Insulin plus incretin: A glucose-lowering strategy for type 2-diabetes

Table 1 Published clinical trials with glucagon-like peptide-1 receptor agonists added to ongoing insulin therapy

		Exenatide BID	Lixisenatide
Ref		56	58	59	60
Number of patients		259	495	446	311
Duration (wk)		30	24	24	24
HbA1c	Baseline	8.3 ± 0.9	8.4 ± 0.9	7.6 ± 0.5	8.5 ± 0.7
	Change	-1.7 (-1.9, -1.6)	-0.7 ± 0.1	-0.7 ± 0.1	-0.8 ± 0.2
	Baseline comparator	8.5 ± 1.0	8.4 ± 0.8	7.6 ± 0.5	8.5 ± 0.8
	Change comparator	-1.0 (-1.2, -0.9)	-0.4 ± 0.1	-0.4 ± 0.1	+0.1 ± 0.2
FPG (mmol/L)	Baseline	7.9 ± 2.1	8.1 ± 2.8	6.6 ± 1.7	7.8 ± 2.2
	Change	-1.6 (-1.9, -1.3)	-0.6 ± 0.2	-0.3 ± 0.2	-0.4 ± 0.3
	Baseline comparator	8.3 ± 2.3	8.0 ± 2.7	6.7 ± 2.0	7.7 ± 2.3
	Change comparator	-1.5 (-1.8, -1.2)	-0.6 ± 0.3	-0.5 ± 0.2	0.3 ± 0.3
Hypoglycemia	GLP-1RA	1.41	2062	283	423; 334
	Comparator	1.21	5222	223	243; 284
Body weight	Baseline	95 ± 20	89 ± 21	88 ± 22	66 ± 13
	Change	-1.8 (-2.4, -1.1)	-1.8 ± 0.2	0.3 ± 0.3	-0.4
	Baseline comparator	93 ± 21	88 ± 20	87 ± 21	66 ± 12
	Change comparator	1.0 (0.2, 1.7)	-0.5 ± 0.3	1.2 ± 0.3	+0.1

Insulin glargine was used in all studies. Occurrence of hypoglycemia was reported as number of episodes per patient year¹, number of events² or as percentage of patients with at least one hypoglycemic episode³. One study also reported percentage of patients not on sulfonylurea who experienced at least one hypoglycemic episode⁴. Variation in baseline is SD, variation in effect is SE. Variation within parenthesis is the 95%CI. FPG: Fasting glucose; GLP-1: Glucagon-like peptide-1; HbA1c: Hemoglobin A1c.

Table 2 Published clinical trials with dipeptidyl peptidase-4 inhibitors combined with basal ± prandial insulin

		Vildagliptin		Sitagliptin		Alogliptin	Saxagliptin	Linagliptin
Ref		62	63	64	65	67	69	70
Number of patients		296	449	641	124	390	455	1261
Study duration (wk)		24	24	24	24	26	52	24
Comparator		Stable insulin	Stable insulin	Stable insulin	Increasing insulin	Stable insulin	Stable insulin	Stable insulin
HbA1c (%)	Baseline	8.4 ± 1.0	8.8 ± 1.0	8.7 ± 0.9	9.2 ± 1.0	9.3 ± 1.1	8.7 ± 0.9	8.3 ± 0.1
	Change	-0.5 ± 0.1	-0.8 ± 0.1	-0.6 (-0.7, -0.5)	-0.6 (-0.9, -0.3)	-0.7	-0.8 ± 0.1	-0.6 ± 0.1
	Baseline placebo	8.4 ± 1.1	8.8 ± 1.0	8.6 ± 0.9	9.2 ± 1.1	9.3 ± 1.1	8.6 ± 0.9	8.3 ± 0.1
	Change placebo	-0.2 ± 0.1	-0.1 ± 0.1	0 (-0.1, 0.1)	-0.2 (-0.5, 0.3)	-0.1	-0.4 ± 0.1	-0.1 ± 0.1
FPG (mmol/L)	Baseline	9.3 ± 3.1	9.6 ± 2.6	9.8 ± 2.9	9.0 ± 3.3	10.3 ± 3.9	NR	8.2 ± 2.6
	Change	-0.8 ± 0.3	-0.8	-1.0 (-1.4, -0.7)	-1.0 (-2.7, -0.2)	-0.6 ± 0.3		-0.2 ± 0.2
	Baseline placebo	8.7 ± 3.1	9.1 ± 2.5	9.9 ± 3.3	8.4 ± 2.8	10.9 ± 4.3	NR	8.4 ± 2.6
	Change placebo	-0.2 ± 0.4	-0.2	-0.2 (-0.6, 0.2)	-1.3 (-1.8, -0.5)	0.3 ± 0.3		-0.3 ± 0.2
Hypoglycemia		1131	8.42	162	72	202	232	232
Hypoglycemia placebo		1851	7.22	82	142	402	272	222
Body weight (kg)	Baseline	95 ± 2	78 ± 16	87 ± 19	69 ± 12	87 ± 19	88 ± 18	BMI (31 ± 5)
	Change	1.3 ± 0.3	0.1	-0.1 (-0.2, 0.4)	-0.7 (-1.4, -0.1)	0.6 ± 0.2	0.8	-0.2 ± 0.1
	Baseline placebo	95 ± 2	79 ± 17	87 ± 18	66 ± 10	91 ± 21	86 ± 16	BMI (31 ± 5)
	Change placebo	0.6 ± 0.3	-0.4	-0.1 (-0.3, 0.4)	1.1 (0.2, 1.8)	0.6 ± 0.2	0.5	0.1 ± 0.1

In the studies long and medium acting insulin and premixed insulins were used. Occurrence of hypoglycemia was reported as number of events¹ or as percentage of patients with at least one hypoglycemic episode². Variation in baseline is SD, variation in effect is SE. Variation within parenthesis is the 95%CI. FPG: Fasting glucose; BMI: Body mass index (kg/m²); HbA1c: Hemoglobin A1c.