Evaluating the Impact of Therapy on Quality of Life in Type 2 Diabetes: A Literature Review of Utilities Associated with Treatment-Related Attributes

Figures & data

Table 1 Summary of Included Studies

Study	Population	N	Instrument Used	Treatment-Related Characteristics/Process Attributes
Adibe et al. 2013 (Nigeria)^Citation7	Adults with T2D	638	HUI-2, HUI-3	Treatment modality (insulin use)
Al-Aboudi et al. 2015 (Saudi Arabia)^Citation8	Adults with T2D	75	EQ-5D-3L	Treatment modality (diet only, OADs, insulin)
Boye et al. 2011 (UK)^Citation9	Adults with T2D (aged 30–75 years)	151	SG	Dosing flexibility, dosing frequency, injection site reaction
Boye et al. 2019 (Italy)^Citation10	Adults with T2D (aged 30–75 years)	216	TTO	Oral treatment, injectable treatment (dulaglutide or semaglutide, based on device and administration procedure)
Boye et al. 2020 (UK)^Citation11	Adults with T2D	201	TTO	Oral treatment (simple oral treatment versus oral treatment with specific dosing instructions), injection (weekly, semaglutide versus dulaglutide)
Butt et al. 2018 (Malaysia)^Citation12	Adults with T2D (poorly controlled)	56	EQ-5D-3L	Treatment modality (OADs, insulin)
Kamradt et al. 2017 (Germany)^Citation13	Adults with T2D (with ≥2 other co-morbid conditions)	404	EQ-5D-3L	Change in BMI
Kiadaliri et al. 2014 (Sweden)^Citation14	Adults with T2D	1757	EQ-5D-3L	BMI increase, treatment modality (diet/exercise, OADs, insulin)
Kontodimopolous et al. 2012 (Greece)^Citation15	Adults with T2D	319	EQ-5D-3L, SF-6D, 15D	Change in BMI
Lane et al. 2014 (Canada)^Citation16	Adults with T2D (treated with OADs)	96	TTO	Weight loss and gain, change in BMI
Lin et al. 2018 (Taiwan)^Citation17	Adults with T2D	213	SG and VAS	Treatment-related adverse events, UTI, mycotic genital infection
Luk et al. 2014 (China)^Citation18	Adults with T2D	14,826	EQ-5D-3L	Treatment modality (insulin)
Matza et al. 2017 (UK)^Citation19	Adults with T2D (aged 30–75 years)	209	TTO	Oral treatment, injection related attributes (reconstitution, waiting, needle handling)
Matza et al. 2018 (Italy)^Citation20	Adults with T2D (aged 30–75 years)	238	TTO	Oral treatment, injection related attributes (reconstitution, waiting, needle handling)
Matza et al. 2018 (Italy)^Citation21	Adults with T2D	191	TTO	Insulin treatment (attribute based, concentration/volume, ease of injection, number of pens required)
Nauck et al. 2019 (Multinational)^Citation22	Adults with T2D at high risk of cardiovascular disease	3014	EQ-5D-3L	Weight loss, treatment modality (insulin initiation)
Nguyen et al. 2018 (Vietnam)^Citation23	Adults with T2D (aged ≥60 years)	171	EQ-5D-3L	Treatment modality (insulin initiation)
Olofsson et al. 2016 (Sweden)^Citation24	General population	979	TTO	Weight gain (insulin-related), insulin dosing frequency
O’Shea et al. 2015 (Ireland)^Citation25	Adults with T2D (aged 25–80 years)	159	EQ-5D	Treatment modality (diet/OADs, insulin, non-insulin injectables)
Polster et al. 2010 (Not reported)^Citation26	Adults with T2D	382	TTO	Dosing frequency/flexibility, treatment-related adverse events (nausea)
Quah et al. 2011 (Singapore)^Citation27	Adults with T2D	699	EQ-5D-3L	Treatment modality (OADs, insulin)
Rajan et al. 2016 (South Korea and Taiwan)^Citation28	General population	59	SG	Weight loss, weight gain, dosing frequency, nausea
Riddlestrale et al. 2016 (UK, Sweden, Denmark)^Citation29	General public (UK, Denmark), adults with T2D (Sweden)	1777 (UK), 1779 (Denmark), 484 (Sweden)	TTO	Weight change, BMI change, dosing frequency
Romero-Naranjo et al. 2019 (Ecuador)^Citation30	Adults with T2D	325	EQ-5D-3L	Treatment modality (OADs, insulin)
Schunk et al. 2015 (Germany)^Citation31	Adults with T2D (aged 45–74 years)	846	SF-6D	Treatment modality (OADs, insulin)
Shim et al. 2012 (Singapore)^Citation32	Adults with T2D	282	EQ-5D	Treatment modality (insulin)
Shingler et al. 2015 (UK)^Citation33	General public	100	TTO	Treatment related AEs (GI symptoms, UTI, mycotic infection, hypovolemic event)
Solli et al. 2010 (Norway)^Citation34	Adults with T2D	356	EQ-5D	Increase in BMI
Wan et al. 2016 (China)^Citation35	Adults with T2D	1826	SF-6D	Treatment modality (insulin)
Zhang et al. 2012 (USA)^Citation36	Adults with T2D	7327	EQ-5D	Treatment modality (insulin)

