Effect of pill burden on dosing preferences, willingness to pay, and likely adherence among patients with type 2 diabetes

Figures & data

Table 1 Diabetes attributes and levels

Attribute	Levels	Variable name
Reduction in AG (baseline: 206 mg/dL)	66 mg/dL (2.3%)	See notes
	58 mg/dL (2.0%)
	55 mg/dL (1.9%)
	32 mg/dL (1.1%)
	20 mg/dL (0.7%)
Daily dosing schedule	One pill in the morning, one in the evening	DOSE1
	Two pills in the evening	DOSE2
	Two pills in the morning, one in the evening	DOSE3
	Three pills in the morning, three in the evening	DOSE4
Chance of mild-to-moderate stomach problems	10 out of 100 people	STOM1
	23 out of 100 people	STOM2
	25 out of 100 people	STOM3
	30 out of 100 people	STOM4
Hypoglycemia (event)	No hypoglycemic episodes	HYPO1
	One to two hypoglycemic episodes per year	HYPO2
	One to two hypoglycemic episodes per month	HYPO3
	More than two hypoglycemic episodes per month	HYPO4
Weight change within the first 6 months of starting treatment	6 lb weight gain	WGT1
	3 lb weight gain	WGT2
	No weight change	WGT3
	3 lb weight loss	WGT4
	6 lb weight loss	WGT5
Additional chance of CHF	No additional chance of CHF	CHF1
	Additional 1 out of 100 people	CHF2
	Additional 3 out of 100 people	CHF3
Out-of-pocket cost of the medicine	$0 per month	COST1
	$25 per month	COST2
	$100 per month	COST3
	$200 per month	COST4

Note: The additional chance of CHF is the absolute increase in risk above a baseline risk of 8%. Three variables, HIAGRDX, LOAGRDX, and GOOD_CONTROL, were created for the glucose control attribute. HIAGRDX, a continuous variable, was set at the level shown (ie, 55 mg/dL, 58 mg/dL, or 66 mg/dL) in each hypothetical diabetes medicine when a controlled AG was offered (ie, a reduction in AG ≥ 55 mg/dL); otherwise, HIAGRDX was set at 0. Similarly, LOAGRDX, a continuous variable, was set at the level shown (ie, 20 mg/dL or 32 mg/dL) when an uncontrolled AG was offered (ie, a reduction in AG < 55 mg/dL); otherwise, LOAGRDX was set at 0. GOOD_CONTROL, a dummy variable, was equal to one when a controlled AG was offered (ie, a reduction in AG ≥ 55 mg/dL); otherwise, GOOD_CONTROL was set at 0.

Abbreviations: AG, average glucose; CHF, congestive heart failure.

Figure 1 Example choice question.

Abbreviation: CHF, congestive heart failure.

Table 2 Characteristics of the study sample

Characteristic	All patients n = 1,114	Patients with low current-dosing burden n = 90	Patients with high current-dosing burden n = 1,024
Mean age (SD)	62.1 (11.1)	57.0 (11.8)	62.5 (10.9)
Male	599 (53.8%)	49 (54.4%)	550 (53.7%)
Race/ethnicity
White, non-Hispanic	875 (78.5%)	59 (65.6%)	816 (79.7%)
Black, non-Hispanic	126 (11.3%)	21 (23.3%)	105 (10.3%)
Hispanic	55 (4.9%)	6 (6.7%)	49 (4.8%)
Other	58 (5.2%)	4 (4.4%)	54 (5.3%)
Education level
High school diploma or less	311 (27.9%)	29 (32.2%)	282 (27.5%)
More than high school diploma	803 (72.1%)	61 (67.8%)	742 (72.5%)
Marital status
Married or living with partner	759 (68.1%)	62 (68.9%)	697 (68.1%)
Other	355 (31.9%)	28 (31.1%)	327 (31.9%)
Employment status
Employed	410 (36.8%)	43 (47.8%)	367 (35.8%)
Not working	704 (63.2%)	47 (52.2%)	657 (64.2%)
Time since diabetes diagnosis
Less than 1 year ago	29 (2.6%)	6 (6.7%)	23 (2.2%)
1–5 years ago	407 (36.6%)	41 (45.6%)	366 (35.8%)
More than 5 years ago	674 (60.6%)	43 (47.8%)	631 (61.7%)
Don’t know or not sure	3 (0.3%)	0	3 (0.3%)
Missing	1	0	1
Number of prescription medications taken to treat all health condition(s)
Mean (SD)	5.8 (3.6)	2.5 (1.1)	6.1 (3.6)
Missing	9	1	8
Total number of pills taken each day
Mean (SD)	8.8 (6.1)	2.8 (1.0)	9.3 (6.0)
Missing	8	1	7
Number of times each day prescription medications to treat all health condition(s) are taken
Once a day	168 (15.1%)	85 (95.5%)	83 (8.1%)
Twice a day	706 (63.5%)	0	706 (69.0%)
Three times a day	162 (14.6%)	0	162 (15.8%)
As needed	25 (2.2%)	4 (4.5%)	21 (2.1%)
Other	51 (4.6%)	0	51 (5.0%)
Missing	2	1	1

Note: Percentages displayed exclude missing values.

Abbreviation: SD, standard deviation.

Figure 2 Preference weights (n = 1,114).^a

Note: ^aThe vertical bars denote the 95% confidence interval around the point estimate.

