Treatment outcomes after initiation of exenatide twice daily or insulin in clinical practice: 12-month results from CHOICE in six European countries

Figures & data

Table 1 Baseline clinical and demographic characteristics of patients initiated on exenatide twice daily (BID) or insulin therapy for the total CHOICE cohort²⁷ and propensity-matched subgroup

Variable	Total cohort			Matched subgroup ^a
	Exenatide BID (n = 1177)	Insulin (n = 1315)	P	Exenatide BID (n = 570)	Insulin (n = 570)
Male, n (%)	635 (54.0)	762 (57.9)	0.0427	311 (54.6)	330 (57.9)
Caucasian, n (%)	970 (82.4)	1206 (91.7)	NS	NA	NA
Age, years	58.0 (10.1)	63.7 (10.9)	<0.0001	60.4 (10.2)	60.7 (10.2)
Weight, kg	101.1 (21.6)	84.3 (17.6)	<0.0001	92.7 (17.3)	92.0 (17.9)
BMI, kg/m^2	35.3 (6.5)	29.7 (5.4)	<0.0001	32.6 (5.1)	32.3 (5.5)
Waist circumference, cm	114.6 (14.8)	103.3 (14.1)	<0.0001	110.0 (13.5)	108.4 (13.7)
Systolic blood pressure, mmHg	137.8 (16.5)	137.4 (17.4)	NS	137.7 (16.7)	137.5 (16.5)
Diastolic blood pressure, mmHg	81.6 (9.6)	80.1 (9.9)	<0.0001	80.6 (9.5)	80.5 (10.2)
HbA1c, most recent in previous	8.4 (1.4)	9.2 (1.9)	<0.0001	8.7 (1.5)	8.6 (1.5)
3 months, %
Concomitant therapy, n (%)
Lipid-lowering	664 (56.4)	712 (54.1)	NS	NA	NA
Cardiovascular	895 (76.0)	972 (73.9)	NS	NA	NA
Antiplatelet	485 (41.2)	599 (45.6)	NS	NA	NA
Weight-lowering	54 (4.6)	20 (1.5)	<0.0001	NA	NA
Time since diabetes diagnosis, years	8 (6)	10 (7)	<0.0001	NA	NA
Antidiabetic medication class used (previous 12 months), n (%)
Alpha-glucosidase inhibitor	15 (1.3)	21 (1.6)	–	NA	NA
Biguanide	816 (69.3)	881 (67.0)	–	NA	NA
Biguanide + sulfonylurea	33 (2.8)	39 (3.0)	–	NA	NA
DPP-4 inhibitor	81 (6.9)	97 (7.4)	–	NA	NA
GLP-1 receptor agonist	2 (0.2)	0 (0.0)	–	NA	NA
Secretion enhancer (nateglinide or repaglinide)	75 (6.4)	99 (7.5)	–	NA	NA
Sulfonylurea	494 (42.0)	682 (51.9)	–	NA	NA
Thiazolidinedione	136 (11.6)	150 (11.4)	–	NA	NA
Thiazolidinedione + biguanide	66 (5.6)	39 (3.0)	–	NA	NA
Thiazolidinedione + sulfonylurea	2 (0.2)	1 (0.1)	–	NA	NA
Other	3 (0.3)	4 (0.3)	–	NA	NA
Diabetes complications, n (%)				NA	NA
≥ 1 macrovascular complication	212 (18.0)	339 (25.8)	<0.0001	NA	NA
≥ 1 microvascular complication	173 (14.7)	281 (21.4)	<0.0001	NA	NA

Notes: Continuous data presented are means (standard deviation). The Wilcoxon test was used for continuous data. The Chi-square or Fisher’s exact test were used for categorical data.

a There were no statistically significant differences between the cohorts in the matched subgroup, with the exception of waist circumference (P = 0.0320).

Abbreviations: BMI, body mass index; DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1; HbA_1c, glycated hemoglobin; NA, data not available; NS, nonsignificant (using a threshold for statistical significance of P < 0.05).

Figure 1 Study disposition.

Note: ^aEvaluable patients were required to provide informed consent and fulfill all study entry criteria as well as have ≥1 post-baseline assessment.

Figure 2 Kaplan–Meier estimates for time until significant treatment change after the initiation of first injectable therapy for the exenatide twice-daily (BID) cohort and total insulin cohort. The estimated number of patients remaining in the study with no significant treatment change is provided above each period.

Notes: *For exenatide BID: at 3 months, 88.7% (95% CI: 86.8%, 90.6%) of patients had no significant treatment change; at 6 months, 79.2% (76.8%, 81.6%) had no significant treatment change; at 12 months, 67.8% (64.9%, 70.7%) had no significant treatment change. For insulin: at 3 months, 85.5% (95% CI: 83.5%, 87.5%) of patients had no significant treatment change; at 6 months 78.0% (95% CI: 75.6%, 80.3%) had no significant treatment change; at 12 months 70.9% (68.3%, 73.5%) had no significant treatment change.
Abbreviation: CI, confidence interval.

