Dulaglutide as an Add-on to Insulin in Type 2 Diabetes; Clinical Efficacy and Parameters Affecting the Response in Real-World Practice

Figures & data

Table 1 Baseline Characteristics of the Study Participants, Classified According to Their Change in HbA1c

Parameter	All Participants (n=120)	HbA1c Change
		≥ 1% (n = 56)	< 1% (n = 64)	P value
Age, yr	55.1 ± 11.0	57.2 ± 11.1	53.3 ± 10.7	0.052
Sex, male	69 (57.5)	35 (62.5)	34 (53.1)	0.300
T2DM duration, yr	17.2 ± 8.3	17.2 ± 9.2	17.1 ± 7.4	0.936
Body mass index, kg/m^2	27.5 ± 3.6	28.1 ± 3.7	26.9 ± 3.5	0.062
Total daily insulin dose, IU	47.8 ± 25.6	49.0 ± 30.2	46.7 ± 21.0	0.637
HbA1c, %	9.1 ± 1.7	10.0 ± 1.4	8.3 ± 1.5	< 0.001
FPG, mg/dL	168.6 ± 64.7	183.2 ± 68.5	155.9 ± 58.8	0.021
PP2, mg/dL^a	253.6 ± 92.5	251.7 ± 98.2	255.9 ± 86.3	0.847
Fasting C-peptide, ng/mL^a	2.1 ± 1.6	2.0 ± 1.3	2.2 ± 1.8	0.697
Total cholesterol, mg/dL	154.9 ± 40.2	155.8 ± 44.9	154.2 ± 35.9	0.834
Triglycerides, mg/dL	169.2 ± 92.5	176.9 ± 95.2	162.6 ± 90.5	0.405
HDL-cholesterol, mg/dL	45.5 ± 11.3	44.7 ± 11.6	46.2 ± 11.0	0.473
LDL-cholesterol, mg/dL	98.0 ± 31.4	101.9 ± 35.8	96.5 ± 27.0	0.367
BUN, mg/dL	18.8 ± 8.9	19.3 ± 10.6	18.4 ± 7.1	0.609
Creatinine, mg/dL	0.98 ± 0.36	1.01 ± 0.40	0.94 ± 0.31	0.282
eGFR, mL/min/1.73 m^2	82.7 ± 23.7	80.8 ± 25.4	84.4 ± 22.2	0.416
AST, IU/L	26.2 ± 14.1	28.5 ± 17.0	24.2 ± 10.6	0.096
ALT, IU/L	27.6 ± 20.1	31.0 ± 23.3	24.6 ± 16.5	0.081
Urine ACR, mg/g Cr^a	625.7 ± 1621.5	835.9 ± 2167.8	439.7 ± 877.2	0.214
Dulaglutide dose, n				0.024
0.75 mg	38 (31.7)	12 (21.4)	26 (40.6)
1.5 mg	82 (68.3)	44 (78.6)	38 (59.4)
Hypertension	73 (60.8)	34 (60.7)	39 (60.9)	0.980
Dyslipidemia	101 (84.2)	46 (82.1)	55 (85.9)	0.570

Notes: Data are presented as means ± standard deviation or as n (%). ^aPP2 concentrations were not available for 42 participants. Fasting C-peptide levels were not available for ten patients. Urine ACRs were not available for five participants.

Abbreviations: T2DM, type 2 diabetes mellitus; IU, international units; FPG, fasting plasma glucose; PP2, postprandial 2 h glucose; HDL/LDL, high-density/low-density lipoprotein; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; AST/ALT, aspartate/alanine aminotransferase; ACR, albumin/creatinine ratio.

Figure 1 Measures of therapeutic efficacy of add-on dulaglutide over 6 months (A) HbA1c, (B) fasting plasma glucose, (C) body weight, and (D) total daily insulin dose. Data are presented as mean ± standard error (SE); ***P < 0.001 versus baseline; **P < 0.01.

Table 2 Univariate Linear Regression Analysis of the Reduction in HbA1c

Parameter	Standardized ß	95% CI	p value
Age, yr	−0.012	−0.041 to 0.016	0.392
Sex, female	0.430	−0.202 to 1.062	0.181
Baseline HbA1c, %	−0.663	−0.802 to −0.524	< 0.001
Baseline FPG, mg/dL	−0.008	−0.012 to −0.003	0.002
C-peptide, ng/mL	−0.019	−0.234 to 0.196	0.861
Baseline body weight, kg	−0.014	−0.039 to 0.011	0.283
Baseline BMI, kg/m^2	−0.066	−0.152 to 0.021	0.136
T2DM duration, yr	0.008	−0.030 to 0.046	0.674
Total daily insulin dose at baseline, IU^a	0.001	−0.011 to 0.013	0.868
Changes in total daily insulin dose, IU	0.013	−0.007 to 0.033	0.192
eGFR, mL/min/1.73m^2	0.002	−0.011 to 0.016	0.717
Hypertension	0.191	−0.453 to 0.836	0.558
Dyslipidemia	0.091	−0.772 to 0.954	0.835

Note: ^aChanges in total daily insulin dose were measured between the total daily insulin dose at baseline and the total daily insulin dose after 6 months.

Abbreviations: CI, confidence interval; HbA1c, glycated hemoglobin; FPG, fasting plasma glucose; T2DM, type 2 diabetes mellitus; IU, international units; BMI, body mass index; GFR, glomerular filtration rate.

Table 3 Multiple Linear Regression Analysis of the Reduction in HbA1c

Parameter	Standardized ß	95% CI	p value
Age, yr	−0.012	−0.036 to 0.012	0.320
Sex, female	0.460	−0.045 to 0.965	0.074
Baseline HbA1c, %	−0.699	−0.847 to −0.551	< 0.001
Baseline body weight, kg	−0.010	−0.032 to 0.012	0.361
Change in total daily insulin dose, IU^a	−0.012	−0.028 to 0.005	0.167

Note: ^aChanges in total daily insulin dose were measured between the total daily insulin dose at baseline and the total daily insulin dose after 6 months.

Abbreviations: CI, confidence interval; HbA1c, glycated hemoglobin; T2DM, type 2 diabetes mellitus; IU, international units.

Figure 2 Change in HbA1c between baseline and 6 months in each subgroup of participants.

Table 4 Adverse Events Recorded

Adverse Event	3 Months (n=114)	6 Months (n=120)
Total n (%)	36 (31.6)	20 (16.7)
Nausea	24 (21.1)	12 (10.0)
Vomiting	0 (0)	0 (0)
Abdominal pain	2 (1.8)	2 (1.7)
Dyspepsia	3 (2.6)	2 (1.7)
Diarrhea	1 (0.9)	0 (0)
Constipation	0 (0)	0 (0)
Hypoglycemia	3 (2.6)	1 (0.8)
Allergic reaction	1 (0.9)	2 (1.7)
Injection site reaction	1 (0.9)	1 (0.8)
Other	1 (0.9)	0 (0.0)

Note: Data are n (%).