Efficacy and safety of tirzepatide in patients with type 2 diabetes mellitus: A meta-analysis

doi:10.3969/j.issn.1004-583X.2023.01.002

Abstract

Abstract:

Objective To systematically evaluate the efficacy and safety of tirzepatide in the treatment of type 2 diabetes mellitus (T2DM). Methods CNKI, Wanfang, VIP, Pubmed, Embase and Cochrane Library were retrieved to collect randomized controlled trails (RCTs), which met inclusion criteria. Results Seven RCTs representing 7163 T2DM patients were included. Meta-analysis results showed that the tirzepatide 5 mg, 10 mg and 15 mg was superior to the control groups (glucagon-like peptide-1 receptor agonist [GLP-1RA], insulin and placebo) in reducing glycosylated hemoglobin A1c (HbA₁c) and weight loss. The curative effect appeared to be highly dose-dependent, it showed greater efficacy with increasing dose. The decrease of HbA₁c in the tirzepatide 5 mg, 10 mg and 15 mg was ( $M D$ =-0.98, 95% $C I$ [-1.34, -0.62], ( $M D$ =-1.21, 95% $C I$ [-1.53,-0.89]) and ( $M D$ =-1.37, 95% $C I$ [-1.70,-1.03]), respectively. The weight loss ranges were ( $M D$ =-6.05, 95% $C I$ [-8.58,-3.52]), ( $M D$ =-8.56, 95% $C I$ [-11.14, -5.98]) and ( $M D$ =-10.60, 95% $C I$ [-13.24, -7.97]) (all $P$ <0.01), respectively. The tirzepatide 10 mg and 15 mg was superior to the control groups (GLP-1RA, insulin and placebo) in reducing fasting plasma glucose (FPG). The curative effect appeared to be dose-dependent, and the extent of FPG reduction with the tirzepatide 10 mg and 15 mg was ( $M D$ =-1.47, 95% $C I$ [-2.23, -0.70]) and ( $M D$ =-1.55, 95% $C I$ [-2.27, -0.83]), (all $P$ <0.01), respectively. The tirzepatide 5 mg was more effective in reducing FPG than placebo. No difference was significant in reducing FPG between tirzepatide 5 mg and the control group (GLP-1RA or insulin). There was also a dose dependence on the compliance rate of HbA₁c<7%, HbA₁c≤6.5%, HbA₁c<5.7% and the proportion of weight loss≥5%, weight loss≥10%, weight loss≥15%. However, there was no significant in compliance rate of HbA₁c and the proportion of weight loss increased. The safety of tirzepatide in incidence of hypoglycemia was similar to that of GLP-1RA and placebo, but lower than that of degludec/glargine insulin. The proportion of gastrointestinal adverse reactions of tirzepatide 5 mg, 10 mg and 15 mg was higher than that of placebo, the proportion of gastrointestinal adverse reactions of tirzepatide 10 mg and 15 mg was higher than that of the control group (GLP-1RA or insulin), but there was no significant difference in gastrointestinal adverse reactions between the control group and tirzepatide 5 mg. Conclusion Compared with placebo, GLP-1RA and insulin, tirzepatide has significant dose-dependent advantages in reducing HbA₁c, FPG and weight loss, and does not increase the risk of hypoglycemia, but tirzepatide 10 mg and 15 mg are associated with increased incidence of gastrointestinal adverse events.

Key words: diabetes mellitus, type 2, tirzepatide, meta-analysis

CLC Number:

R587.1

Xie Feifei, Zhang Weijian. Efficacy and safety of tirzepatide in patients with type 2 diabetes mellitus: A meta-analysis[J]. Clinical Focus, 2023, 38(1): 20-36.

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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2023.01.002