Table 2 Treatment change occurring during the 12 months following initiation of exenatide twice daily (BID) and insulin in patients with type 2 diabetes mellitus ^a

Variable	Exenatide BID (n = 1096)	Insulin (n = 1239)
≥1 significant treatment change, n (%)	349 (31.8)	357 (28.8)
First significant treatment change, n (%)
Addition of a new medication (any route of administration) for the treatment of type 2 diabetes ^b	175 (16.0)	251 (20.3)
Addition of a new oral medication	86 (7.8)	44 (3.6)
Addition of a new injectable medication	96 (8.8)	208 (16.8)
Change to the number of times insulin was administered per day	NA	71 (5.7)
Substitution of a human insulin for an analog insulin or vice versa	NA	17 (1.4)
Discontinuation of any injectable medication initiated at baseline	269 (24.5)	80 (6.5)
Any significant treatment change, n (%)
Addition of a new medication (any route of administration) for the treatment of type 2 diabetes	265 (24.2)	289 (23.3)
Addition of a new oral medication	115 (10.5)	60 (4.8)
Addition of a new injectable medication	182 (16.6)	244 (19.7)
Change to the number of times insulin was administered per day	NA	94 (7.6)
Substitution of a human insulin for an analog insulin or vice versa	NA	25 (2.0)
Discontinuation of any injectable medication initiated at baseline ^c	287 (26.2)	101 (8.2)
Reasons for discontinuation, n (%)
Inadequate response	107 (9.8)	59 (4.8)
Adverse event	80 (7.3)	4 (0.3)
Noncompliance	7 (0.6)	2 (0.2)
Subject decision	49 (4.5)	12 (1.0)
Cannot afford medication	4 (0.4)	1 (0.1)
Other	40 (3.6)	23 (1.9)

Notes:

a Addition of oral antidiabetic drugs within the first 4 weeks after initiation of injectable therapy was considered part of initial treatment titration and did not count as a significant treatment change;

b patients could initiate ≥ 1 new therapies;

c a total of 285 patients discontinued exenatide BID.

Abbreviations: BID, twice daily; NA, not applicable.

Table 3 Mean changes in clinical variables from baseline to 12 months (for patients with data at 12 months) after initiation of exenatide twice daily (BID) or insulin in patients with type 2 diabetes mellitus – initiators population

Variable	Exenatide BID	Insulin
HbA1c, n	871	1009
% units (SD; 95% CI)	−1.0 (1.4; −1.1, −0.9)	−1.8 (1.8; −1.9, −1.7)
Body weight, n	915	1045
kg (SD; 95% CI)	−3.3 (5.9; −3.7, −2.9)	1.9 (4.9; 1.6, 2.1)
Body weight according to insulin type, kg (SD; 95% CI)
Basal bolus (n = 166)	NA	2.4 (6.5; 1.3, 3.5)
Long acting only (n = 618)	NA	1.6 (4.2; 1.2, 1.9)
Mixtures only (n = 303)	NA	1.8 (5.2; 1.2, 2.4)
Short acting only (n = 135)	NA	2.8 (4.8; 1.9, 3.6)
Other (n = 14)	NA	1.3 (4.4; −1.6, 4.3)
BMI, n	906	1042
kg/m^2 (SD; 95% CI)	−1.2 (2.1; −1.3, −1.0)	0.7 (1.7; 0.6, 0.8)
Waist circumference, n	651	742
cm (SD; 95% CI)	−2.5 (8.9; −3.2, −1.8)	1.4 (9.0; 0.7, 2.0)
Blood pressure, n	858	963
Systolic, mmHg (SD; 95% CI)	−2.4 (17.2; −3.6, −1.3)	−2.5 (18.5; −3.6, −1.3)
Diastolic, mmHg (SD; 95% CI)	−1.6 (10.8; −2.3, −0.8)	−1.8 (11.1; −2.5, −1.1)
Plasma lipids, mmol/L (SD; 95% CI)
Total cholesterol, n	692	789
	−0.2 (1.0; −0.3, −0.1)	−0.3 (1.1; −0.3, −0.2)
LDL cholesterol, n	640	733
	−0.1 (0.9; −0.2, −0.0)	−0.2 (0.9; −0.3, −0.1)
HDL cholesterol, n	658	753
	0.0 (0.3; 0.0, 0.1)	0.1 (0.3; 0.0, 0.1)
Triglycerides, n	675	773
	−0.3 (1.4; −0.4, −0.2)	−0.4 (1.6; −0.5, −0.3)

Note: Continuous data are means (SD; 95% CI).

Abbreviations: BMI, body mass index; CI, confidence interval; HbA_1c, glycated hemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NA, not applicable; SD, standard deviation.

