. 2022 Oct 10;13:882998. doi: 10.3389/fendo.2022.882998

Table 3.

Hazard Ratios for MOF in subgroup and sensitivity analyses.

Analysis	n =	Fractures, n (%)	Unadjusted (HR [95% CI])	Age & sex (HR [95% CI])	Full model (HR [95% CI])
Males	GLP-1 RA: 9,409	103 (1.1)	0.90 [0.68 – 1.18]	0.90 [0.69 – 1.18]	0.85 [0.64 – 1.12]
Males	DPP-4i: 9,409	101 (1.1)	0.90 [0.68 – 1.18]	0.90 [0.69 – 1.18]	0.85 [0.64 – 1.12]
Females	GLP-1 RA: 6,622	184 (2.8)	0.96 [0.78 – 1.19]	1.00 [0.80 – 1.23]	0.97 [0.77 – 1.22]
Females	DPP-4i: 6,622	156 (2.4)	0.96 [0.78 – 1.19]	1.00 [0.80 – 1.23]	0.97 [0.77 – 1.22]
MPR ≥ 0.5	GLP-1 RA: 12,897	222 (1.7)	0.90 [0.75 – 1.09]	0.92 [0.76 – 1.11]	0.87 [0.71 – 1.06]
MPR ≥ 0.5	DPP-4i: 12,897	211 (1.6)	0.90 [0.75 – 1.09]	0.92 [0.76 – 1.11]	0.87 [0.71 – 1.06]
MPR ≥ 0.75	GLP-1 RA: 9,590	152 (1.6)	0.80 [0.64–0.998]	0.81 [0.64 – 1.01]	0.75 [0.60 – 0.95]
MPR ≥ 0.75	DPP-4i: 9,590	163 (1.7)	0.80 [0.64–0.998]	0.81 [0.64 – 1.01]	0.75 [0.60 – 0.95]
MPR ≥ 0.95	GLP-1 RA: 6,195	83 (1.3)	0.72 [0.54 – 0.97]	0.73 [0.54 – 0.96]	0.62 [0.46 – 0.84]
MPR ≥ 0.95	DPP-4i: 6,195	99 (1.6)	0.72 [0.54 – 0.97]	0.73 [0.54 – 0.96]	0.62 [0.46 – 0.84]
No CKD etc.	GLP-1 RA: 14,726	251 (1.7)	0.88 [0.74 – 1.05]	0.90 [0.75 – 1.07]	0.85 [0.70 – 1.02]
No CKD etc.	DPP-4i: 14,726	244 (1.7)	0.88 [0.74 – 1.05]	0.90 [0.75 – 1.07]	0.85 [0.70 – 1.02]
6+ months follow-up	GLP-1 RA: 12,695	275 (2.2)	0.86 [0.73 – 1.02]	0.88 [0.74 – 1.04]	0.84 [0.71 – 1.00]
6+ months follow-up	DPP-4i: 12,695	274 (2.2)	0.86 [0.73 – 1.02]	0.88 [0.74 – 1.04]	0.84 [0.71 – 1.00]
Liraglutide	GLP-1 RA: 14,961	280 (1.9)	0.92 [0.77 – 1.09]	0.93 [0.79 – 1.11]	0.89 [0.75 – 1.06]
Liraglutide	DPP-4i: 14,961	249 (1.7)	0.92 [0.77 – 1.09]	0.93 [0.79 – 1.11]	0.89 [0.75 – 1.06]
Semaglutide	GLP-1 RA: 615	1 (0.2)	0.81 [0.11 – 5.98]	N/A	N/A
Semaglutide	DPP-4i: 4,305	71 (1.6)	0.81 [0.11 – 5.98]	N/A	N/A
Exenatide	GLP-1 RA: 435	3 (0.7)	0.42 [0.13 – 1.34]	N/A	N/A
Exenatide	DPP-4i: 3,480	52 (1.5)	0.42 [0.13 – 1.34]	N/A	N/A
Dulaglutide	GLP-1 RA: 325	3 (0.9)	1.25 [0.32 – 4.91]	N/A	N/A
Dulaglutide	DPP-4i: 975	13 (1.3)	1.25 [0.32 – 4.91]	N/A	N/A
Lixisenatide	GLP-1 RA: 15	0 (0)	N/A	N/A	N/A
Lixisenatide	DPP-4i: 150	2 (1.3)	N/A	N/A	N/A
Full cohort (unmatched)	GLP-1 RA: 16,723	290 (1.7)	0.67 [0.58 – 0.78]	0.91 [0.78 – 1.05]	0.87 [0.74 – 1.02]
Full cohort (unmatched)	DPP-4i: 26,093	578 (2.2)	0.67 [0.58 – 0.78]	0.91 [0.78 – 1.05]	0.87 [0.74 – 1.02]
Glucocorticoid as exclusion	GLP-1 RA: 14,635	242 (1.7)	0.93 [0.78 – 1.12]	0.95 [0.79 – 1.14]	0.89 [0.74 – 1.08]
Glucocorticoid as exclusion	DPP-4i: 14,635	219 (1.5)	0.93 [0.78 – 1.12]	0.95 [0.79 – 1.14]	0.89 [0.74 – 1.08]
Intention-to-treat analysis	GLP-1 RA: 16,133	410 (2.5)	0.89 [0.78 – 1.02]	0.90 [0.79 – 1.03]	0.85 [0.74 – 0.98]
Intention-to-treat analysis	DPP-4i: 16,133	425 (2.6)	0.89 [0.78 – 1.02]	0.90 [0.79 – 1.03]	0.85 [0.74 – 0.98]

DPP-4i, dipeptidyl peptidase 4 inhibitor; GLP-1 RA, glucagon-like peptide-1 receptor agonists; HR, Hazard Ratio; MOF, major osteoporotic fracture; MPR, medication possession rate; N/A, not available. Bold font = the HR was significantly different from 1.00.

“No pause”: excluded those with pauses in metformin, SGLT2 inhibitor or GLP-1 receptor agonist during the study period. “No CKD etc.”: Excluded those with chronic kidney disease, previous falls and previous chronic pancreatitis. “6+ months follow-up”: Excluding all with follow-up times less than 183 days.

Full model: Adjusted for sex, age, inclusion date, diabetes duration, Charlson Comorbidity Index, any diabetic complications, previous falls, inflammatory bowel disease, ever insulin use, ever glucocorticoid use, hypertension, kidney disease, alcohol, smoking and obesity, and stratified by osteoporosis.