Patients and study design
This is an observational cohort study conducted at 11 different sites all across Pakistan on outpatient basis during Ramadan (May 2021–June 2021). The study included 132 patients with type 2 diabetes mellitus of ≥ 06 months duration. Eighty-eight patients received metformin and sitagliptin (100 mg/day sitagliptin dose), and 44 patients received metformin and empagliflozin (10 mg/day empagliflozin dose). Study participants were already taking these medications for at least six weeks prior to Ramadan.
Sample size estimation
It was estimated using online sample size calculator, openepi version 3.01 for mean difference, after input the change in mean HbA1c 8.2±1.5 % vs. 7.4±1.4% in Ramadan. We required at least n = 104 samples for this study, 52 samples per group, however due to expected drop out we are taking 130 samples per group and n=65 for this study.
Inclusion and exclusion criteria
Patients with HbA1c ranging from 6.5–8.5% before Ramadan and eGFR > 60 ml/min were included. Patients were excluded if they were on Insulin or had contraindications for fasting such as severe renal disease, liver diseases, unstable angina, history of diabetic ketoacidosis, hypoglycemic unawareness as per IDF diabetes and Ramadan (DAR) guidelines .
Clinical and laboratory workup
A detailed history followed by clinical examination was done in all patients fulfilling the inclusion criteria. Screening visit which was done at least 5 weeks prior to the start of Ramadan, the information regarding age, gender, history of diabetes, intention to fast in the forthcoming Ramadan, and diabetes related complications were obtained. Weight, height and blood pressure was taken. Body Mass Index (BMI) and blood pressure measurements were done before and after Ramadan. Each patient was provided individualized Ramadan specific education specially focusing on dietary modifications and frequent blood glucose monitoring by glucometer at different times of the day according to DAR IDF guidelines . Blood samples were collected to measure HbA1c, fasting blood glucose, urine DR and kidney function tests (serum creatinine & eGFR).
Patients were provided with a log book to record important daily events especially hypoglycemic symptoms, and whether they required any assistance due to symptoms of hypoglycemia, time and duration of hypoglycemia, and whether the fast was broken due to any reason. If patients experienced symptoms of hypoglycemia, they were instructed to check blood glucose level using glucometer and enter the readings in their log books along with symptoms.
The log book was maintained by the patients on a daily basis throughout Ramadan, irrespective of symptoms. In case of multiple episodes of hypoglycemia, each episode was documented separately. Furthermore, every patient was instructed to check blood glucose measurement before the evening meal three times per week.
At the end of Ramadan (i.e., study end), a follow up visit was done to obtain information regarding the fast-during Ramadan and any changes in medications dose and timing if required were done.
Safety and tolerability of these medications during Ramadan were assessed by reported adverse events entries in log book during the study period. All reported adverse events were categorized into mild, moderate or severe and relationship to study drug by the investigator. Patients were also contacted twice weekly by phone after the completion of Ramadan to find out about the occurrence of any serious side effect.
a) Hypoglycemic episodes during Ramadan were assessed by self-monitoring of the blood glucose during the day according to IDF diabetes and Ramadan (DAR) guidelines for blood glucose monitoring during Ramadan . The reported hypoglycemic symptoms in our study participants included palpitations, nausea, sweating, confusion, tremors, symptoms of dizziness, visual blurring, or intense hunger with or without biochemical confirmation. Blood glucose < 70 mg/dl on finger prick test was considered as hypoglycemia and it was considered severe episode if patient required assistance from another person or that resulted in seizure or loss of consciousness.
b) Dehydration episodes
This was assessed by symptoms of hypotension, orthostatic hypotension, postural dizziness, dehydration, syncope attack during fasting.
c) Genitourinary Infections
Number of participants who experienced any urinary tract or genital infections.
This included changes in weight and BMI after Ramadan.
The study protocol was approved by the local ethical committee and all patients signed informed consent before participation.
Results are presented as total count, percentages, mean and standard deviation. Comparison between categorical variables was done using chi-square test while numerical variables were compared using student t-test or Mann–Whitney U test. Values of weight, BMI, HbA1c and RBS were compared before and after fasting using Paired Sample T test. A P-value less than 0.05 was considered statistically significant. All statistical calculations were performed using SPSS 25 (IBM, USA).