Safety and efficacy of sodium-glucose cotransporter-2 inhibitors in adults with type 2 diabetes fasting during Ramadan: A meta-analysis

Table 1 Baseline characteristics of individual studies and study participants included in the meta-analysis, mean (SD)/median (interquartile range)

Ref.	Study design	Major inclusion criteria	Groups	Glucose-lowering drug used	Number	Sex	Age (years)	Duration of diabetes mellitus (years)	Baseline body weight (kg)	Baseline HbA1c (%)	Study duration
Abdelgadir et al[16], 2019, United Arab Emirates	Prospective interventional	Age 18-75 years, all using insulin	SGLT2i	SGLT2i + insulin ± other OADs	49	Male: 19, female: 30	57.5 (9.1)	NA	82 (13.9)	7.95 (1.1)	14 weeks
			Non-SGLT2i	Insulin+ OADs other than SGLT2i	46	Male: 16, female: 36	55.4 (9.4)	NA	85 (11.1)	7.7 (1.0)
Ahmed et al[17], 2022, Pakistan	Prospective, observational	HbA1c 6.5%-8.5%, eGFR > 60 mL/minute/1.73 m2	SGLT2i	Metformin + empagliflozin	44	Male: 24, female: 20	44.7 (10.7)	NA	85.3 (7.8)	7.2 (0.8)	9 weeks
			Non-SGLT2i	Metformin + sitagliptin	88	Male: 43, female: 45	50.6 (10.5)	NA	77.6 (13.7)	7.8 (1.5)
Gameil et al[18], 2022, Egypt	Case-control observational	Age 45-60 years, HBA1c 7.5%-8.8%, body mass index > 25 kg/m2, eGFR > 60 mL/minute/1.73 m2	SGLT2i	Empagliflozin ± OAD/glargine	87	Male: 58, female: 29	52.4 (6)	5 (2-9)	89.6 (14.6)	7.9 (0.5)	NA
			SGLT2i	Dapagliflozin ± OAD/glargine	85	Male: 54, female: 31	52.5 (6.3)	6 (2-8)	92.5 (13.2)	8.1 (0.4)
			Non-SGLT2i	OAD other than SGLT2i ± basal insulin	73	Male: 48, female: 25	52.3 (6)	5 (2-9)	93.4 (12.1)	8.3 (0.5)
Goh et al[19], 2023, Malaysia	Prospective cohort	Age 18-75 years, eGFR > 30 mL/minute/1.73 m2	SGLT2i	Empagliflozin ± OAD/insulin	48	Male: 12, female: 36	48.0 (43.5-56.5)	10.5 (6-15)	77.7 (66.7-99.2)	8.4 (7.25-9.85)	6 weeks
			Non-SGLT2i	OAD except SGLT2i ± insulin	50	Male: 16, female: 34	51.5 (42-58)	4.5 (2-10)	75.3 (69.4-84.1)	8.1 (6.60-10.30)
Hassanein et al[20], 2017, Lebanon, Kuwait, and the United Arab Emirates	Non-randomised, parallel-cohort, prospective, comparative	Age 18-65 years, HbA1c ≤ 8.5%	SGLT2i	Canagliflozin + metformin ± DPP4i	162	Male: 100, female: 62	52.3 (7.7)	6.5 (5.9)	87.1 (14.8)	7.3 (0.8)	8 weeks
			Non-SGLT2i	Sulfonylurea + metformin ± DPP4i	159	Male: 87, female: 72	54.3 (7.4)	7.6 (5.5)	82.1 (14.1)	7.2 (0.8)
Hassanein et al[21], 2024, nine countries	Prospective, real-world, observational	Age ≥ 18 years	SGLT2i	iGlarLixi + SGLT2i use, with or without other OADs	174	Male: 98, female: 76	55.2 (9.6)	11.4 (6.3)	87.9 (16.2)	8.2 (1.3)	3-5 months
			Non-SGLT2i	iGlarLixi with or without other OADs	246	Male: 134, female: 112	58.4 (9.8)	12.6 (6.4)	85.5 (14.0)	8.2 (1.0)
Pathan et al[22], 2022, Bangladesh	Multi-centre, open-label, two-arm parallel-group study	Age >18 years, HbA1c 7%-10%, eGFR > 45 mL/minute/1.73 m2	SGLT2i	Empagliflozin + metformin± DPP4i	274	Male: 134, female: 140	49.0 (11.8)	7.8 (5.9)	70.7 (11.3)	8.4 (1.45)	24 weeks
			Non-SGLT2i	Metformin ± DPP4i	219	Male: 95, female: 124	49.7 (10.5)	6.3 (4.8)	66.4 (9.5)	8.1 (1.46)
Pathan et al[23], 2025, Bangladesh	Real-life experience study	Age ≥ 18 years, type 2 diabetes mellitus for at least 1 year, HbA1c < 10%	SGLT2i	Ertugliflozin ± OAD	703	Male: 276, female: 419	50.21 (11.11)	6.74 (5.39)	69.93 (11.54)	8.16 (0.91)	8 weeks
			Non-SGLT2i	OAD except ertugliflozin	670	Male: 281, female: 387	50.53 (11.17)	5.75 (4.46)	68.74 (10.53)	7.79 (0.87)
Samkari et al[24], 2023, Saudi Arabia	Prospective cohort study	Age 18-70 years, eGFR > 60 mL/minute/1.73 m2	SGLT2i	Empagliflozin + OAD	77	Male: 33, female: 44	56 (51-62)	9.00 (5.00-15.00)	NA	7.80 (7.10-8.77)	12 weeks
			Non-SGLT2i	Sulfonylurea and metformin ± DPP4i	77	Male: 35, female: 42	52 (47-64)	7.00 (5.00-15.00)	NA	7.50 (6.70-8.33)
Shao et al[25], 2018, Singapore	Prospective observational controlled cohort	Age 21-75 years, eGFR > 45 mL/minute/1.73 m2	SGLT2i	SGLT2i ± OAD/insulin	35	Male: 19, female: 16	49.9 (10.6)	15.7 (8.3)	88.2 (24.1)	9.3 (1.9)	NA
			Non-SGLT2i	OAD/insulin except SGLT2i	33	Male: 18, female: 15	54.7 (11.2)	12.3 (6.0)	73.9 (19.1)	8.7 (1.6)
Wan Seman et al[26], 2016, Malaysia	Randomized, open-label	Age 18-65 years, HbA1c 7%-10.5%	SGLT2i	Dapagliflozin + metformin	58	Male: 35, female: 23	53 (9.1)	5.0 (3.0- 9.0)	77.5 (13.9)	7.7 (7.08- 8.43)	12 weeks
			Non-SGLT2i	Sulfonylurea + metformin	52	Male: 31, female: 21	56 (9.1)	6.0 (3.0- 10.3)	75.6 (15.35)	7.6 (6.9-8.1)
Yousuf et al[27], 2022, Pakistan	Prospective case-control observational	Age 18-65 years, HbA1c < 8.5%	SGLT2i	Empagliflozin + metformin ± DPP4i	58	Male: 30, female: 28	52.1 (10.63)	6.98 (5.08)	NA	7.74 (0.89)	14 weeks
			Non-SGLT2i	Sulfonylurea + metformin ± DPP4i	58	Male: 31, female: 27	50.43 (9.23)	5.84 (5.82)	NA	7.9 (0.83)

