Table 4.

Studies regarding the impact of adherence or persistence on healthcare costs (n = 14)

Author	Medication and study population	Adherence/persistence	Costs for adherent/persistent vs nonadherent/nonpersistent groups
Buysman [34]	GLP-1 RA, naïve, initiators on oral medications and/or insulin	Adherence and persistence: 1 year	Diabetes-related, unadjusted (mean [SD]; median)  Total: $9,081 ($8685); $6797 vs $7717 ($13,679); $4647, P = 0.028  Pharmacy total: $6338 ($2,639); $5606 vs $3568 ($2439); $3074, P < 0.001  Total medical: $2743 ($8,065); $683 vs $4149 ($13,383); $687, P = 0.018
		Adherence: 1 year	Diabetes-related, adjusted  Total (95%CI): $9419 ($8574-10,308) vs $7667 ($6903-8573), P = 0.005  Pharmacy total (estimated from figure): $6000 vs $4000, P < 0.001  Total medical (estimated from figure): $3000 vs $4000, P = 0.080
		Persistence: 1 year	Diabetes-related, unadjusted (mean [SD]; median)  Total: $8675 ($10,611); $6180 vs $7447 ($14,270); $3864, P = 0.092  Pharmacy total: $5571 ($2658); $5039 vs $2931 ($2298); $2341, P < 0.001  Total medical: $3103 ($10,124); $682 vs $4516 ($14,017); $699, P = 0.047
		Persistence: 1 year	Diabetes-related, adjusted (mean)  Total (estimated from figure): $8700 vs $7500, P = 0.010  Pharmacy total (estimated from figure): $5000 vs $3500, P = 0.010  Total medical (stated in text): $3298 vs $4805, P = 0.017
Lin [31]	aInitiators of combination of GLP-1 RA and insulin	Persistence: 1 year	All-cause, unadjusted  Total: $43,096 vs $51,084, P = 0.028  Pharmacy total: $14,691 vs $10,791, P < 0.001  Total medical: $28,405 vs $40,292, P = 0.001
		Persistence: 1 year	Diabetes-related, unadjusted  Total: $19,255 vs $20,327, P = 0.441  Pharmacy total: $8142 vs $5124, P < 0.001  Total medical: $11,114 vs $15,203, P = 0.003
Kalirai [30]	Insulin, naïve, initiators	Persistence: 1 and 2 years	Year 1: Adjusted estimates from regression models  All-cause total medical, inpatient and ED costs were significantly lower, but not outpatient costs  Diabetes related total medical, inpatient and ED costs were significantly lower, but not outpatient costs  Diabetes-related pharmacy basal and other insulins and total pharmacy costs were significantly higher, but this was not true for other injectables and oral antidiabetic medications  All-cause healthcare (medical + pharmacy) costs were nonsignificantly lower for continuers Year 2: Results were similar with the exception that diabetes-related pharmacy costs for injectables were also significantly higher for continuers
Ascher-Svanum [8]	Insulin, naïve, initiators	Early discontinuation (gap ≥ 30 days after first prescription): 1 year	Adjusted estimates from regression models, all P values < 0.05  Acute care costs (inpatient + ED): 9.6% higher  Outpatient costs: 6.4% lower  Diabetes-related pharmacy costs: 42.9% lower  All-cause pharmacy costs: 34.0% lower Total medical costs: 10.9% lower
Wu [17]	Insulin, non-naïve, upon discharge from hospital	Persistence: 6 months	Regression models with adjustment for pre-discharge costs and other baseline covariates  Lower total medical service costs (difference of $2569, P = 0.007)  Results driven by lower facility and other services costs (difference of $2265; P = 0.010), and physician service costs (difference of $524; P = 0.001) (pharmacy costs not reported)
Perez-Nieves [29]	Insulin, naive, initiators of non-mixed basal insulin during study period	Continuers vs interrupters vs discontinuers	Year 1  Continuers had lower medical costs (continuers: $10,890, interrupters: $13,674, discontinuers $13,021  Continuers had higher pharmacy costs (continuers: $7449, interrupters: $5239, discontinuers $4857   P < 0.05 for all comparisons of continuers vs interrupters and continuers vs discontinuers  Total healthcare costs similar across the 3 cohorts Year 2: findings were similar
Anderten [14]	Insulin, naive, initiators of basal insulin	Persistence: 1 year	No differences in treatment or prescription costs or medical services by persistence to insulin glargine vs NPH
Kleinman [27]	Insulin, naive, initiators	Adherence (MPR): 1 year	Regression models stratified by high vs low prior costs  Higher MPR was associated with significantly lower total healthcare costs for patients with high (upper quartile) prior costs: $450 in savings per 10% increase in MPR  Higher MPR was associated with significantly higher total healthcare costs for patients with low (lower quartile) prior costs (amount not stated)  Both groups of patients experienced significantly lower medical costs (removing prescription costs) when MPR was high   Higher prior cost group: 100% MPR group had $6,653 in medical costs vs 10% MPR group had $11,763 in medical costs   Lower prior cost group: 100% MPR group had $3329 in medical costs vs 10% MPR group had $4,590 in medical costs
Ayyagari [15]	Insulin, naïve, previously on oral medication or GLP-1 RA	Adherence: 1 year	Adjusted costs using marginal structural models  Pharmacy costs higher for adherent insulin users, averaging an additional $2,074 more annually for pen users and $2923 more for vial users (P < 0.001 for both patterns)  Annual health care costs for both pen and vial users demonstrated lower costs for nonadherent patients, but these differences were not statistically significant
Cobden [26]	Insulin, continuing, who converted from an insulin analog or human insulin administered using a vial/syringe to a biphasic insulin analog administered with a pen device	Adherence (MPR ≥ 80%): 2 years	Adjusted costs  Adherence was associated with significant reductions in all-cause healthcare costs (exponentiated coefficient estimate 0.55, 95% CI 0.31–0.80, P < 0.05). This implies an average 45% decrease in all-cause total healthcare costs for adherent compared to nonadherent patients
Wei [5]	Insulin, naïve, receiving > 1 oral medication or GLP-1 RA	Persistence: 1 year	Unadjusted costs  Pharmacy costs: $5761 vs $4319, P < 0.0001  Total medical costs: $17,007 vs $18,367, P = 0.1419
Hadjiyianni [25]	Insulin, naive, initiators of basal insulin	Continuers vs interrupters vs discontinuers:1 year	Adjusted costs (in yen)  Those who interrupted or discontinued had higher costs of hospitalization than continuers  Total costs did not differ among the 3 groups  Total medical costs did not differ among the 3 groups  Total pharmacy costs were higher for the continuers
Chandran [28]	Insulin, naive, pen prescription within study period	Adherence (MPR): 1 year	Unadjusted costs  Average annual per-patient healthcare expenditures (P = 0.007)   Least adherent group (MPR < 0.20, 11.0% of patients): $26,310   Most adherent group (MPR > 0.80; 34.6% of patients): $23,839  Average annual per-patient pharmacy expenditures (P < 0.001)   Least adherent group: $5395   Most adherent group: $10,174
Perez-Nieves [9]	Insulin, naïve, initiating basal insulin	Continuers vs interrupters vs discontinuers (identified retrospectively)	Cross-sectional survey  The three groups did not differ in reporting the impact of insulin use on budget management

^aText of article is unclear regarding whether the numbers reported are charges or costs of care

GLP-1 RA glucose-like peptide-1 receptor agonist, SD standard deviation, ED emergency department, MPR medication possession ratio, CI confidence interval