Abstract
BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are widely used in managing type 2 diabetes (T2D). A significant number of these patients choose to observe religious fasting during Ramadan. Although existing guidelines recommend caution when administering SGLT2i during Ramadan due to potential adverse effects, there is limited data on their use in this patient population. AIM: To assess the safety and effectiveness of SGLT2i in patients with T2D who fast during Ramadan. METHODS: Relevant studies involving adults with T2D who received an SGLT2i in the intervention arm and other glucose-lowering drugs in the control arm were systematically searched through electronic databases. The primary outcome was the occurrence of adverse events in the two groups; additional outcomes included changes in glycemic and anthropometric parameters during the peri-Ramadan period. RevMan Web was used to conduct meta-analysis using random-effects models. Outcomes were presented as mean differences (MDs) or risk ratios (RRs) with 95%CI. RESULTS: Twelve studies involving 3625 subjects were included. The risks of postural dizziness (RR = 6.39, 95%CI: 1.58-25.80, P = 0.009, I (2) = 44%), hypotension/postural hypotension (RR = 4.43, 95%CI: 1.35-14.55, P = 0.01, I (2) = 31%), and sodium loss (MD = -1.00 mmol/L, 95%CI: -1.34 to -0.67, P < 0.00001, I (2) = 0%) were higher in the SGLT2i group compared to the non-SGLT2i group. The SGLT-2i group achieved larger reductions in systolic (MD = -2.41 mmHg, 95%CI: -4.52 to -0.30, P = 0.02, I (2) = 46%) and diastolic blood pressure (MD = -1.71 mmHg, 95%CI: -2.70 to -0.72, P = 0.0007, I (2) = 20%), and experienced a lower risk of symptomatic hypoglycemia (RR = 0.53, 95%CI: 0.29-0.97, P = 0.04, I (2) = 69%). The two groups exhibited comparable changes in glycated hemoglobin, body weight, and renal function. The risks of other specific adverse events, including dehydration, dizziness, volume depletion, symptomatic hyperglycemia, severe hypoglycemia, and genitourinary infections, were identical in the two groups. CONCLUSION: SGLT2i may be generally safe and effectively manage T2D during Ramadan; however, the results are less robust and should be interpreted with caution. Large multicenter randomized trials are necessary to confirm their safety, especially for at-risk groups, and to improve clinical decision-making.