Table 3 Willingness to pay for improvements in daily dosing schedule (Us$/month)

Improvements in daily dosing schedule		WTP (95% CI)
From	To	Light users	Heavy users
Two pills in the evening	One pill in the morning, one in the evening	$35.06 ($15.13, $53.91)	$1.50 ($0.11, $8.44)
Two pills in the morning, one in the evening	One pill in the morning, one in the evening	$42.82 ($23.70, $61.01)	$14.91 ($8.05, $25.72)
Three pills in the morning, three in the evening	One pill in the morning, one in the evening	$66.59 ($45.45, $87.09)	$28.99 ($19.38, $38.51)
Two pills in the morning, one in the evening	Two pills in the evening	$8.97 ($0.44, $30.58)	$13.40 ($6.87, $24.12)
Three pills in the morning, three in the evening	Two pills in the evening	$34.89 ($12.74, $56.16)	$27.69 ($18.46, $37.18)
Three pills in the morning, three in the evening	Two pills in the morning, one in the evening	$27.12 ($4.98, $49.42)	$14.70 ($7.31, $25.96)

Abbreviations: CI, confidence interval; WTP, willingness to pay.

Figure 3 Adherence weights (n = 524).^a

Note: ^aThe vertical bars denote the 95% confidence interval around the point estimate.

Table S1 Literature reviewed in determining attributes and levels

Attribute	Publication reviewed
Blood sugar control	Bruce S, Park JS, Fiedorek FT, Howlett HC. Beta-cell response to metformin-glibenclamide combination tablets (Glucovance) in patients with type 2 diabetes. Int J Clin Pract. 2006;60(7):783–790.
	Charbonnel B, Schernthaner G, Brunetti P, et al. Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes. Diabetologia. 2005;48(6):1093–1104.
	Fujioka K, Pans M, Joyal S. Glycemic control in patients with type 2 diabetes mellitus switched from twice-daily immediate release metformin to a once-daily extended-release formulation. Clin Ther. 2003;25:515–529.
	Garber AJ, Donovan DS Jr, Dandona P, Bruce S, Park JS. Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes. J Clin Endocrinol Metab. 2003;88(8):3598–3604.
	Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE; Sitagliptin 036 Study Group. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007;30(8):1979–1987.
	Marre M, Howlett H, Lehert P, Allavoine T. Improved glycaemic control with metformin-glibenclamide combined tablet therapy (Glucovance®) in Type 2 diabetic patients inadequately controlled on metformin. Diabet Med. 2002;19(8):673–680.
	Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP; Sitagliptin Study 024 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulphonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, doubleblind, non-inferiority trial. Diabetes Obes Metab. 2007;9(2):194–205.
	Perez A, Zhao Z, Jacks R, Spanheimer R. Efficacy and safety of pioglitazone/metformin fixed-dose combination therapy compared with pioglitazone and metformin monotherapy in treating patients with T2DM. Curr Med Res Opin. 2009;25(12):2915–2923.
	Rodríguez Á, Ciprés L, Tofé S, Polavieja P, Reviriego J. Clinical evaluation of combined therapy for type 2 diabetes. Curr Med Res Opin. 2010;26(5):1171–1183.
	Umpierrez G, Issa M, Vlajnic A. Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial. Curr Med Res Opin. 2006;22(4):751–759.
Stomach problems	Blonde L, Dailey GE, Jabbour SA, Reasner CA, Mills DJ. Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study. Curr Med Res Opin. 2004;20(4):565–572.
	Feher MD, Al-Mrayat M, Brake J, Leong KS. Tolerability of prolonged-release metformin (Glucophage SR) in individuals intolerant to standard metformin-results from four UK centres. Br J Diabetes Vasc Dis. 2007;7:225–228.
	Fujioka K, Pans M, Joyal S. Glycemic control in patients with type 2 diabetes mellitus switched from twice-daily immediate release metformin to a once-daily extended-release formulation. Clin Ther. 2003;25(2):515–529.
	Gao Y, Li G, Li Y, et al. Postprandial blood glucose response to a standard test meal in insulin-requiring patients with diabetes treated with insulin lispro mix 50 or human insulin mix 50. Int J Clin Practice. 2008;62(9):1344–1351.
	Garber AJ, Duncan TG, Goodman AM, Mills DJ, Rohlf JL. Efficacy of metformin in type II diabetes: results of a doubleblind placebo-controlled dose response trial. Am J Med. 1997;103(6):491–497.
	Garber AJ, Larsen J, Schneider SH, Piper BA, Henry D; Glyburide/Metformin Initial Therapy Study Group. Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes. Diabetes Obes Metab. 2002;4(4):286.
	Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE; Sitagliptin 036 Study Group. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007;30(8):1979–1987.
	Levy J, Cobas RA, Gomes MB. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2010;2:16.
	Schwartz S, Fonseca V, Berner B, Cramer M, Chiang YK, Lewin A. Efficacy, tolerability, and safety of a novel once-daily extended-release metformin in patients with type 2 diabetes. Diabetes Care. 2006;29(4):759–764.
Hypoglycemia	Dibonaventura MD, Wagner JS, Girman CJ, et al. Multinational Internet-based survey of patient preference for newer oral or injectable type 2 diabetes medication. Patient Prefer Adherence. 2010;4:397–406.
	Feher MD, Al-Mrayat M, Brake J, Leong KS. Tolerability of prolonged-release metformin (Glucophage SR) in individuals intolerant to standard metformin-results from four UK centres. Br J Diabetes Vasc Dis. 2007;7:225–228.
Weight change	Dibonaventura MD, Wagner JS, Girman CJ, et al. Multinational internet-based survey of patient preference for newer oral or injectable type 2 diabetes medication. Patient Prefer Adherence. 2010;4:397–406.
	Feher MD, Al-Mrayat M, Brake J, Leong KS. Tolerability of prolonged-release metformin (Glucophage SR) in individuals intolerant to standard metformin-results from four UK centres. Br J Diabetes Vasc Dis. 2007;7:225–228.
Congestive heart failure	Home PD, Pocock SJ, Beck-Nielsen H, et al; RECORD Study Team. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 2009;373(9681):2125–2135.