Abbreviations: AE, adverse event; BMI, body mass index; EQ-5D, EuroQol 5-dimensions; GI, gastrointestinal; HUI2, Health Utilities Index-2; HUI3, Health Utilities Index-3; OADs, oral antidiabetic agents, SF-6D, Short form 6 dimensions; SG, standard gamble; T2D, type 2 diabetes; TTO, time tradeoff; UTI, urinary tract infection; VAS, visual analog scale.

Figure 1 Summary of literature review process.

Abbreviation: T2D, type 2 diabetes.

Table 2 Influence of Change in Body Weight and Change in BMI in T2D on Utility Scores

Health State	Study (Country)	Method	Population	Disutility	SE	95% CI
BMI
1-unit increase	Kamradt et al. 2017 (Germany)^Citation13	EQ-5D-3L	T2D	−0.0047	0.0016
	Kiadaliri et al. 2014 (Sweden)^Citation14	EQ-5D-3L	T2D	−0.0060^a
	Kiadaliri et al. 2014 (Sweden)^Citation14	EQ-5D-3L	T2D	−0.0027^b
	Kontodimopoulos et al. 2012 (Greece)^Citation15	EQ-5D-3L	T2D	−0.006	0.002
	Kontodimopoulos et al. 2012 (Greece)^Citation15	15D	T2D	−0.003	0.001
	Lane et al. 2014 (Canada)^Citation16	TTO	T2D	−0.0472		−0.0569 to −0.0375
	Solli et al. 2010 (Norway)^Citation34	EQ-5D	T2D	−0.002		−0.007 to 0.002
1-unit decrease	Lane et al. 2014 (Canada)^Citation16	TTO	T2D	+0.0171		−0.0103 to 0.0238
1-unit change	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	UK general population	0.021		0.018 to 0.023^c
	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	Denmark general population	0.012		0.011 to 0.014^c
	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	Sweden T2D	0.021		0.017 to 0.024^c
Weight change
−3%	Lane et al. 2014 (Canada)^Citation16	TTO	T2D	+0.012
	Rajan et al. 2016 (South Korea, Taiwan)^Citation28	SG	General population	+0.028
−5%	Lane et al. 2014 (Canada)^Citation16	TTO	T2D	+0.029
	Nauck et al. 2019 (Multinational)^Citation22	EQ-5D-3L	T2D	+0.008^d		−0.001 to 0.016^d
	Rajan et al. 2016 (South Korea, Taiwan)^Citation28	SG	General population	+0.029
−7%	Lane et al. 2014 (Canada)^Citation16	TTO	T2D	+0.037
+3%	Lane et al. 2014 (Canada)^Citation16	TTO	T2D	−0.004
	Rajan et al. 2016 (South Korea, Taiwan)^Citation28	SG	General population	0
+5%	Lane et al. 2014 (Canada)^Citation16	TTO	T2D	−0.047
	Rajan et al. 2016 (South Korea, Taiwan)^Citation28	SG	General population	−0.001
+7%	Lane et al. 2014 (Canada)^Citation16	TTO	T2D	−0.106
+1 kg	Olofsson et al. 2016 (Sweden)^Citation24	TTO	General population	−0.010^e,f
+3 kg	Olofsson et al. 2016 (Sweden)^Citation24	TTO	General population	+0.011^e,f
+1 kg	Olofsson et al. 2016 (Sweden)^Citation24	TTO	General population	+0.008^f,g
+3 kg	Olofsson et al. 2016 (Sweden)^Citation24	TTO	General population	+0.020^f,g
±1 kg	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	UK general population	0.0073		0.0065 to 0.0081^c
	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	Denmark general population	0.0041		0.0036 to 0.0046^c
	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	Sweden T2D	0.0068		0.0057 to 0.0081^c