https://huicui.hebmu.edu.cn/EN/Y2023/V38/I1/20

Figures/Tables 31

Fig. 1 Flow chart of literature screening

Tab. 1 Basic information of included studies

纳入研究	干预措施	样本量(例)	年龄(岁)	HbA₁c(%)	疗程(周)	质量等级
Frias 2018^[2]	Tirzepatide 5 mg	55	57.9±8.2	8.2±1.0
	Tirzepatide 10 mg	51	56.5±9.9	8.2±1.1
	Tirzepatide 15 mg	53	56.0±7.6	8.1±1.1	26	B
	Dulaglutide 1.5 mg	54	58.7±7.8	8.1±1.0
	Placebo	51	56.6±8.9	8.0±0.9
Rosenstock 2021^[4]	Tirzepatide 5 mg	121	54.1±11.9	8.0±0.8
	Tirzepatide 10 mg	121	55.8±10.4	7.9±0.8	40	A
	Tirzepatide 15 mg	121	52.9±12.3	7.9±1.0
	Placebo	115	53.6±12.8	8.1±0.8
Frías 2021^[5]	Tirzepatide 5 mg	470	56.3±10.0	8.3±1.1
	Tirzepatide 10 mg	469	57.2±10.5	8.3±1.0	40	B
	Tirzepatide 15 mg	470	55.9±10.4	8.3±1.0
	Semaglutide 1 mg	469	56.9±10.8	8.3±1.0
Ludvik 2021^[6]	Tirzepatide 5 mg	358	57.2±10.1	8.2±0.9
	Tirzepatide 10 mg	360	57.4±9.7	8.2±0.9	52	B
	Tirzepatide 15 mg	359	57.5±10.2	8.2±0.9
	Insulin degludec	360	57.5±10.1	8.1±0.9
Del Prato 2021^[7]	Tirzepatide 5 mg	329	62.9±8.6	8.5±0.8
	Tirzepatide 10 mg	328	63.7±8.7	8.6±0.9	52	B
	Tirzepatide 15 mg	338	63.7±8.6	8.5±1.0
	Insulin glargine	1 000	63.8±8.5	8.5±0.9
Dahl 2022^[8]	Tirzepatide 5 mg	116	62±10	8.3±0.9
	Tirzepatide 10 mg	119	60±10	8.4±0.8	40	A
	Tirzepatide 15 mg	120	61±10	8.2±0.9
	Placebo	120	60±10	8.4±0.8
Inagaki 2022^[9]	Tirzepatide 5 mg	159	56.8±10.1	8.2±0.9
	Tirzepatide 10 mg	158	56.2±10.3	8.2±0.9	52	A
	Tirzepatide 15 mg	160	56.0±10.7	8.2±0.9
	Dulaglutide 0.75 mg	159	57.5±10.2	8.2±0.9

Fig. 2 Risk of bias plot of the studies

Fig. 3 Risk of bias summary chart of the studies

Fig. 4 Meta-analysis results of HbA1c

Fig. 5a Meta-analysis results of HbA1c in subgroups

Fig. 5b Meta-analysis results of Tirzepatide vs GLP-1RA or Insulin in subgroup

Fig. 5c Meta-analysis results of Tirzepatide vs Placebo in subgroup

Fig. 6 Meta-analysis results of FPG

Fig. 7a Meta-analysis results of FPG in subgroup

Fig. 7b Meta-analysis results of Tirzepatide vs GLP-1RA or Insulin in subgroup

Fig. 7c Meta-analysis results of Tirzepatide vs Placebo in subgroup

Fig. 8 Meta-analysis results of body weight

Fig. 9a Meta-analysis results of body weight in subgroup

Fig. 9b Meta-analysis results of Tirzepatide vs GLP-1RA in body weight subgroup

Fig. 9c Meta-analysis results of Tirzepatide vs Placebo in body weight subgroup

Fig. 10a Meta-analysis results of HbA1c<7% compliance rate

Fig. 10b Meta-analysis results of HbA1c<7% compliance rate in subgroup

Fig. 11a Meta-analysis results of HbA1c<6.5% compliance rate

Fig. 11b Meta-analysis results of HbA1c<6.5% compliance rate in subgroup

Fig. 12a Meta-analysis results of HbA1c<5.7% compliance rate

Fig. 12b Meta-analysis results of HbA1c<5.7% compliance rate

Fig. 13 Meta-analysis results of body weight loss >5%

Fig. 14 Meta-analysis results of weight loss >10%

Fig. 15 Meta-analysis results of body weight loss >15%

Fig. 16 Meta-analysis results of hypoglycemia events

Fig. 17 Meta-analysis results of gastrointestinal adverse reactions

Fig. 18a Meta-analysis results of gastrointestinal adverse reactions in subgroup

Fig. 18b Meta-analysis results of gastrointestinal adverse reactions in Tirzepatide vs GLP-1RA or Insulin in subgroup

Fig. 18c Meta-analysis results of gastrointestinal adverse reactions in Tirzepatide vs Placebo in subgroup

Fig. 19 Meta-analysis results of adverse reactions at the injection site

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