Clinical evaluation of combined therapy for type 2 diabetes

Abstract

Objective:

Therapeutic guidelines recommend the combination of drugs as necessary to control type 2 diabetes (T2D). This research assessed the effectiveness of pioglitazone (Pio), metformin (Met) and sulfonylurea (SU) combinations in the routine clinical practice.

Research design and methods:

A nationwide, 12-month prospective, observational cohort study was performed in 2294 patients with T2D (50.3% females, mean age: 61.1 years, mean body mass index: 30.2 kg/m², mean time since diagnosis: 8.5 years) who started, at the discretion of treating physician, oral antihyperglycaemic treatment with either Pio + SU, Pio + Met or SU + Met because of inadequate control with previous therapy. Fasting plasma glucose (FPG), glycohaemoglobin (HbA1c), lipids, blood pressure, and anthropometric parameters were measured, and 10-year cardiovascular risk was estimated.

Results:

FPG, HbA1c and total cholesterol at baseline had mean values (184.6 mg/dl, 8.5% and 246.0 mg/dl, respectively) associated with an excess of micro- and macrovascular risk. The mean changes from baseline in the Pio + SU, Pio + Met and SU + Met cohorts were, respectively, −37.9, −32.7 and −25.8 mg/dl for FPG; −1.1, −1.0 and −0.7% for HbA1c; −30.7, −38.7 and −17.1 mg/dl for triglycerides; and +2.3, +2.5 and +0.6 mg/dl for HDL cholesterol. In consequence, the estimated 10-year cardiovascular risk decreased more in the Pio cohorts, particularly with Pio + Met (1.7% versus 1.4% Pio + SU and 1.0% SU + Met –Framingham equation– and 0.6% versus 0.4% SU + Met – Systematic Coronary Risk Evaluation model–). Related adverse events were significantly (p = 0.016) more frequent in Pio cohorts (4.7% with Pio + SU, 5.1% with Pio + Met) than in the SU + Met cohort (2.4%).

Conclusions:

In patients with T2D failing therapy, mostly SU or Met monotherapy, pioglitazone add-on treatment was associated with a significant improvement of micro- and macrovascular risk estimations. These results from real-life clinical conditions support the findings of prior randomised trials, although they should be interpreted with caution because of the observational, nonrandomised design.

Key words::

• Epidemiologic studies
• Hyperlipidaemia
• Hypoglycaemic agents
• Insulin resistance
• Pioglitazone

Transparency

Declaration of funding

This clinical trial has been funded by Lilly Research Laboratories, Alcobendas, Spain.

Declaration of financial/other relationships

Á.R., P.P. and J.R. have disclosed that they are full-time employees of Lilly or any of its affiliates. L.C and S.T. have disclosed that they have received fees from Lilly as clinical investigators. In addition S.T. has received honoraria from Lilly as a speaker.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgements

The authors thank Medicxact, which acted as an external Medical Writing services provider and, in particular, Jesús Villoria who drafted the manuscript and provided technical and editorial assistance.

P.P. acted as statistical expert for this study.

Interim (6-months) results of this clinical study have been published previously48.