Page 79 - Diamicron MR MIG Cycle 2(20-21) Final

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Table 2 – HEs in patients receiving gliclazide MR treatment.
n (%) Pre-Ramadan During Ramadan Post-Ramadan Total
(N = 1214) (N = 1212) (N = 1208) (N = 1214)
Patients with 1 symptomatic HE (confirmed or suggestive) 2 (0.2) 27 (2.2) 4 (0.3) 32 (2.6)
Patients with 1 confirmed HE (asymptomatic or symptomatic) 2 (0.2) 19 (1.6) 1 (<0.1) 21 (1.7)
Patients with 1 HE of any type 2 (0.2) 28 (2.3) 4 (0.3) 33 (2.7)
Patients with 1 severe HE 0 (0) 0 (0) 0 (0) 0 (0)
Data relating to the primary endpoint are highlighted in bold. Definitions of HEs are provided in the methods section.
HE, hypoglycaemic event; MR, modified release.

clamide provides irreversible inhibition of the Kir6.2/SUR1 fore continue with pre-Ramadan dosing levels during
K ATP channel, inhibition by gliclazide is rapidly reversible [17]. fasting. The observed reductions in HbA 1c , FPG and body
It is also important to note that the seasonal timing of weight are also consistent with other reports in the literature.
Ramadan and the dietary habits of patients choosing to fast Patients treated with metformin and gliclazide in the STEAD-
could potentially influence the risk of HEs. As Ramadan FAST study had an adjusted mean reduction in HbA 1c (0.03%),
occurs in the nine month of the lunar calendar, the fasting and body weight (1.1 kg) [12]. In the VIRTUE study, SU-treated
period passes through all seasons over a period of approxi- patients had an increase in 0.02% in HbA 1c values, but a
mately 35 years. While shorter fasts are expected in the win- decrease in weight of 0.13 kg [8]. When changing to an eve-
ter, longer fasts in the summer months are likely to ning dosing regimen during Ramadan, Zargar et al. showed
contribute to an increased risk of hypoglycaemia and dehy- that mean HbA 1c decreased by 0.8% and mean body weight
dration [18]. In 2019, the number of fasting hours during increased by 0.4 kg in gliclazide MR-treated patients [15].
Ramadan ranged between 13.5 and 15.5 h per day among Patients receiving gliclazide MR treatment during Ramadan
the nine countries. Another important observation was that are therefore able to maintain HbA 1c and body weight values
the majority of patients experiencing HEs reported eating while having a low risk of HEs.
2 meals per day on average during Ramadan. HEs occurred The data collected here have implications in other areas
at a mean (±SD) of 8.3 ± 4.7 h after the last food intake, high- such as intermittent fasting in patients with DM. Intermittent
lighting the importance of the pre-dawn meal (suhoor). fasting has been proposed as an alternative to calorie restric-
Therefore, dietary advice is crucial during the pre-Ramadan tion as a means to control body weight and improve car-
assessment. diometabolic health [20]. A recent systematic review and
While the majority of patients (approximately 60%) were meta-analysis concluded that intermittent fasting results in
able to complete their fast without a break, a small minority improvements to fasting blood sugar levels and insulin resis-
(62/1214 patients [5.1%]) broke their fast for more than three tance in patients with DM [21]. Patients with prediabetes fast-
consecutive days. Most patients broke their fast for more than ing according to a time-restricted feeding schedule exhibit
three days due to non-medical reasons (45/1214 [3.7%]). Non- improved insulin sensitivity and b-cell function, as well as
medical reasons, which can include travelling, menstruation, lower blood pressure, appetite and oxidative stress levels
and pregnancy/breastfeeding, can exempt followers from [22]. OADs that are suitable for use during periods of fasting
fasting during Ramadan. Only a small number of patients with low risk of hypoglycaemia are therefore valuable for
(3/1214 [0.25%]) broke their fast due to hypoglycaemia. the management of T2DM. This study confirms the safety of
According to IDF-DAR guidelines, high-risk patients should gliclazide MR even during extreme fasting periods such as
be encouraged to break their fast if self-measured blood glu- Ramadan, when rates of HEs are often higher than in the gen-
cose levels drop below 70 mg/dL or rise above 300 mg/dL [6]. eral population.
However, additional medical reasons could also trigger a The study has several limitations, including the biases that
patient to stop fasting. For example, symptoms of excessive are typically associated with observational study designs. In
dehydration and fatigue/dizziness were previously listed as addition, the study enrolled patients already receiving gli-
common reasons in the CRATOS study [19]. clazide MR at stable doses for 90 days prior to the inclusion
Changes in HbA 1c , FPG and body weight between V0 and visit. This suggests that the study drug was well tolerated in
V1 were assessed as secondary outcome measures in this these patients. Other relevant biases include underreporting
study. Patients included in the study generally had well- of adverse events and hypoglycaemic episodes, particularly
controlled blood glucose values at the inclusion visit and a those that were self-reported in patients’ diaries, as well as
large proportion of patients were receiving gliclazide MR recall bias.
monotherapy at baseline. While the overall goal of treatment One key strength of the present study is that it provides
during Ramadan is to allow patients with T2DM to maintain real-world evidence gathered by physicians treating a broad
glycaemic control and weight over the fasting period, results population of patients with T2DM according to their standard
presented here show that gliclazide-treated patients experi- clinical practice. A large number of patients were enrolled
enced a significant reduction in HbA 1c , FPG and body weight from a diverse range of institutions across nine countries
between study visits. As no dose changes were reported dur- from different regions, with various patterns of nutrition
ing the study, patients treated with gliclazide MR can there- and fasting during Ramadan. Treatment adherence was high