Renal effects and safety of tirzepatide in subjects with and without diabetes: A systematic review and meta-analysis

Table 1 Summary of the safety outcome findings

Outcome variables	Control group	Tirzepatide dose	No. of participants with outcome/participants analyzed		Pooled effect size, RR (95%CI)	I2 (%)	P value
			Tirzepatide arm	Control arm
Renal events	Placebo	Pooled	12/3180	2/1553	2.00 (0.61-6.55)	0	0.25
		10 mg	5/1018	2/1027	2.51 (0.48-12.96)	0	0.27
		15 mg	5/1552	2/1553	1.83 (0.48-6.89)	0	0.37
UTI	Placebo	Pooled	28/2980	20/1223	0.76 (0.42-1.36)	0	0.35
		5 mg	5/848	4/862	1.10 (0.28-4.33)	5	0.90
		10 mg	5/923	5/931	0.97 (0.31-3.03)	0	0.96
		15 mg	18/1209	20/1223	0.81 (0.43-1.54)	0	0.52
	Insulin	Pooled	3/2399	4/1928	0.54 (0.07-4.19)	37	0.56
		5 mg	1/802	4/1928	1.03 (0.13-7.84)	22	0.98
		10 mg	1/794	4/1928	0.69 (0.11-4.38)	0	0.70
		15 mg	1/803	4/1928	1.03 (0.13-8.06)	24	0.98
	GLP-1RA	Pooled	9/2045	1/682	1.08 (0.12-9.72)	37	0.94
		5 mg	2/684	1/682	1.35 (0.10-18.81)	31	0.82
		10 mg	3/678	1/682	1.81 (0.30-11.07)	0	0.52
		15 mg	4/683	1/682	1.87 (0.07-48.28)	56	0.71
Nephrolithiasis	Placebo	Pooled	5/3666	3/1533	0.75 (0.21-2.70)	0	0.65
		5 mg	2/914	0/926	2.96 (0.31-28.07)	0	0.35
		10 mg	1/1235	0/1241	3.03 (0.12-74.06)	NA	0.50
		15 mg	2/1517	3/1533	1.01 (0.13-7.74)	22	0.99
	Insulin	Pooled	4/2072	1/1360	1.49 (0.20–11.28)	0	0.70
		5 mg	2/687	1/1360	3.03 (0.37-24.57)	0	0.30
		10 mg	1/688	1/1360	1.74 (0.18-16.74)	0	0.63
		15 mg	1/697	1/1360	1.72 (0.18-16.51)	0	0.64
	GLP-1RA	Pooled	4/1886	0/628	1.67 (0.20-14.26)	0	0.64
		5 mg	1/629	0/628	2.99 (0.12-73.30)	NA	0.50
		10 mg	1/627	0/628	3.00 (0.12-73.45)	NA	0.50
		15 mg	2/630	0/628	4.97 (0.2-102.69)	0	0.64
Acute kidney injury	Placebo	Pooled	8/2965	2/1301	1.39 (0.38-5.11)	0	0.62
		5 mg	2/685	1/694	2.04 (0.19–22.45)	NA	0.56
		10 mg	5/999	2/1009	2.16 (0.47-10.00)	0	0.32
		15 mg	1/1281	2/1301	0.71 (0.11-4.47)	0	0.71
	Insulin	Pooled	5/2789	4/2068	0.91 (0.17-4.95)	30	0.91
		5 mg	2/930	4/2068	1.32 (0.28–6.28)	0	0.73
		10 mg	2/926	4/2068	1.33 (0.25-7.00)	6	0.74
		15 mg	1/933	4/2068	1.04 (0.13-8.05)	23	0.97
	GLP-1RA	Pooled	2/1568	0/523	1.02 (0.11-9.71)	0	0.99
		5 mg	0/525	0/523	Not estimable	NA	NA
		10 mg	1/520	0/523	3.17 (0.13-76.16)	NA	0.48
		15 mg	1/523	0/523	2.99 (0.12-73.30)	NA	0.50
Renal cancer	Placebo	Pooled	2/2538	1/1055	0.71 (0.11-4.72)	5	0.72
		5 mg	1/746	1/763	1.03 (0.11-9.86)	0	0.98
		10 mg	0/755	1/763	0.34 (0.01-8.26)	NA	0.51
		15 mg	1/1037	1/1055	1.02 (0.11-9.78)	0	0.99
	Insulin	Pooled	2/1702	0/1708	3.00 (0.31-28.85)	0	0.34
		5 mg	1/562	0/1708	9.38 (0.38-229.79)	NA	0.17
		10 mg	0/566	0/1708	Not estimable	NA	NA
		15 mg	1/574	0/1708	8.97 (0.37-219.56)	NA	0.18
	GLP-1RA	Pooled	2/1886	0/628	1.00 (0.10-9.61)	0	1.00
		5 mg	1/629	0/628	3.00 (0.12-73.09)	NA	0.50
		10 mg	1/627	0/628	3.00 (0.12-73.45)	NA	0.50
		15 mg	0/630	0/628	Not estimable	NA	NA

CI: Confidence interval; GLP-1RA: Glucagon-like peptide-1 receptor agonists; NA: Not applicable; RR: Risk ratio; UTI: Urinary tract infection.