Patient preferences for glucagon-like peptide 1 receptor–agonist treatment attributes

Figures & data

Figure 1 Flow diagram of study selection.

Notes: ^aOne congress abstract identified in the main bibliographic database search and one from the hand-search. ^bStudy sponsors: Lilly, n=5; Novo Nordisk, n=2; AstraZeneca, n=2; AstraZeneca/Bristol-Myers Squibb, n=1.
Abbreviations: CENTRAL, Cochrane Controlled Register of Trials; HTA, Health Technology Assessment; NHS EED, National Health Service Economic Evaluation Database.

Table 1 Summary of studies comparing different GLP1 RAs included in the review

	Country	n	Population characteristics	Participant recruitment	Preference evaluation	Survey administration	Comparators
Gelhorn et al^Citation18	UK	243	T2DM, injection-naïve, mean age 60.5±10.9 years, 76.1% male	Newspaper/internet/classified advertisements	DCE	Administration by trained moderator of patient self-completed questionnaires	Dulaglutide QW Liraglutide QD
Gelhorn et al^Citation19	Japan	182	T2DM, injection-naïve, mean age 58.9±10.0 years, 64.3% male	Advertisement on closed online clinical volunteer database	DCE	Administration by trained moderator of patient self-completed questionnaires	Dulaglutide QW Liraglutide QD
Hauber et al^Citation20	USA	643	T2DM, injection-experienced and injection-naïve, mean age 52.7±15.0 years, 57.1% male	Existing T2DM ailment panel	DCE	Online self-administered survey	Liraglutide QD Exenatide QW
Jendle et al^Citation24	Sweden	461	T2DM, age/sex NR	Existing email panel	WTP	Online self-administered survey	Liraglutide QD Exenatide BID
Matza et al^Citation12	UK	209	T2DM, injection-experienced and injection-naïve, mean age 60.4±8.9 years, 57.4% male	Newspaper/online advertisements, fliers near interview sites, patient advocacy group newsletters	TTO	One-to-one interviews	QW GLP1 RA injections
Matza et al^Citation21	Italy	238	T2DM, injection-experienced and injection-naïve, mean age 60.2±9.3 years, 58.8% male	Database of previous study volunteers	TTO	One-to-one interviews	QW GLP1 RA injections
Polster et al^Citation22	USA	382	T2DM, injection-experienced and injection-naïve, mean age 53.0±8.75 years, 48.0% male	Online web panel	TTO DCE	Online self-administered survey	Liraglutide QD Exenatide BID
Qin et al^Citation15	Brazil, China, Germany, Japan, UK	1,482	T2DM, injection-naïve, mean age 56.0±11.4 years, 68.0% male	Patient databases, referrals from clinicians and patient associations, targeted publication advertisements	DCE	Online self-administered survey	Liraglutide QD Exenatide QW
Qin et al^Citation23	Germany, UK	510	T2DM, injection-experienced, mean age 57.0±11.0 years, 51.4% male	Patient databases, referrals from clinicians and patient associations, targeted publication advertisements	DCE	Online self-administered survey	Liraglutide QD Exenatide QW

Abbreviations: BID, bis in die (twice daily); DCE, discrete-choice experiment; NR, not reported; QD, quaque die (once daily); QW, once weekly; RAs, receptor agonists; T2DM, type 2 diabetes mellitus; TTO, time trade-off; WTP, willingness to pay.

Table 2 Summary of studies comparing GLP1 RAs and insulin glargine included in the review

	Country	n	Population characteristics	Participant recruitment	Preference evaluation	Survey administration	Comparators
Jendle et al^Citation24	Sweden	461	T2DM, age/sex NR	Existing email panel	WTP	Online self-administered survey	Liraglutide QD Insulin glargine
Poon et al^Citation17	UK	232	T2DM, injectable-naïve, mean age 61.8±10.8 years, 74.1% male	Newspaper/magazine advertisement	DCE	Administration by trained moderator of patient self-completed questionnaires	Dulaglutide QW Insulin glargine (Lantus SoloStar)

Abbreviations: DCE, discrete-choice experiment; NR, not reported; QD, quaque die (once daily); QW, once weekly; RAs, receptor agonists; T2DM, type 2 diabetes mellitus; WTP, willingness to pay.