Notes: ^aUK tariff. ^bSwedish tariff. ^cRange low 2.5% to high 97.5. ^dWeight loss of 5% from baseline during 36-month follow-up period, change. ^eCombination of 1 fixed injection plus weight gain basal insulin only. ^fUtility benefit associated with avoiding 1/3 kg weight gain. ^gCombination of 1 fixed injection plus weight gain basal bolus insulin.

Abbreviations: BMI, body mass index; CI, confidence interval; SE, standard error; SG, standard gamble; TTO, time trade off.

Table 3 Influence of Dosing Frequency and Flexibility on Utility Scores

Health State	Study (Country)	Method	Population	Disutility	SD	95% CI
Weekly versus daily injection	Boye et al. 2011 (UK)^Citation9	SG	T2D	+0.023	0.158
Dosing timing flexibility	Boye et al. 2011 (UK)^Citation9	SG	T2D	+0.006	0.158
Weekly versus daily injection	Rajan et al. 2016 (South Korea, Taiwan)^Citation28	SG	General population	+0.043
Once daily flexible dosing versus twice daily fixed dosing	Polster et al. 2010 (not reported)^Citation26	TTO	T2D	+0.005
Insulin once daily versus twice daily	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	UK general population	+0.020		0.010 to 0.031^a
		TTO	Denmark general population	+0.021		0.014 to 0.027^a
		TTO	Sweden T2D	+0.015		0.0001 to 0.029^a
Once daily versus twice daily planning	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	UK general population	+0.046		0.035 to 0.058^a
		TTO	Denmark general population	+0.043		0.036 to 0.051^a
		TTO	Sweden T2D	+0.038		0.021 to 0.054^a
Once daily versus four times daily planning	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	UK general population	+0.070		0.057 to 0.082^a
		TTO	Denmark general population	+0.084		0.075 to 0.093^a
		TTO	Sweden T2D	+0.109		0.086 to 0.133^a
Twice daily versus twice daily planning	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	UK general population	+0.026		0.014 to 0.037^a
		TTO	Denmark general population	+0.022		0.015 to 0.030^a
		TTO	Sweden T2D	+0.023		0.006 to 0.040^a
Twice daily versus four times daily planning	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	UK general population	+0.049		0.037 to 0.062^a
		TTO	Denmark general population	+0.064		0.055 to 0.072^a
		TTO	Sweden T2D	+0.095		0.071 to 0.118^a
Twice daily planning versus four times daily planning	Riddlestrale et al. 2016 (UK, Denmark, Sweden)^Citation29	TTO	UK general population	+0.023		0.010 to 0.037^a
		TTO	Denmark general population	+0.041		0.031 to 0.051^a
		TTO	Sweden T2D	+0.071		0.047 to 0.096^a
1 less injection per day	Olofsson et al. 2016 (Sweden)^Citation24	TTO	General population	+0.036^b, +0.037^c
Time flexibility with injection	Olofsson et al. 2016 (Sweden)^Citation24	TTO	General population	+0.011^b, +0.010^c
1 less injection and time flexibility	Olofsson et al. 2016 (Sweden)^Citation24	TTO	General population	+0.047^b, +0.048^c

Notes: ^aRange low 2.5% to high 97.5%. ^bBasal only. ^cBasal bolus.

Abbreviations: CI, confidence interval; SE, standard error; SG, standard gamble; TTO, time tradeoff; T2D, type 2 diabetes.

