Efficacy and safety of the addition of a dipeptidyl peptidase-4 inhibitor to insulin therapy in patients with type 2 diabetes: A systematic review and meta-analysis.
OBJECTIVE
To compare the efficacy and safety of the addition of a dipeptidyl peptidase-4 (DPP-4) inhibitor or a placebo in patients with type 2 diabetes inadequately controlled with insulin.


METHODS
We searched randomised controlled trials (RCTs) from MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials and the ClinicalTrials.gov online registry. Studies of at least 12week treatment duration were eligible if they were RCTs in patients with type 2 diabetes comparing addition of a DPP-4 inhibitor to insulin therapy (INS/DPP4i) with addition of a placebo to insulin therapy (INS/PCB) and contained information on the change in glycated haemoglobin (HbA1c) from baseline.


RESULTS
Of 3105 potentially relevant published articles and 206 registered trials, 9 studies were included for meta-analysis. Compared to INS/PCB, INS/DPP4i exhibited a greater reduction in HbA1c (weighted mean difference [WMD] -0.58%; 95% CI -0.70, -0.46) and fasting plasma glucose (WMD -0.59mmol/L; 95% CI -0.79, -0.40) with less daily insulin doses (WMD -1.86IU; 95% CI -3.27, -0.45) and with no difference in weight gain (WMD -0.04kg; 95% CI -0.25, 0.16). The risk of hypoglycaemia was similar between INS/DPP-4i and INS/PCB (the RR in favour of INS/PCB was 0.94; 95% CI 0.84, 1.05).


CONCLUSIONS
Compared to placebo, DPP-4 inhibitors exhibit a better glycaemic control without further increasing the risk of weight gain and hypoglycaemia in patients with type 2 diabetes inadequately controlled with insulin.
Division of Endocrinology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
Yeong Gi
YG
Kim
Division of Endocrinology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Se Hee
SH
Min
Department of Medicine, Seoul National University College of Medicine/Biostatistics Division of Medical Research Collaborating Center, Seoul National University Hospital, Seoul, South Korea.
Seokyung
S
Hahn
Division of Endocrinology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Tae Jung
TJ
Oh
Division of Endocrinology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Kyong Soo
KS
Park
Division of Endocrinology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: ymchomd@snu.ac.kr.
Young Min
YM
Cho
D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin
Dipeptidyl peptidase-4 inhibitor; Insulin; Meta-analysis; Systematic review; Type 2 diabetes