|ISSN No. 1606-7754 Vol.15 No.2 August 2007|
The efficacy and safety of rosiglitazone with concurrent sulphonylurea therapy in subjects with type 2 diabetes mellitus in Nigeria
GC Onyemelukwe1, SS Wokoma2, AE Ohwovoriole3 and AG Bakari1
Department of Medicine, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria1, Department of Medicine, University of Port Harcourt Teaching Hospital, Port Harcourt , Nigeria3 and Department of Medicine, Lagos University Teaching Hospital, Lagos, Nigeria3
An open label study was conducted to asses the efficacy and safety of rosiglitazone when administered concurrently with sulphonylurea compounds. Sixty-three type 2 diabetic patients were enrolled in the study in three different centres across Nigeria, Zaria in the north, Lagos in the southwest and Port Harcourt in the southeast. Nigeria is a large country with multi-ethnic groups. Subjects were randomly divided into two treatment groups; one on only sulphonylurea and the other on rosiglitazone (4 mg daily) for 26 weeks in addition to the current dose of sulphonylurea. Fifty-two subjects (82.5%) completed the study. The addition of rosiglitazone to sulphonylurea therapy resulted in more steady control of fasting plasma glucose (FPG) over time, higher mean change in FPG from baseline and higher proportion of subjects recording HBA1C value of <7.5. There were no significant adverse events attributable to rosiglitazone therapy during the 26 weeks of therapy. It is concluded that the addition of rosiglitazone to sulphonylurea treatment is safe and has a synergistic effect in controlling glycaemia in type 2 diabetic patients. (Int J Diabetes Metab 15:61-66, 2007)
Key words: Rosiglitazone, sulphonylurea, type 2 diabetes, ethnic group, management
There has been a progressive increase in the incidence and prevalence of type 2 diabetes worldwide and this is particularly so in the underdeveloped and developing countries.1 Changes in lifestyles brought about by urbanization and modernization, as well as genetic factors are responsible for this change. In Nigeria, the national expert committee on non-communicable diseases estimates a national prevalence rate of 2.73% as of 1997, implying that not less than 1.05 million people aged 15 years and above had diabetes mellitus at that time.2 Even in suburban communities with relatively little urbanization, prevalence rates of as high as 1.6% have been reported.3
Considerable debate and controversy have been generated and still continue as to the initiating defect (insulin resistance or pancreatic beta-cell failure) that lead to the development of type 2 diabetes.4-5 Insulin resistance has been shown using the homeostasis model assessment method (HOMA)6 to characterise type 2 diabetic Nigerians who are found to be generally hypoinsulinaemic with advancement of the disease.7
Although the underlying pathogenic defect may vary between populations and most probably even within the same population, once type 2 diabetes has become established, the resultant hyperglycaemia is known to induce or aggravate insulin resistance.8-10 This is mediated through glucosamine, a product of glucose metabolism through the hexosamine pathway, which impairs the insulin-mediated translocation of GLUT4 glucose transporter in adipocytes and skeletal muscle.11
The thiazolidinediones are a class of oral anti-hyperglycaemic agents that specifically target insulin resistance and improve insulin sensitivity in skeletal muscle, liver and adipose tissue through the activation of peroxisome proliferators-activated receptor gamma (PPARγ)12 originally developed in the early 1980s in Japan as antioxidants.13 Controlled clinical trials assessing the efficacy of rosiglitazone as a single therapeutic agent in patients with type 2 diabetes showed an average decrease of fasting plasma glucose levels by about 45 mg/dl and of HbA1c by about 1.0%.14,15 This effect is dose-dependent, an effect that leveled off when daily doses were greater than 8 mg.
In many African centres, evaluation of control of diabetes using HBA1C is uncommon due to cost considerations and therefore fasting plasma glucose levels as well as the 2-h postprandial (2HPP) blood glucose levels have been used. The 2HPP could identify those with glucose spikes, a significant factor in the aetiopathogenesis of chronic diabetic complications.16 Investigations using micro-column technique for HbA1C17 showed that iron deficiency anaemia, sickle cell genotype as well as elevated blood urea conditions which must be determined and which are common in African diabetic patients may affect HBA1values. In some centres like Zaria, measurement of fructosamine values has been introduced.18
This study was therefore undertaken to study the efficacy and safety of the addition of rosiglitazone to sulphonylurea therapy in type 2 diabetic Nigerian patients with poor glycaemic control while on sulphonylurea monotherapy.