Safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with type 2 diabetes mellitus fasting during Ramadan: a systematic review and meta-analysis

Table 1 Baseline characteristics of individual studies and study participants included in the meta-analysis

Ref.	Study design, trial reg. number (if any)	Major inclusion criteria	Groups	GLD used	n	Sex	Age (years), mean (SD)	Duration of diabetes mellitus (years), mean (SD)	Baseline body weight (kg), mean (SD)	Baseline HbA1c (%), mean (SD)	Study duration
Azar et al[17], 2016, LIRA-Ramadan, 39 sites in 7 countries	Randomized, parallel-group, open-label, active-controlled trial, NCT01917656	Age 18-80 years, HbA1c 7%-10%, body mass index ≥ 20 kg/m2, on stable diabetes treatment (MFN ≥ 1 gm + SU MTD)	GLP-1RA	Liraglutide 18 mg + MFN	171	M: 85, F: 86	54.9 (9.27)	8.0 (5.26)	81.0 (17.1)	8.3 (0.94)	33 weeks
			Non- GLP-1RA	SU MTD + MFN	170	M: 83, F: 87	54.0 (9.33)	7.2 (4.39)	83.1 (16.0)	8.2 (0.91)
Hassanein et al[18], 2019, LixiRam, 16 sites in 5 countries	Phase 4, randomized, open-label, parallel-group, clinical trial, NCT02941367	Uncontrolled diabetes on SU + basal insulin ± one OAD	GLP-1RA	Lixisenatide 20 μgm + basal insulin + MFN	92	M: 40, F: 52	52.6 (9.5)	7.1 (4.8)	76.0 (14.6)	8.7 (0.7)	12-20 weeks
			Non-GLP-1RA	SU + basal insulin + MFN	92	M: 43, F: 49	54.1 (10.6)	7.4 (5.4)	75.0 (11.6)	8.5 (0.7)
Pathan et al[19], 2024, Pathan 2024, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders, Bangladesh	Open-label, single-center, two-arm parallel-group, prospective observational study	Age > 18 years, on stable GLDs for the last 3 months before enrolment	GLP-1RA	Semaglutide 0.5 mg ± OADs/insulin	55	M: 19, F: 36	49.05 (9.8)	7.34 (5.8)	N/A	7.43 (1.43)	24 weeks
			Non-GLP-1RA	OADs ± insulin, no semaglutide	75	M: 26, F: 49	53.04 (10.9)	12.37 (6.9)	N/A	8.10 (1.56)
Brady et al[20], 2014, Treat 4 Ramadan, 2 sites in United Kingdom	Randomized, parallel-group, open-label, active-controlled trial	Age ≥ 18 years, on stable dose of MFN or MFN + SU/Pioglitazone, HbA1c 6.5%-12%	GLP-1RA	Liraglutide 12 mg + MFN	52	M: 26, F: 26	52.2 (10.7)	N/A	79.0 (11.2)	7.8 (1.0)	16 weeks
			Non-GLP-1RA	MFN + SU	47	M: 24, F: 23	51.5 (11.1)	N/A	86.1 (16.9)	7.6 (1.1)

F: Female; GLD: Glucose-lowering drug; GLP-1RA: Glucagon-like peptide-1 receptor agonist; HbA1c: Glycated hemoglobin; M: Male; MFN: Metformin; MTD: Maximum tolerated dose; N/A: Not applicable; OAD: Oral antidiabetic drugs; SU: Sulfonylurea.

Table 2 Comparison of the safety outcomes in the glucagon-like peptide-1 receptor agonist vs non-glucagon-like peptide-1 receptor agonist arms

Outcome variables	Number of included studies	Number of participants with outcome/participants analyzed (%)		Pooled effect size, risk ratio (95%CI)	I2 (%)	P value
		GLP-1RA arm	Non- GLP-1RA arm
Any AE	3	54/311	50/314	1.07 (0.76-1.52)	0	0.69
Serious AE	2	2/263	0/262	4.97 (0.24-102.78)	N/A	0.30
AE leading to discontinuation of treatment	2	1/263	0/262	3.00 (0.12-72.70)	N/A	0.50
Gastrointestinal AEs	3	38/318	8/337	5.27 (1.40-19.89)	50	0.01
Heartburn	2	7/147	1/167	4.10 (0.25-68.20)	50	0.33
Nausea	3	17/318	1/337	14.05 (2.69-73.33)	0	0.002
Vomiting	2	9/263	1/262	5.96 (1.05-33.77)	0	0.04
Abdominal pain	2	3/147	0/167	4.61 (0.52-41.28)	0	0.17
Diarrhea	2	5/263	3/262	1.53 (0.40-5.87)	0	0.53
Any hypoglycemia	3	22/318	47/337	0.60 (0.19-1.90)	72	0.39
Documented symptomatic hypoglycemia	3	14/310	39/312	0.38 (0.16-0.88)	45	0.02

AE: Adverse events; GLP-1RA: Glucagon-like peptide-1 receptor agonists; N/A: Not applicable.