, MSD, Novartis, Sanofi-Aventis, Roche and UCB; J-BG, GB, and MD are all employees of Novartis. CMRO Peer Reviewers on this manuscript have received an honorarium from CMRO for their review work. Peer reviewer 1 has disclosed that he is the recipient of research/grant funding from GSK, Novartis, Novo-Nordisk, Takeda, Astra-Zeneca, NIH, sanofi-aventis, Eli Lilly, and Daiichi-Sankyo; is a consultant to, and lecturer for, GlaxoSmithKline, Novartis, Takeda, sanofi-aventis, Eli Lilly, and Daiichi Sankyo; and is on the speakers bureau for Novo Nordisk and sanofi-aventis. Peer Reviewer 2 has no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Lakshmi Deepa, Novartis Healthcare Private Limited, for medical writing support. Previous presentation: Parts of the data have been presented at the 73rd Scientific Sessions of the American Diabetes Association, 21–25 June 2013, Chicago, IL; 48. Jahrestagung Deutsche Diabetes-Gesellschaft, May 8–11, 2013, Stuttgart, Germany.