Figure 2 Frequency of individual treatment-attribute evaluation across ten patient-preference studies identified by literature review.

Notes: ^aVariously across studies: MUP, SUP, vial and syringe, or autoinjector. ^bInjection preparation associated with vial and syringe, SUP, MUP, and autoinjector (Qin et al).^{15,23 c}In one study, nausea was described as “frequency of GI AEs,” but described by levels of nausea incidence only (Poon et al).^{17 d}Common AEs are a combination of nausea, vomiting, diarrhea, and injection-site nodules (Qin et al).^15,23
Abbreviations: AE, adverse event; BG, blood glucose; GI, gastrointestinal; HbA_lc, glycated hemoglobin; MUP, multiuse pen; SBP, systolic blood pressure; SUP, single-use pen.

Table 3 Key results from DCEs evaluating preference for profiles of different GLP1 RAs in patients with T2DM

	Injection experience	Key results
Gelhorn et al^Citation18	Injection-naïve	Most important attributes: dose frequency (RI 41.6%) and type of delivery system (35.5%); others of minor importance (frequency of nausea 10.4%, weight change 5.9%, HbAlc change 3.6%, frequency of hypoglycemia 3.0%)
Gelhorn et al^Citation19	Injection-naïve	Most important attributes: dose frequency (RI 44.1%) and type of delivery system (26.3%); others of minor importance (frequency of nausea 15.1%, frequency of hypoglycemia 7.4%, weight change 6.2%, HbAlc change 1.0%)
Hauber et al^Citation20	Injection-experienced and -naïve	Better device attributes preferred to worse attributes in all groupsa Change from QW to QD most important attribute in all groups; switching from longer/thicker to shorter/thinner needle and elimination of injection-site nodules also important predictors of choice All process attributes less important to patients when dosing was less frequent (ie, QW versus QD)
Jendle et al^Citation24	NR	WTP for liraglutide (1.2 mg/day) versus exenatide (20 μg): change in HbAlc at 26 weeks €0.27/day, change in SBP at 26 weeks €0.20/day, change in body weight at 26 weeks −€0.46/day, minor hypoglycemia event rate €0.07/day, administration (frequency and mealtime dosing) €1.04/day, BG tests €0.00/day, frequency of nausea €0.08/day Overall, patients were prepared to pay an extra €0.81/day for liraglutide QD compared with exenatide BID
Polster et al^Citation22	Injection-experienced and -naïve	HbAlc change and frequency of nausea most important attributes (RI 39% and 30%, respectively); frequency of hypoglycemia and dose schedule less important (17% and 14%, respectively)b
Qin et al^Citation15	Injection-naïve	AEs, HbAlc change, and dose frequency most important attributes (ORs 2.14, 1.85, and 1.63, respectively; all P<0.05); less important were evidence of long-term efficacy/safety, need for titration, required preparation, type of device, and needle size (ORs 1.30, 1.12, 1.09, 1.04, and 1.03, respectively; all P<0.05) 64.2%, 31.1%, and 4.7% stated that QW, QD, and BID injectable regimens were easiest to follow
Qin et al^Citation23	Injection-experienced	AEs, HbAlc change, dose frequency, required preparation, and evidence of long-term efficacy/safety were most important attributes (ORs 2.67, 2.58, 2.26; 1.71, and 1.13, respectively; all P≤0.01); type of device, needle size, and need for titration not significant predictors of preference HbAlc change (1.5-point improvement) was the most valued attribute in German patients (Germany versus UK OR 3.27 versus 2.00), while AE profile most valued in UK patients (Germany versus UK OR 2.91 versus 2.50) 72.0%, 27.1%, and 1.0% stated that QW, QD, and BID injectable regimens were easiest to follow

Notes:

a With exception of need for storage in a refrigerator, which was unexpectedly preferred by current liraglutide QD and insulin users;

b dose schedule included frequency and timing (QD without regard to mealtimes versus QW during the hour prior to main meal).