Table 4 Influence of Device-Related Attributes and Process Characteristics on Utility Scores

Study (Country)	Attribute	Method	Population	Mean	SD	95% CI	Disutility	SD
Boye et al. 2011 (UK)^Citation9	Utility benefit once weekly dosing (vs daily) dosing and injection site reaction, flexible dose	SG	T2D				+0.021	0.160
	Utility benefit once weekly dosing (vs daily) dosing and no injection site reaction, flexible dose	SG	T2D				+0.024	0.156
	Utility benefit once weekly dosing (vs daily) dosing and injection site reaction, not flexible dose	SG	T2D				+0.024	0.161
	Utility benefit once weekly dosing (vs daily) dosing and no injection site reaction, not flexible dose	SG	T2D				+0.022	0.156
	Injection site reaction, injection every day, flexible dose	SG	T2D	0.856	0.166		−0.010	0.165
	Injection site reaction, injection once a week, flexible dose	SG	T2D	0.877	0.153		−0.013	0.150
	Injection site reaction, injection every day, dosing not flexible	SG	T2D	0.848	0.169		−0.012	0.165
	Injection site reaction, injection once a week, dosing not flexible	SG	T2D	0.873	0.152		−0.010	0.151
	Flexible dosing plus injection site reaction, daily injection	SG	T2D				+0.007	0.167
	Flexible dosing plus injection site reaction, once weekly injection	SG	T2D				+0.005	0.153
	Flexible dosing plus no injection site reaction, daily dosing	SG	T2D				+0.006	0.163
	Flexible dosing plus no injection site reaction, once weekly dosing	SG	T2D				+0.008	0.149
Boye et al. 2019 (Italy)^Citation10	OAD plus weekly dulaglutide injection (dulaglutide injection device)	TTO	T2D	0.894	0.085	0.882 to 0.905	+0.007^a	0.019^a
	OADs plus weekly semaglutide injection (semaglutide injection device)	TTO	T2D	0.887	0.087	0.875 to 0.898
Boye et al. 2020 (UK)^Citation11	Weekly dulaglutide injection	TTO	T2D	0.878
	Weekly semaglutide injection	TTO	T2D	0.859
Matza et al. 2017 (UK)^Citation19	Weekly injection, reconstitution, waiting, needle handling	TTO	T2D	0.858	0.165		−0.030^b, −0.020^c	0.073^b, 0.042^c
	Reconstitution, waiting	TTO	T2D	0.863	0.161		−0.025^b, −0.014^c	0.066^b, 0.032^c
	Reconstitution, needle handling	TTO	T2D	0.868	0.159		−0.020^b, −0.010^c	0.063^b, 0.027^c
	Reconstitution	TTO	T2D	0.874	0.157		−0.014^b, −0.004^c	0.058^b, 0.016^c
	Needle handling	TTO	T2D	0.874	0.156		−0.014^b, −0.004^c	0.058^b, 0.015^c
	Weekly injection, no inconvenience	TTO	T2D	0.878	0.156		−0.010^b	0.056^b
Matza et al. 2018 (Italy)^Citation20	Weekly injection, reconstitution, waiting, needle handling	TTO	T2D	0.868	0.109		−0.032^b, −0.022^c	0.059^b, 0.052^c
	Reconstitution, waiting	TTO	T2D	0.872	0.109		−0.027^b, −0.018^c	0.058^b, 0.052^c
	Reconstitution, needle handling	TTO	T2D	0.879	0.102		−0.020^b, −0.011^c	0.040^b, 0.030^c
	Reconstitution	TTO	T2D	0.884	0.100		−0.015^b, −0.006^c	0.032^b, 0.021^c
	Needle handling	TTO	T2D	0.884	0.101		−0.016^b, −0.006^c	0.033^b, 0.021^c
	Weekly injection, no inconvenience	TTO	T2D	0.890	0.100		−0.009^b	0.025^b
Matza et al. 2020 (Italy)^Citation21	Standard insulin	TTO	T2D	0.882	0.104	0.867 to 0.897
	Concentrated insulin (less injection volume, less effort to press injection button and fewer pens required)	TTO	T2D	0.889	0.103	0.875 to 0.904

Notes: ^aBenefit associated with dulaglutide versus semaglutide device. ^bVersus oral treatment. ^cVersus weekly injection with no inconvenience.

Abbreviations: CI, confidence interval; OAD, oral antidiabetic drug; SD, standard deviation; SG, standard gamble; T2D, type 2 diabetes; TTO, time trade off.

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