DPP-4 Inhibitors as Treatments for Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Table 1

Characteristics of the included studies.

Studies	Hari et al. (NCT01235819)	Griffin et al. (NCT01155284)	Garg et al. (NCT01227460)	Zhao et al. (NCT01159847)	Farngren et al. (NCT01147276)
Experimental treatment	Sitagliptin (100 mg, qd) + insulin^a (premix insulin)	Sitagliptin (100/50 mg, qd) + lansoprazole (60/30 mg, qd) + insulin (unspecified)	Sitagliptin (100 mg, qd) + insulin^b (premixed insulin excluded)	Sitagliptin (100 mg, qd) + insulin (unspecified)	Vildagliptin (50 mg, bid) + insulin^c (long-acting and short-acting insulin)
Control treatment^d	Insulin (bid-tid)	Placebo + insulin	Placebo + insulin	Insulin	Placebo + insulin
Treatment period (weeks)	52	52	16	52	8
Experimental samples	6	40	63	15	14
Control samples	6	18	62	15	14
Average age (years)	27.15 ± 4.20	16.18 ± 5.78	37.99 ± 14.01	47.45 ± 3.27	U
Mean duration of T1DM	33.25 ± 9.37 d	103.41 ± 51.74 d	21.01 ± 11.00 y	1.4 ± 0.20 y	11.0 ± 4.30 y
Average BMI (kg/m^2)	21.50 ± 3.39	21.51 ± 3.95	27.45 ± 4.54	23.35 ± 0.85	24.8 ± 3.30
Design	RCT	RCT	RCT	RCT	RCT
Number of centers	1	3	3	1	1
HbA1c at baseline (%)	9.75 ± 0.83	7.18 ± 1.09	8.55 ± 0.70	6.45 ± 0.20	7.49 ± 0.55
Cholesterol at baseline (mmol/L)	U	U	U	4.65 ± 0.16	U
C-peptide at baseline (pmol/L)	0.395 ± 0.15^e	685.44 ± 412.36	≥16 pmol/L^f	401.75 ± 52.27^g	U
LDL-C at baseline (mmol/L)	U	U	U	2.75 ± 0.13	U
Triglyceride at baseline (mmol/L)	U	U	U	1.2 ± 0.1	U
Inclusion criteria	Recent T1DM < 3 m, GAD^+or stimulated CP < 0.5 ng/mL, age < 30 y	Aged 11–36 y, <6 m	Aged 18–80 y, after diagnosed for 1 y, BMI < 35 kg/m^2	Aged 25–70 y, FCP ≥ 200/2 hCP ≥ 400 pmol/L, duration < 3 y, LADA	Age > 18 y, duration of 2–20 y, HbA1c of 6.5–8.5%
Exclusion criteria	C-peptide < 0.1 ng/mL, age > 30 y, pancreatic disease	Risk of pancreatitis, pregnant	BMI ≥ 35 kg/m^2	Other autoimmune diseases, insulin > 0.8 U/kg/d, renal disease	Pregnant or lactating, acute infection, liver disease, blood donor, using GH or oral steroid

d: days; m: months; y: years. Data are presented as the mean ± SD or as numbers (percentages). U: unknown; NG: not given; GH: growth hormone; BMI: body mass index; RCT: randomized controlled trial. ^aPatients initially were started on a twice daily premixed insulin regime (25% insulin Lispro and 75% insulin Lispro protamine) and later shifted to a three-times-daily premixed regime depending on their glycemic profiles. ^bPatients may be using insulin via a continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) containing bolus and basal insulin. ^cTwenty-six patients were treated with daily basal-bolus injections; their mean insulin dose was 30 U/d (long-acting insulin; 0.37 ± 0.07 U/kg) and 31 U/d (short-acting insulin; 0.37 ± 0.09 U/kg). Two patients were treated with a continuous sc insulin infusion [daily dose 60 and 36 U (0.67 and 0.52 U/kg), resp.]. ^dThe insulin dosages used were consistent with the experimental group. ^eng/mL; ^fonly 20 patients were reported to be C-peptide-positive; ^gfasting C-peptide level.