Reasons for discontinuing tirzepatide in randomized controlled trials: A systematic review and meta-analysis

Table 1 Summary of the results of meta-analyses of the reasons for study drug discontinuation, n of participants with outcome/n of participants analyzed

Outcome variables	Control group	Tirzepatide dose	Tirzepatide arm	Control arm	Pooled effect size, RR [95%CI]	I2, %	P value
Failure to meet randomization criteria	Placebo	15 mg	8/355	16/350	0.50 [0.22-1.15]	0	0.10
	Insulin	5 mg	1/687	1/1365	1.75 [0.07-44.70]	51	0.73
		10 mg	1/690	1/1365	1.74 [0.07-44.62]	51	0.74
		15 mg	0/697	1/1365	0.33 [0.01-8.18]	NA	0.50
Protocol deviation	Placebo	5 mg	0/801	4/814	0.28 [0.05-1.69]	0	0.16
		10 mg	3/1217	8/1224	0.55 [0.17-1.85]	0	0.33
		15 mg	5/1764	9/1751	0.63 [0.22-1.84]	0	0.40
	Insulin	5 mg	1/687	3/1365	1.06 [0.12-9.34]	0	0.96
		10 mg	1/690	3/1365	1.02 [0.11-9.73]	NA	0.99
		15 mg	2/697	3/1365	1.43 [0.23-9.08]	0	0.70
	GLP-1RA	5 mg	1/685	3/682	0.43 [0.06-2.93]	0	0.39
		10 mg	2/678	3/682	0.84 [0.15-4.67]	0	0.84
		15 mg	1/683	3/682	0.43 [0.06-2.92]	0	0.39
Adverse events	Placebo	5 mg	38/853	24/857	1.58 [0.95-2.62]	0	0.08
		10 mg	69/1266	38/1267	1.74 [1.12-2.71]	7	0.01
		15 mg	133/1841	54/1839	2.38 [1.55-3.66]	30	< 0.001
	Insulin	5 mg	68/1160	34/2306	3.87 [2.54-5.89]	0	< 0.00001
		10 mg	101/1156	34/2306	5.20 [3.47-7.79]	0	< 0.00001
		15 mg	118/1162	34/2306	6.37 [4.31-9.41]	0	< 0.00001
	GLP-1RA	5 mg	41/685	33/682	1.23 [0.79-1.92]	0	0.36
		10 mg	55/678	33/682	1.55 [0.85-2.83]	39	0.16
		15 mg	69/711	33/726	2.07 [1.39-3.08]	0	0.0003
Non-adherence with study treatment	Placebo	15 mg	2/292	2/261	0.68 [0.06-7.42]	20	0.76
Lost to follow up	Placebo	5 mg	19/848	42/862	0.52 [0.25-1.10]	17	0.09
		10 mg	20/1165	49/1177	0.42 [0.25-0.70]	0	0.0008
		15 mg	32/1711	68/1749	0.74 [0.31-1.74]	57	0.49
	Insulin	5 mg	12/930	21/2076	1.22 [0.58-2.59]	0	0.60
		10 mg	9/928	21/2076	0.93 [0.40-2.18]	0	0.87
		15 mg	8/933	21/2076	0.84 [0.37 -1.93]	0	0.69
	GLP-1RA	5 mg	4/685	10/ 682	0.43 [0.14-1.28]	0	0.13
		10 mg	5/678	10/682	0.53 [0.19-1.50]	0	0.23
		15 mg	11/711	10/726	1.06 [0.46-2.46]	0	0.88
Withdrawal by subject	Placebo	5 mg	42/848	93/862	0.83 [0.20-3.34]	61	0.79
		10 mg	50/1264	121/1272	0.45 [0.29-0.70]	15	0.0004
		15 mg	74/1840	202/1844	0.39 [0.26-0.59]	35	< 0.00001
	Insulin	5 mg	24/1160	135/2306	0.35 [0.22-0.54]	0	< 0.00001
		10 mg	33/1156	135/2306	0.42 [0.24-0.76]	45	0.004
		15 mg	31/1162	135/2306	0.46 [0.31-0.69]	0	0.0001
	GLP-1RA	5 mg	10/685	10/682	0.97 [0.39-2.39]	0	0.94
		10 mg	12/678	10/682	1.20 [0.52-2.79]	0	0.66
		15 mg	16/711	11/726	1.44 [0.66-3.16]	0	0.36
Physician decision	Placebo	5 mg	2/677	3/691	0.75 [0.14-3.99]	0	0.74
		10 mg	4/1094	5/1101	0.87 [0.27-2.85]	0	0.82
		15 mg	9/1639	10/1628	0.83 [0.34-2.04]	0	0.69
	Insulin	5 mg	1/1160	22/2306	0.23 [0.05-1.00]	0	0.05
		10 mg	7/1156	22/2306	0.80 [0.33-1.91]	0	0.61
		15 mg	8/1162	22/2306	0.85 [0.24-3.00]	30	0.80
	GLP-1RA	5 mg	0/630	2/628	0.20 [0.01-4.14]	NA	0.30
		10 mg	7/627	2/628	2.51 [0.51-12.35]	6	0.26
		15 mg	1/630	2/628	0.74 [0.05-10.39]	31	0.82
Pregnancy	Placebo	10 mg	8/1018	6/1027	1.36 [0.47-3.88]	0	0.57
		15 mg	9/1533	8/1554	1.15 [0.45-2.96]	0	0.77
Death	Insulin	5 mg	15/1160	48/2306	0.96 [0.54-1.69]	0	0.88
		10 mg	5/1056	48/2306	0.37 [0.09-1.48]	37	0.16
		15 mg	7/1162	48/2306	0.44 [0.20-0.95]	0	0.04
Other	Placebo	5 mg	5/801	20/814	0.28 [0.11-0.71]	0	0.007
		10 mg	7/1217	26/1224	0.30 [0.14-0.67]	0	0.003
		15 mg	19/1764	43/1751	0.45 [0.26-0.78]	0	0.004
	Insulin	5 mg	7/1160	18/2306	0.87 [0.34-2.18]	0	0.76
		10 mg	7/1156	18/2306	1.08 [0.46-2.55]	0	0.86
		15 mg	6/1162	18/2306	0.83 [0.34-2.04]	0	0.69
	GLP-1RA	5 mg	1/685	2/682	0.69 [0.11-4.33]	0	0.69
		10 mg	3/678	2/682	1.39 [0.19-10.42]	14	0.75
		15 mg	5/683	2/682	1.70 [0.13-22.46]	47	0.69

RR: Risk ratio; CI: Confidence interval; GLP-1RA: Glucagon-like peptide-1 receptor agonists; NA: Not available.