Repaglinide versus glibenclamide treatment of Type 2 diabetes during Ramadan fasting

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Abstract

This study compared treatment with a prandial glucose regulator (repaglinide) and a sulphonylurea (glibenclamide) in Muslim Type 2 diabetic patients who practice Ramadan fasting. Two hundred and thirty-five patients, previously treated with a sulphonylurea, were randomised to receive either repaglinide (n=116, preprandially three-times daily) or glibenclamide (n=119, preprandially once- or twice-daily) 6 weeks before Ramadan. During Ramadan, patients changed their eating pattern to two meals daily, and the daily dose of repaglinide was redistributed to two preprandial doses. After Ramadan, patients resumed their regular meal pattern and treatment dosage for 4 weeks. During Ramadan, a statistically significant reduction in mean serum fructosamine concentration from baseline was observed in the repaglinide group (−16.9±4.9 μmol/l, −3.8%, P<0.05) but not the glibenclamide group (−6.9±4.8 μmol/l, −0.8%). Difference in change in HbA1c from baseline was not statistically significant between groups. The number of hypoglycaemic events with midday blood glucose <4.5 mmol/l was significantly lower in the repaglinide group (2.8%) than the glibenclamide group (7.9%) (P=0.001). Apart from hypoglycaemia, both treatments were equally well tolerated. Type 2 diabetic Muslims using prandial repaglinide showed a trend towards better glycaemic control and had a lower frequency of hypoglycaemia than patients using glibenclamide during Ramadan.

Introduction

Repaglinide (NovoNorm® [Prandin® in the USA, Gluconorm® in Canada]) is a novel insulin secretagogue with a rapid onset and relatively short duration of action [1], [2], [3] developed for the role of prandial glucose regulation (PGR). The PGR principle is to provide insulin when needed by stimulating endogenous insulin secretion in response to food intake. Repaglinide is designed to be taken with each main meal, if and when eaten, to prevent excessive postprandial glucose excursion. The antidiabetic efficacy of PGR with repaglinide has been demonstrated in placebo-controlled studies [4], [5], [6], in which markers of glycaemic control were significantly improved compared with placebo. Temporal improvements in glycaemic control have also been shown in comparative trials with other oral antidiabetic agents: repaglinide provides a level of glycaemic control at least as equivalent to that obtained with sulphonylureas (SUs) [7], [8], [9], [10] or metformin [11], and superior to troglitazone [12].

Meal-associated treatment with repaglinide is well tolerated irrespective of the number of meals consumed in a day [13]. Furthermore, in well-controlled Type 2 diabetic patients who miss or delay a meal it reduces the risk of hypoglycaemia compared with longer-acting SUs (e.g. glibenclamide [glyburide in the USA]) [14]. The timing and number of main meals can be chosen on a day-by-day basis, with fewer restrictions being placed upon the patient's daily schedule. PGR also reduces the patient's dependency on snacks, making it easier to control energy intake and, in turn, maintain or reduce body weight [15], [16].

Ramadan is a basic principal of Islam strictly observed by its followers, during which all healthy adult Muslims fast daily from dawn to sunset for 1 month. Set according to the lunar calendar, the dates of observance differ each year and the period of fasting also varies by geographical location and season, lasting up to 18 h or more in summer months and northern latitudes. During the fast, the individual must abstain not only from food and drink but also from oral medication [17]. At night, food and fluids may be consumed freely, often leading to increased intake of drinks with high sugar content and sweet foods which are specially prepared during this period [18]. These pose an obvious problem for diabetic patients, who mostly prefer not to accept the exemptions allowed by Islam for patients with serious disease [17]. In Type 2 diabetic patients treated with a SU, changes in treatment regimen with regard to type, dosage and/or timing of intake are necessary to reduce the risk of hypoglycaemia. The largest published study involving 591 patients treated with glibenclamide during Ramadan reported similar increases in glycated haemoglobin in groups of patients who practiced or abstained from fasting [19]. The purpose of this study was to compare glycaemic control in Muslim Type 2 diabetic patients treated with repaglinide or glibenclamide during Ramadan.

Section snippets

Patients

The trial population comprised Muslim patients with Type 2 diabetes (according to WHO criteria) who practised Ramadan fasting. Prior to enrolment into the study, patients were required to have been treated with SU (either alone or in combination with metformin or acarbose) for at least 6 months. Patients were excluded from the trial if they had cardiac disease (congestive heart failure, angina pectoris, previous myocardial infarction); impaired kidney or liver function; severe uncontrolled

Patient population

A total of 235 patients were randomised and received repaglinide (116 patients) or glibenclamide (119 patients). One hundred and ninety-seven (84%) patients completed the trial in accordance with the protocol. The reasons for discontinuation were non-compliance with protocol (16 patients), withdrawals due to adverse events (six patients), ineffective therapy (ten patients) and other reasons (six patients).

Demographic data for the patients are presented in Table 1. Generally, the trial

Discussion

The present trial compared monotherapy with repaglinide and glibenclamide in Muslims with Type 2 diabetes during Ramadan. The patients had borderline-to-poor glycaemic control at baseline. The majority had longish duration of diabetes and all had been receiving SU or SU combined with metformin or acarbose before trial entry.

Recent clinical trials have shown that repaglinide provides an equivalent level of glycaemic control to that obtained with glipizide [7] and glibenclamide [8], [9] in

Acknowledgements

This project was supported by Novo Nordisk Asia Pacific Pte Ltd., Singapore. Author list for The Ramadan Study Group: Malaysia—Prof. Mafauzy M., School of Medical Sciences, Univeristi Sains Malaysia, Kelantan, Associate Prof. S.P. Chan, Universiti Hospital, Kuala Lumpur, Dr. K. Norshinah, Department of Medicine, Hospital Kuala Lumpur, Dr. Dato’ S. Kumari, Hospital Tenku Ampuan Rahimah, Klang, Prof. Dato’ Mustaffa E., Seremban Hospital, Negri Sembilan; UK—Dr. C. Kesson, The Diabetic Clinic,

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    Major data published in abstract form only: American Diabetes Association 61st Scientific Sessions, Philadelphia, PA, 22–26 June, 2001; and European Association for the Study of Diabetes 37th Annual Meeting, Glasgow, UK, 9–13 September, 2001 (Embong on behalf of the Ramadan Study Group, Diabetes 50(2) (2001) A434; Mafauzy on behalf of the Ramadan Study Group, Diabetologia 44(Suppl. 1) (2001) A60).

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    on behalf of The Ramadan Study Group.

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