Diabetes management throughout the fasting month of Ramadan is a delicate and difficult matter. Indeed, the majority of Muslims with diabetes continue to fast despite medical advice to the contrary [11, 12]. However, there are significant hazards that fasting may entail [13].
Patients with diabetes who are at high or very high risk are recognized to be susceptible to hypoglycemia (especially during the day), undetected hyperglycemia (especially at night), dehydration, and DKA (especially at night) during the fasting period of Ramadan [14]. Hence, it is critical to choose an antidiabetic drug that is supported by scientific data and does not typically induce hypoglycemia, which would need the patient to interrupt their fast [15].
It has been demonstrated that SGLT2i is safe and effective when used in conjunction with other oral hypoglycemic agents, metformin, and intensive insulin treatment in several randomized controlled trials [16–19].
To the best of our knowledge, after intensive literature reading this is the first study to assess the efficacy and safety of the first use of SGLT2i during Ramadan fasting. The existing studies primarily focus on using SGLT2i before Ramadan fasting [16, 20, 21].
Our results revealed that the differences in weight and BMI between during Ramadan and after Ramadan were not statistically significant. Systolic Blood Pressure (SPB) and Diastolic Blood Pressure (DPB) were significantly lower after Ramadan compared to during Ramadan. Both HbA1c levels and creatinine levels were significantly lower after Ramadan than during Ramadan. GFR was significantly higher after Ramadan than during Ramadan. Interestingly, for patients suffering from IHD, HTN, PN, and CKD, HbA1c was significantly lower after Ramadan than during Ramadan.
In disagreement with our results, Sheikh et al. [22] noted that eGFR was significantly lower after Ramadan than pre-Ramadan. Also, SBP, DBP, HbA1c, and creatinine were comparable after Ramadan to pre-Ramadan. This difference may be attributed to the small sample size, 63.4% of the patients received empagliflozin, and patients with eGFR < 45 ml/min/1.73 m2 were excluded.
In contrary, Ahmed et al. [21] stated that SPB and DPB were insignificantly different between pre-Ramadan and after-Ramadan. This difference may be attributed to performing their study on patients with HbA1c ranging from 6.5–8.5% before Ramadan and eGFR > 60 ml/min.
However, Pathan et al. [23] found that creatinine and eGFR were insignificant between after Ramadan and before Ramadan. This difference may be attributed to that all subjects who had an eGFR of less than 45 ml/min/1.73 m2 were excluded from the research.
In contrast with our results, Abdelgadir et al. [20] noticed that SPB and DPB had insignificant differences between during Ramadan and after Ramadan. Creatinine and eGFR were higher after Ramadan than during Ramadan. This difference may be attributed to the use of a flash glucose monitoring system in blood glucose level management and monitoring, in which a sensor is applied on the upper arm. The sensor estimated glucose levels using the interstitial fluid under the skin records accurate glucose levels 24 hrs. a day. Every few minutes the sensor records glucose levels, 24 hours a day giving more accurate results [24].
In agreement with our results, Gad et al. [25] conducted a systematic review and meta-analysis that included five studies to evaluate the effects of Ramadan fasting on patients with T2DM treated with SGLT2i and showed that weight was insignificantly different between before Ramadan and after Ramadan, DPB and HbA1c were significantly lower after Ramadan than before Ramadan.
Also our results were supported Sheikh et al. [22] who noted that in T2DM using SGLT2i, the weight was insignificantly different between pre-Ramadan and after Ramadan.
Regarding weight, BMI, and HbA1c study performed by Ahmed et al. [21] was in consistent with our findings.
Additionally, Pathan et al. [23] found that similar results of weight SBP, DBP (correct them, not SPB or DPB) and A1c in their study participants on empagliflozin.
Moreover, Abdelgadir et al. [20] noticed that in T2DM using the SGLT2i group, weight was insignificant between before Ramadan and after Ramadan. HbA1c was lower after Ramadan than before Ramadan.
In the present study, there was a significant negative correlation between age and HbA1c after Ramadan (r=-0.267, P = 0.037), eGFR during Ramadan (r = -0.667, P < 0.001), and eGFR after Ramadan (r =-0.684, P < 0.001).
HbA1c levels after Ramadan reflected the average blood glucose control over the previous two to three months, including the fasting month. The age at which patients begin using SGLT2i could reflect the duration and progression of their diabetes condition [26]. Older patients might have more prolonged exposure to high glucose levels and potentially more complications or a longer history of diabetes management strategies [27]. Starting SGLT2i later might suggest a switch or addition in therapy, possibly reflecting a more aggressive approach to controlling HbA1c levels that were not adequately managed with previous therapies. SGLT2i at an older age is associated with better after Ramadan glycemic control [28].
Also, kidney function naturally declines with age due to physiological changes, reduced renal blood flow, and nephron loss. Older individuals are more likely to have pre-existing reduced eGFR, and thus the impact of SGLT2i affecting the kidneys might be more pronounced [29, 30].
As limitations, the study performed was in a single center. Patients combine SGLT2i with insulin and secretagogues when fasting before Ramadan, so, further studies are necessary on patients receiving SGLT2i in combination with other oral hypoglycemic agents. Further studies comparing SGLT2i with other drugs are needed. Further studies to assess SGLT2i safety and efficacy in the long run.