Abbreviations: AE, adverse event; BG, blood glucose; BID, bis in die (twice daily); DCEs, discrete-choice experiments; HbA_lc, glycated hemoglobin; NR, not reported; QD, quaque die (once daily); QW, once weekly; RAs, receptor agonists; RI, relative importance; SBP, systolic blood pressure; T2DM, type 2 diabetes mellitus; WTP, willingness to pay.

Table 4 Importance of attributes of GLP1 RA treatments determined in DCEs conducted in patients with T2DM

	Attribute importance
	1 (most important)	2	3	4	5	6	7	8 (least important)
Gelhorn et al^Citation18 (injectable-naïve)	Dose frequency	Type of device	Nausea	Weight change	Change in HbAlc	Hypoglycemia
Gelhorn et al^Citation19 (injectable-naïve)	Dose frequency	Type of device	Nausea	Hypoglycemia	Weight change	Change in HbAlc
Hauber et al^20,a
Exenatide QW users	Dose frequency	Injection-site reactions	Needle size	Type of device	Storage
Liraglutide QD users	Dose frequency	Type of device	Needle size	Injection-site reaction	Storage
Insulin-only users	Dose frequency	Needle size	Type of device	Injection-site reaction	Storage
Injectable-naïve	Dose frequency	Needle size	Storage	Injection-site reaction	Type of device
Polster et al^Citation22 (injectable-experienced and -naïve)	Change in HbAlc	Nausea	Hypoglycemia	Dose frequency
Qin et al^Citation15 (injectable-naïve)	AE profile	Change in HbAlc	Dose frequency	Long-term efficacy/safety	Titration	Injection preparation	Type of device	Needle size
Qin et al^Citation23 (injectable-experienced)	AE profile	Change in HbAlc	Dose frequency	Injection preparation	Long-term efficacy/safety	Type of device	Needle size	Titration

Notes: For type of device, levels evaluated included SUP and MUP (Gelhorn et al);^18,19 SUP, MUP, and vial and syringe (Hauber et al);²⁰ and SUP, MUP, vial and syringe, and autoinjector (Qin et al).^15,23

a Importance rankings for QD dosing. Attributes were less important when dosing was QW, although ranking remained the same. Efficacy held constant in all DCE pairs.

Abbreviations: AE, adverse event; DCEs, discrete-choice experiments; HbA_lc, glycated hemoglobin; MUP, multiuse pen; QD, quaque die (once daily); QW, once weekly; SUP, single-use pen; RAs, receptor agonists; T2DM, type 2 diabetes mellitus.

Figure 3 Preference for hypothetical GLP1 RA drug profiles determined in DCEs among patients with T2DM. (A) Preferences for a dulaglutide QW versus liraglutide QD profile among injectable-naive patients; (B) preferences for a exenatide QW versus liraglutide QD profile among injectable-naive or injectable-experienced patients; (C) preferences for a exenatide BID versus liraglutide QD profile in injectable and naive patients.

Notes: In Qin et al (B),^15,23 patients were asked to assume that hypothetical profiles had equal efficacy. Even when liraglutide QD was assumed to have superior efficacy to exenatide QW, the exenatide profile was preferred (70.4% versus 29.6% in injection-naïve and 68.2% versus 31.8% in injection-experienced). In Hauber et al (B),²⁰ efficacy of hypothetical profiles was held to be equal. There was an even split in preference for exenatide QW vial and syringe versus SUP in exenatide QW users (34.2% versus 35.4%), but injection-naïve patients preferred the SUP over vial and syringe (46.3% versus 39.4%). ^†P<0.001; ^‡P<0.0001.
Abbreviations: BID, bis in die (twice daily); DCEs, discrete-choice experiments; QD, quaque die (once daily); QW, once weekly; RA, receptor agonist; SUP, single-use pen; T2DM, type 2 diabetes mellitus.

