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Efficacy and safety of initial combination therapy in treatment-naïve type 2 diabetes patients: a systematic review and meta-analysis

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Cai, Xiaoling, Gao, Xueying, Yang, Wenjia, Han, Xueyao, Ji, Linong·2018·Diabetes Therapy
DOI 10.1007/s13300-018-0493-2PMC PMC6167297
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Abstract

INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of initial combination therapy compared with monotherapy in drug-naïve type 2 diabetes patients. METHODS: MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched for randomized clinical trials of initial combination therapy with hypoglycemic agents compared with monotherapy. Those which satisfied the search criteria were included in the meta-analysis. Weighted mean difference and relative risks were calculated. RESULTS: A total of 36 studies were included in the meta-analysis. Compared with metformin monotherapy, initial combination therapy with metformin plus another anti-diabetes drug exhibited significant reductions in glycated hemoglobin (HbA1c) (p < 0.001). Most of the combination therapies had a similar risk of hypoglycemia (p > 0.05), with the exception of combinations of sulfonylurea/glinide and metformin or combinations of thiazolidinedione and metformin. Compared with dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy, initial combination therapy with DPP-4 inhibitor plus another anti-diabetes drug showed a significant decrease in HbA1c (p < 0.001) and a similar risk of hypoglycemia (p > 0.05). Compared with monotherapy with other anti-diabetes drugs, initial combination therapies also resulted in significant HbA1c reductions, a similar risk of hypoglycemia and similar risks of other adverse events. CONCLUSION: Compared with monotherapy, all initial combination therapies resulted in significant HbA1c reductions. Compared with metformin monotherapy, initial combination therapies with DPP-4 inhibitors plus metformin, sodium/glucose cotransporter 2 inhibitors and metformin, respectively, were associated with similar risks of hypoglycemia, but initial combination therapies with sulfonylurea plus metformin, thiazolidinedione and metformin, respectively, were associated with higher risks of hypoglycemia. FUNDING: AstraZeneca Ltd. (China). TRIAL REGISTRATION: Registration number CRD42017060717 in PROSPERO.

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Authors
Cai, X., Gao, X., Yang, W., Han, X., & Ji, L.
Affiliations
Peking University People's Hospital (CN)
Corresponding author
Ji, Linong
ORCID
Venue
Diabetes Therapy
Publisher
Springer Science and Business Media LLC
Published
2018-08-28
Volume
9
Issue
5
Pages
1995-2014
ISSN
  • 1869-6953 (ISSN-L)
  • 1869-6961
DOI
10.1007/s13300-018-0493-2
PMC
PMC6167297
OpenAlex
W2889345352
Cited by
47
References
3
Citations by year
2026: 4 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 10 · 2019: 4 · 2017: 1
FWCI
0.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Therapy (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • AstraZeneca Ltd. (meta-analysis)
  • Foundation for the Author of National Excellent Doctoral Dissertation of the People's Republic of China (2016YFC1304901)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
type 2 diabetes, monotherapy, metformin, DPP-4 inhibitors, sulfonylureas, thiazolidinediones, SGLT2 inhibitors, HbA1c, hypoglycemia, adverse events, treatment-naive patients

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