Table 4 Hypoglycemia occurring between baseline and 12 months (or time of study discontinuation, if earlier than 12 months) after initiation of exenatide twice daily (BID) or insulin in patients with type 2 diabetes mellitus – initiators population

Variable	Exenatide BID (n = 1096)	Insulin (n = 1239)
Patients with ≥1 hypoglycemic event, n (%)
Total	145 (13.2)	354 (28.6)
Nocturnal hypoglycemia	24 (2.2)	140 (11.3)
Daytime hypoglycemia	131 (12.0)	318 (25.7)
Events resolved by patient alone	140 (12.8)	345 (27.8)
Total events requiring third-party assistance but not hospitalization	5 (0.5)	50 (4.0)
Events requiring a visit to the emergency room	2 (0.2)	8 (0.6)
Events requiring admission to hospital	2 (0.2)	7 (0.6)
Severe hypoglycemia ^a	7 (0.6)	54 (4.4)
Patients receiving sulfonylureas	(n = 587)	(n = 602)
Patients with ≥1 hypoglycemic event, (%)	120 (20.4)	197 (32.7)
Patients not receiving sulfonylureas	(n = 509)	(n = 637)
Patients with ≥1 hypoglycemic event, n (%)	25 (4.9)	157 (24.6)
Number of hypoglycemic events among patients with ≥1 episode, mean (SD; 95% CI)
Total	6.0 (8.5; 4.6, 7.5) ^b	7.7 (21.8; 5.4, 10.0) ^c
Nocturnal hypoglycemia	2.6 (3.5; 1.1, 4.1)	2.8 (3.1; 2.3, 3.3)
Daytime hypoglycemia	6.1 (8.5; 4.6, 7.5)	7.2 (22.2; 4.7, 9.6)
Events resolved by patient alone	6.1 (8.5; 4.6, 7.5)	7.4 (21.8; 5.1, 9.7)
Events requiring third-party assistance but not hospitalization	1.6 (1.3; −0.1, 3.3)	1.8 (1.6; 1.3, 2.3)
Events requiring a visit to the emergency room	1.0 (0.0; −)	1.1 (0.4; 0.8, 1.4)
Events requiring admission to hospital	1.0 (0.0; −)	1.0 (0.0; −)
Severe hypoglycemia ^a	1.7 (1.1; 0.7, 2.7)	2.0 (1.6; 1.5, 2.4)
In patients receiving sulfonylureas	6.0 (8.4; 4.5, 7.5)	5.9 (7.5; 4.8, 7.0)
In patients not receiving sulfonylureas	6.2 (9.0; 2.4, 10.0)	9.9 (31.4; 4.9, 14.9)
Rate of hypoglycemic events in each treatment cohort
Number per 100 patients per 30 days (SD; 95% CI)	7.4 (36.2; 5.5, 10.3)	19.5 (125.1; 14.9, 33.4)

Notes:

a “Severe hypoglycemic events” were defined as those requiring third-party assistance, an emergency room visit, and/or hospital admission. Confirmation by blood glucose monitoring was not a study requirement;

b the mean (SD; 95% CI) number of events confirmed by blood glucose monitoring was 5.8 (8.0; 4.4, 7.3); confirmation by blood glucose monitoring was not a study requirement;

c the mean (SD; 95% CI) number of events confirmed by blood glucose monitoring was 6.6 (14.3; 4.9, 8.2); confirmation by blood glucose monitoring was not a study requirement.

Abbreviations: CI, confidence interval; SD, standard deviation.

Table 5 Gastrointestinal (GI) events occurring during the 12 months (or time of study discontinuation, if earlier than 12 months) following initiation of exenatide twice daily (BID) and insulin in patients with type 2 diabetes mellitus – initiators population

Variable	Exenatide BID (n = 1096)	Insulin (n = 1239)
Patients with ≥1 GI symptom,	305 (27.8)	43 (3.5)
n (%)
1 symptom	186 (17.0)	28 (2.3)
2 symptoms	67 (6.1)	8 (0.6)
3 symptoms	29 (2.6)	5 (0.4)
≥ 4 symptoms	23 (2.1)	2 (0.2)
Type of GI event, n (%)
Nausea	165 (15.1)	7 (0.6)
Abdominal pain	62 (5.7)	21 (1.7)
Fullness/early satiety	68 (6.2)	5 (0.4)
Vomiting	62 (5.7)	3 (0.2)
Heartburn	41 (3.7)	15 (1.2)
Anorexia	22 (2.0)	1 (0.1)
Taste changes	11 (1.0)	1 (0.1)

Figure 3 The incidence of gastrointestinal (GI) events after initiation of exenatide twice daily (BID) or insulin in patients with type 2 diabetes mellitus.

Figure 4 Change in glycated hemoglobin (HbA_1c) according to the type of first insulin therapy initiated during the 12 months following initiation of that therapy.

Matthaei S Reaney M Mathieu C Patients with Type 2 Diabetes Initiating Exenatide Twice Daily or Insulin in Clinical Practice: CHOICE Study Diabetes Ther 2012 3 1 6 22714818

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