Table 5 Health-utility scores for health states described by different attributes of injection-delivery systems for weekly GLP1 RA therapies in patients with T2DM in UK and Italian TTO evaluations

	Mean utility (SD)a		Mean disutility (SD)
			Difference from health state A		Difference from health state G
	UK (Matza et al)^Citation12	Italy (Matza et al)^Citation21	UK (Matza et al)^Citation12	Italy (Matza et al)^Citation21	UK (Matza et al)^Citation12	Italy (Matza et al)^Citation21
A: Oral treatment only	0.888 (0.120)	0.900 (0.097)	–	–	–	–
Health states with oral and injectable treatment
B: Reconstitution, waiting, needle handling	0.858 (0.165)	0.868 (0.109)	−0.030 (0.073)	−0.032 (0.059)	−0.020 (0.042)	−0.022 (0.052)
C: Reconstitution, waiting	0.863 (0.161)	0.872 (0.109)	−0.025 (0.066)	−0.027 (0.058)	−0.014 (0.032)	−0.018 (0.052)
D: Reconstitution, needle handling	0.868 (0.159)	0.879 (0.102)	−0.020 (0.063)	−0.020 (0.040)	−0.010 (0.027)	−0.011 (0.030)
E: Reconstitution	0.874 (0.157)	0.884 (0.100)	−0.014 (0.058)	−0.015 (0.032)	−0.004 (0.016)	−0.006 (0.021)
F: Needle handling	0.874 (0.156)	0.884 (0.101)	−0.014 (0.058)	−0.016 (0.033)	−0.004 (0.015)	−0.006 (0.021)
G: No inconveniences	0.878 (0.156)	0.890 (0.100)	−0.010 (0.056)	−0.009 (0.025)	–	–

Notes:

a TTO scores on a scale anchored by 0 = dead and 1 = full health.

Abbreviations: RA, receptor agonist; T2DM, type 2 diabetes mellitus; TTO, time trade-off.

Table 6 Overview of key results from studies that compared preferences for treatment attributes of GLP1 RAs with insulin glargine

	Injection experience	Key results
DCE with WTP
Jendle et al^Citation24	NR	WTP for liraglutide (1.2 mg/day) versus insulin glargine: change in HbAlc at 26 weeks €0.04/day, change in SBP at 26 weeks €0.65/day, change in body weight at 26 weeks €2.35/day, minor hypoglycemia-event rate €0.03/day, administration (frequency and mealtime dosing) €0.00/day, BG tests €0.33/day, frequency of nausea −€0.04/day Overall, patients prepared to pay an extra €3.36/day for liraglutide QD compared with insulin glargine
DCE
Poon et al^Citation17	Injection-naïve	RI of attributes in rank order: 1) type of delivery system (RI 19.8%); 2) frequency of GI AEs (18.2%); 3) dosing frequency (17.7%); 4) weight change (15.6%); 5) HbAlc change (14.2%); 6) frequency of pancreatitis (12.3%); 7) frequency of hypoglycemia (2.2%) Patients preferred a medication profile administered by SUP, with fewer AEs, weight loss, and greater HbAlc change

Abbreviations: AEs, adverse events; BG, blood glucose; DCE, discrete-choice experiment; GI, gastrointestinal; HbA_lc, glycated hemoglobin; NR, not reported; QD, quaque die (once daily); QW, once weekly; RAs, receptor agonists; RI, relative importance; SBP, systolic blood pressure; SUP, single-use pen; WTP, willingness to pay.

Table

1 Glucagon-Like Peptide-1 Receptor/(2091)

2 Glucagon-Like Peptide 1/(6642)

3 Glucagon-Like Peptides/(1313)

4 Receptors, Glucagon/(2281)

5 ((glucagon-like peptide-1 or glucagon-like peptide1 or glp-1 or glp1) adj5 (agonist$1 or analogue$1 or stimulating agent$1)).ti,ab,kf,rn,nm. (3626)

6 ((glucagon-like peptide-1r or glucagon-like peptide1r or glp-1r or glp1r) adj5 (agonist$1 or analogue$1 or stimulating agent$1)). ti,ab,kf,rn,nm. (426)

7 (glp-1-ra or glp1-ra or glp-1ra or glp1ra or glp-1-ras or glp1-ras or glp-1ras or glp1ras).ti,ab,kf,rn,nm. (394)

8 incretin mimetic$1.ti,ab,kf,rn,nm. (324)

9 exenatide$.ti,ab,kf,rn,nm. (2693)