DPP4i: Dipeptidyl peptidase-4 inhibitor; eGFR: Estimated glomerular filtration rate; HbA1c: Glycated hemoglobin; NA: Not available; OAD: Oral antidiabetic drug; SGLT2i: Sodium-glucose cotransporter-2 inhibitors.

Table 2 Comparison of the safety outcomes in the sodium-glucose cotransporter-2 inhibitor vs non- sodium-glucose cotransporter-2 inhibitor arms

Outcome variables (categorical)	Number of included studies	Number of participants with outcome/participants analyzed (%)		Pooled effect size	I2 (%)	P value
		SGLT2i arm	Non-SGLT2i arm
Any AE, RR (95%CI)	3	71/397	53/462	1.40 (0.83-2.39)	59	0.21
Serious AE, RR (95%CI)	2	1/220	0/211	2.74 (0.11-68.72)	Not available	0.54
Hospitalization, RR (95%CI)	2	2/135	0/129	2.84 (0.30-26.98)	0	0.36
Abdominal pain, RR (95%CI)	3	9/805	9/816	1.55 (0.62-3.88)	0	0.35
Dehydration, RR (95%CI)	5	64/1042	30/1050	1.79 (0.83-3.83)	58	0.14
Dizziness, RR (95%CI)	4	21/971	32/937	0.66 (0.10-4.21)	81	0.66
Postural dizziness, RR (95%CI)	5	65/427	4/396	6.39 (1.58-25.80)	44	0.009
Hypotension/postural hypotension, RR (95%CI)	7	61/1265	4/1195	4.43 (1.35-14.55)	31	0.01
Volume depletion, RR (95%CI)	4	40/571	33/513	1.34 (0.62-2.90)	54	0.46
Headache, RR (95%CI)	4	10/445	14/518	0.90 (0.38-2.14)	5	0.81
Hunger, RR (95%CI)	3	10/268	20/267	0.33 (0.04-2.78)	74	0.31
Sweating, RR (95%CI)	2	8/210	6/209	1.38 (0.51-3.78)	0	0.53
Generalized weakness, RR (95%CI)	4	22/326	27/319	0.58 (0.14-2.45)	54	0.46
Symptomatic hyperglycemia, RR (95%CI)	4	29/356	39/474	0.81 (0.54-1.20)	0	0.29
Increased urination, RR (95%CI)	4	23/322	14/357	2.15 (0.81-5.70)	16	0.12
Symptomatic hypoglycemia, RR (95%CI)	10	56/1640	135/1646	0.53 (0.29-0.97)	69	0.04
Severe hypoglycemia, RR (95%CI)	3	0/375	8/435	0.14 (0.02-1.11)	0	0.06
Genital infection, RR (95%CI)	4	7/326	3/319	2.03 (0.23-17.59)	47	0.52
Urinary tract infection, RR (95%CI)	5	15/1241	15/1188	1.18 (0.53-2.60)	0	0.69
Broke fast, RR (95%CI)	2	8/126	14/123	0.38 (0.03-5.26)	70	0.47
Number of days fasted, MD (95%CI)	3	252	296	-0.26 (-1.72 to 1.21)	88	0.73
Serum urea (mmol/L), MD (95%CI)	2	83	83	0.67 (-0.52 to 1.87)	86	0.27
Serum creatinine (mg/dL), MD (95%CI)	5	485	423	0.03 (-0.05 to 0.11)	64	0.43
Estimated glomerular filtration rate (mL/minute/1.73 m2), MD (95%CI)	7	1311	1189	-0.81 (-1.83 to 0.20)	0	0.12
Serum sodium (mmol/L), MD (95%CI)	3	1012	922	-1.00 (-1.34 to -0.67)	0	< 0.00001
Serum potassium (mmol/L), MD (95%CI)	3	1012	922	0.01 (-0.17 to 0.19)	51	0.89

AE: Adverse events; MD: Mean difference; RR: Risk ratio; SGLT2i: Sodium-glucose cotransporter-2 inhibitors.