Effect of beinaglutide, a thrice-daily GLP-1 receptor agonist, on body weight and metabolic parameters: A systematic review and meta-analysis

Table 1 The basic characteristics of the included randomized controlled trials and participants

Registration no. and study place	Major baseline characteristics of the study subjects	Study arms	n	Age (years, mean ± SD)	Female (%)	Baseline body weight (kg, mean ± SD)	Baseline BMI (kg/m2, mean ± SD)	Duration of RCT
ChiCTR1900023428, Multicenter in China[19]	Adults with BMI ≥ 28 kg/m2 or BMI ≥ 24-27.9 kg/m2 with weight-related complication; No DM	Beinaglutide 0.2 mg s.c. TID	282	35.3 ± 9.1	51.4	89.35 ± 18.30	31.74 ± 4.60	16 weeks with a 12-week post-treatment observation
		Placebo	138	36.9 ± 8.7	52.9	88.04 ± 18.10	31.5 ± 4.70
ChiCTR1900023611, Single center in China[20]	Adults with T2D with HbA1c ≤ 9.5%; NAFLD, MRS showing IHTG ≥ 15%	Beinaglutide 0.1 mg s.c. TID	25	47.2 ± 13.0	48	85.2 ± 14.9	30.5 ± 4.0	24 weeks
		Lifestyle intervention	25	52.8 ± 15.2	40	87.4 ± 20.2	30.1 ± 4.7
NCT03593668, Single center in China[21]	Adults with BMI ≥ 28-37.5 kg/m2 or BMI ≥ 24-27.9 kg/m2 with weight-related complication; No DM	Beinaglutide 0.2 mg s.c. TID	32	32.5 ± 1 .6	50.0	94.0 ± 2.5	32.3 ± 0.4	12 weeks
		Metformin 0.5 gm orally TID	32	32.3 ± 1.4	56.3	88.0 ± 2.5	31.2 ± 0.6
ChiCTR2200061003, Single center in China[22]	Adults with T2D; BMI 22-40 kg/m2; At least 8 weeks of stable treatment with metformin alone (daily dose ≥ 1 g) prior to screening	Beinaglutide 0.1-0.2 mg s.c. TID + Metformin	67	52.1 ± 9.2	NA	84.34 ± 13.86	27.08 ± 3.64	6 months
		Insulin Aspart + Metformin	67	51.8 ± 8.3	NA	83.12 ± 16.09	26.87 ± 2.94
NCT03829891, Multicenter in China[23]	Adults with T2D for ≥ 6 months; HbA1c ≥ 7.5 - ≤ 11.0%; BMI 21-35 kg/m2; Stable OHA (alone or in combination therapy, excluding glinides, incretin-based therapies, and insulin) for ≥ 1 month	Beinaglutide 0.1-0.2 mg s.c. TID	35	52.6 ± 11.5	34.3	69.73 ± 14.45	24.71 ± 3.44	16 weeks, 8 weeks randomized period
		Insulin Glargine before bed	33	53.3 ± 8.13	21.2	72.36 ± 10.57	24.87 ± 2.48
ChiCTR2000033741, Single center in China[24]	Females with PCOS; Age 18-40 years; BMI ≥ 24 kg/m2	Beinaglutide 0.1-0.2 mg s.c. TID + Metformin 850 mg BID	32	26.75 ± 4.40	100	73.95 ± 6.71	28.65 ± 1.93	12 weeks
		Metformin 850 mg BID	32	25.43 ± 3.10	100	72.68 ± 6.23	28.79 ± 2.12

BID: Two times a day; BMI: Body mass index; DM: Diabetes mellitus; IHTG: Intrahepatic triglyceride; MRS: Magnetic resonance spectroscopy; NAFLD: Nonalcoholic fatty liver disease; OHA: Oral hypoglycemic agent; PCOS: Polycystic ovary syndrome; RCT: Randomized controlled trials; T2D: Type 2 diabetes; TID: Three times a day; s.c.: Subcutaneous injection; HbA1c: Glycated hemoglobin; SD: standard deviation; NA: Not available.