10 (ac-2993$2 or ac-2993a$2 or ac002993$2 or ac-002993$2 or ac2993$2 or ac2993a$2 or ac-2993lar$2 or bydureon$ or byetta$ or da-3091$2 or ex4 peptide$2 or exendin$2 or itca-650$2 or ly-2148568$2 or ly2148568$2).ti,ab,kf,rn,nm. (1801)

11 (141732-76-5 or 141758-74-9 or 9p1872d4ol).ti,ab,kf,rn,nm. (2048)

12 Liraglutide/(1130)

13 liraglutide$.ti,ab,kf,rn,nm. (1987)

14 (ideglira$2 or nn-2211$2 or nn-9068$2 or nn2211$2 or nn9068$2 or nn9924$2 or nn-9924$2 or nnc-90-1170$2 or nnc90-1170$2 or saxenda$2 or victoza$2 or xultophy$2).ti,ab,kf,rn,nm. (152)

15 (204656-20-2 or 839I73S42A).ti,ab,kf,rn,nm. (1130)

16 lixisenatide$.ti,ab,kf,rn,nm. (296)

17 (adlyxin$2 or aqve-10010$2 or aqve10010$2 or ave-0010$2 or ave0010$2 or ave-010$2 or ave010$2 or hoe 901$2 or hoe901$2 or iglarlixi$2 or lantus$2 or lixilan$2 or lyxumia$2 or soliqua$2 or suliqua$2 or zp-10$2 or zp10$2).ti,ab,kf,rn,nm. (243)

18 (320367-13-3 or 74O62BB01U).ti,ab,kf,rn,nm. (118)

19 albiglutide$.ti,ab,kf,rn,nm. (140)

20 (albugon$2 or albumin glp 1 or albumin glucagon like peptide 1 or eperzan$2 or glp 1 albumin or glucagon like peptide 1 albumin or gsk-716155$2 or gsk716155$2 or gsk-716155a$2 or gsk716155a$2 or naliglutide$2 or syncria$2 or tanzeum$2).ti,ab,kf,rn,nm. (16)

21 (782500-75-8 or 5E7U48495E).ti,ab,kf,rn,nm. (66)

22 dulaglutide$.ti,ab,kf,rn,nm. (184)

23 (ly2189265$2 or ly-2189265$2 or trulicity$2).ti,ab,kf,rn,nm. (21)

24 (923950-08-7 or WTT295HSY5).ti,ab,kf,rn,nm. (90)

25 semaglutide$.ti,ab,kf,rn,nm. (120)

26 (nn9535$2 or nn-9535$2 or nnc-0113-0217$2 or ozempic$2).ti,ab,kf,rn,nm. (4)

27 (910463-68-2 or 53AXN4NNHX).ti,ab,kf,rn,nm. (19)

28 or/1-27 (12783)

29 Patient Preference/(5997)

30 prefer$.ti,ab,kf. (391979)

31 Choice Behavior/(28476)

32 discrete choice$.ti,ab,kf. (1454)

33 choice experiment$1.ti,ab,kf. (2127)

34 (dce or dces).ti,ab,kf. (4638)

35 discrete rank$.ti,ab,kf. (3)

36 standard gamble$.ti,ab,kf. (785)

37 sg.ti,ab,kf. (8212)

38 time trade off.ti,ab,kf. (1015)

39 tto.ti,ab,kf. (882)

40 willing$.ti,ab,kf. (33298)

41 (wtp or wta or wtt).ti,ab,kf. (1710)

42 conjoint.ti,ab,kf. (2374)

43 contingent valuation$1.ti,ab,kf. (606)

44 (multi-criteria decision$ or multiple-criteria decision$).ti,ab,kf. (562)

45 (mcda or mcdm).ti,ab,kf. (509)

46 (maxdiff or max diff).ti,ab,kf. (18)

47 maximum differential$.ti,ab,kf. (36)

48 ((best$ or worst) adj2 (scaling or scale or scales)).ti,ab,kf. (670)

49 (utility or utilities or hsuv or hsuvs).ti,ab,kf. (169818)

50 or/29-49 (622370)

51 28 and 50 (426)

52 exp animals/not humans/(4430952)

53 51 not 52 (310)

54 limit 53 to (english language and yr=“2005-Current”) (286)

55 remove duplicates from 54 (284)

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