Impact of dipeptidyl peptidase-4 inhibitors on glucose-dependent insulinotropic polypeptide in type 2 diabetes mellitus: a systematic review and meta-analysis

Shangyu Chai; Ruya Zhang; Richard David Carr; Carolyn F Deacon; Yiman Zheng; Swapnil Rajpathak; Jingya Chen; Miao Yu

doi:10.3389/fendo.2023.1203187

Impact of dipeptidyl peptidase-4 inhibitors on glucose-dependent insulinotropic polypeptide in type 2 diabetes mellitus: a systematic review and meta-analysis

Front Endocrinol (Lausanne). 2023 Aug 10:14:1203187. doi: 10.3389/fendo.2023.1203187. eCollection 2023.

Authors

Shangyu Chai¹, Ruya Zhang¹, Richard David Carr^{2

3}, Carolyn F Deacon^{3

4}, Yiman Zheng¹, Swapnil Rajpathak⁵, Jingya Chen¹, Miao Yu⁶

Affiliations

¹ Merck Research Laboratories (MRL) Global Medical Affairs, Merck Sharp & Dohme (MSD) China, Shanghai, China.
² Hatter Cardiovascular Institute, University College London, London, United Kingdom.
³ School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom.
⁴ Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁵ Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ, United States.
⁶ Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Abstract

Aims: Glucose-dependent insulinotropic polypeptide (GIP) confers a variety of metabolic benefits in type 2 diabetes mellitus (T2DM). This meta-analysis was conducted to investigate the impact of dipeptidyl peptidase 4 (DPP4) inhibitors on GIP levels in T2DM patients.

Methods: Medline (PubMed), CENTER (Cochrane Library), and Embase (Ovid) were searched and randomized controlled trials (RCTs) evaluating the impact of DPP4 inhibitors on fasting and postprandial GIP levels were obtained. For postprandial GIP, only studies with the data of GIP changes reported as the total area under the curve (AUC_GIP) using a meal or oral glucose tolerance test were included. A random-effects model was used for data pooling after incorporating heterogeneity.

Results: Overall, 14 RCTs with 541 T2DM patients were included. Compared to placebo/no treatment, the use of DPP4 inhibitors significantly increased the fasting GIP level (standard mean difference [SMD]: 0.77, 95% confidence interval [CI]: 0.48-1.05, P<0.001; I^{2 =}52%) and postprandial AUC_GIP (SMD: 1.33, 95% CI: 1.02-1.64, P<0.001; I^{2 =}65%). Influence analysis by excluding one dataset at a time showed consistent results. Sensitivity analyses only including studies with radioimmunoassay showed also consistent results (fasting GIP: SMD: 0.75, 95% CI: 0.51-1.00, P<0.001; I^{2 =}0%; and postprandial AUC_GIP: SMD: 1.48, 95% CI: 1.18-1.78, P<0.001; I^{2 =}54%). Further subgroup analyses demonstrated that the influence of DPP4 inhibitors on fasting and postprandial GIP levels in T2DM patients was not significantly changed by study characteristics such as study design, patient mean age, baseline glycated hemoglobin (HbA1c) concentration, body mass index (BMI), background treatment, treatment duration, or method for postprandial GIP measurement (all P for subgroup effects <0.05).

Conclusion: The use of DPP4 inhibitors effectively increases the fasting and postprandial GIP concentrations in T2DM patients.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022356716.

Keywords: dipeptidyl peptidase-4 inhibitor; glucose-dependent insulinotropic polypeptide; meta-analysis; metabolism; randomized controlled trials.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Diabetes Mellitus, Type 2* / drug therapy
Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
Gastric Inhibitory Polypeptide
Glucose
Humans

Substances

Dipeptidyl-Peptidase IV Inhibitors
Gastric Inhibitory Polypeptide
Glucose