Table 2 The results of secondary efficacy outcomes findings in the meta-analysis

Outcome variables	No. of RCT included	No. of participants with outcome/participants analyzed		Pooled effect size, OR (95%CI)	I2 (%)	P value
		Beinaglutide arm	Control arm
Categorical
Subjects achieving BW reduction 5%	3	206/335	55/193	4.61 (3.07 to 6.93)	0	< 0.00001
Subjects achieving BW reduction 10%	3	80/335	12/193	5.34 (2.78 to 10.25)	0	< 0.00001
Continuous
SBP (mmHg)	3	349	203	-1.11 (-2.74 to 0.53)	0	0.19
DBP (mmHg)	3	349	203	-0.57 (-1.87 to 0.72)	0	0.38
FPG (mmol/L) in subjects without T2D	3	339	195	-0.11 (-0.26 to 0.04)	43	0.15
FPG (mmol/L) in subjects with T2D	3	107	108	0.32 (-0.50 to 1.15)	63	0.44
HbA1c (%) in subjects with T2D	3	107	108	0.05 (-0.27 to 0.38)	22	0.75
Fasting insulin (mIU/L) in subjects without T2D	2	309	165	-2.28 (-10.97 to 6.41)	69	0.61
HOMA-IR in subjects without T2D	3	339	195	-0.11 (-1.76 to 1.55)	70	0.9
ALT (U/L)	3	99	102	-4.31 (-11.87 to 3.24)	0	0.26
AST (U/L)	3	99	102	-2.65 (-8.11 to 2.81)	41	0.34
TC (mmol/L)	6	446	303	0.18 (-0.41 to 0.76)	95	0.55
LDL-C (mmol/L)	6	446	303	0.17 (-0.41 to 0.75)	99	0.56
HDL-C (mmol/L)	6	446	303	0.18 (-0.36 to 0.71)	99	0.52
TG (mmol/L)	6	446	303	0.16 (-0.43 to 0.75)	94	0.6
FFA (mmol/L)	2	331	190	0.54 (-0.54 to 1.61)	99	0.33

OR: Odds ratio; 95%CI: 95% confidence interval; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BW: Body weight; FFA: Free fatty acid; FPG: Fasting plasma glucose; HbA1c: Glycated hemoglobin; HDL-C: High-density lipoprotein cholesterol; HOMA-IR: Homeostatic model assessment for insulin resistance; TC: Total cholesterol; RCT: Randomized controlled trials; LDL-C: Low-density lipoprotein cholesterol; TG: Triglyceride; T2D: Type 2 diabetes.

Table 3 The results of safety outcome findings in the meta-analysis

Outcome variables	No. of RCT included	No. of participants with outcome/participants analyzed		Pooled effect size, RR (95%CI)	I2 (%)	P value
		Beinaglutide arm	Control arm
At least one AE	2	252/311	113/166	2.90 (0.28 to 30.29)	83	0.37
Serious AEs	2	8/350	1/205	1.80 (0.08 to 42.54)	55	0.71
Treatment discontinuation for any reason	5	36/198	29/196	1.22 (0.79 to 1.90)	0	0.37
Treatment discontinuation due to AEs	5	31/452	6/305	3.15 (1.32 to 7.54)	0	0.010
Nausea	5	191/417	27/270	4.51 (1.16 to 17.53)	87	0.03
Vomiting	4	77/382	2/237	8.19 (2.32 to 28.90)	15	0.001
Diarrhea	4	17/382	37 /237	0.27 (0.04 to 1.67)	63	0.16
Palpitation	2	18/325	2/180	3.95 (1.06 to 14.80)	0	0.04
Fatigue	3	19/357	4/212	2.53 (0.91 to 7.04)	0	0.08
Headache	4	36/382	6/237	2.87 (1.31 to 6.32)	0	0.009
Dizziness	3	76/350	7/205	6.07 (2.92 to 12.61)	0	< 0.00001
Upper RTI	3	28/350	14/205	0.99 (0.54 to 1.81)	0	0.98
Hypoglycemia	3	6/99	9/97	0.64 (0.2 to 1.92)	7	0.43

AE: Adverse event; RCT: Randomized controlled trial; 95%CI: 95% confidence interval; RR: Risk ratio; RTI: Respiratory tract infection.