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Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis

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Karagiannis, T., Paschos, P., Paletas, K., Matthews, D. R., Tsapas, A.·2012·BMJ
DOI 10.1136/bmj.e1369
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Abstract

OBJECTIVE: To assess the efficacy and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors compared with metformin as monotherapy, or with other commonly used hypoglycaemic drugs combined with metformin, in adults with type 2 diabetes mellitus. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, the Cochrane Library, conference proceedings, trial registers, and drug manufacturers' websites. ELIGIBILITY CRITERIA: Randomised controlled trials of adults with type 2 diabetes mellitus that compared a DPP-4 with metformin as monotherapy or with a sulfonylurea, pioglitazone, a glucagon-like peptide-1 (GLP-1) agonist, or basal insulin combined with metformin on the change from baseline in glycated haemoglobin (HbA(1c)). DATA EXTRACTION: The primary outcome was the change in HbA(1c). Secondary outcomes included the proportion of patients achieving the goal of HbA(1c) <7%, the change in body weight, discontinuation rate because of any adverse event, occurrence of any serious adverse event, all cause mortality, and incidence of hypoglycaemia, nasopharyngitis, urinary tract infection, upper respiratory infection, nausea, vomiting, and diarrhoea. RESULTS: 27 reports of 19 studies including 7136 patients randomised to a DPP-4 inhibitor and 6745 patients randomised to another hypoglycaemic drug were eligible for the systematic review and meta-analysis. Overall risk of bias for the primary outcome was low in three reports, unclear in nine, and high in 14. Compared with metformin as monotherapy, DPP-4 inhibitors were associated with a smaller decline in HbA(1c) (weighted mean difference 0.20, 95% confidence interval 0.08 to 0.32) and in body weight (1.5, 0.9 to 2.11). As a second line treatment, DPP-4 inhibitors were inferior to GLP-1 agonists (0.49, 0.31 to 0.67) and similar to pioglitazone (0.09, -0.07 to 0.24) in reducing HbA(1c) and had no advantage over sulfonylureas in the attainment of the HbA(1c) goal (risk ratio in favour of sulfonylureas 1.06, 0.98 to 1.14). DPP-4 inhibitors had a favourable weight profile compared with sulfonylureas (weighted mean difference -1.92, -2.34 to -1.49) or pioglitazone (-2.96, -4.13 to -1.78), but not compared with GLP-1 agonists (1.56, 0.94 to 2.18). Only a minimal number of hypoglycaemias were observed in any treatment arm in trials comparing a DPP-4 inhibitor with metformin as monotherapy or with pioglitazone or a GLP-1 agonist as second line treatment. In most trials comparing a DPP-4 inhibitor with sulfonylureas combined with metformin, the risk for hypoglycaemia was higher in the group treated with a sulfonylurea. Incidence of any serious adverse event was lower with DPP-4 inhibitors than with pioglitazone. Incidence of nausea, diarrhoea, and vomiting was higher in patients receiving metformin or a GLP-1 agonist than in those receiving a DPP-4 inhibitor. Risk for nasopharyngitis, upper respiratory tract infection, or urinary tract infection did not differ between DPP-4 inhibitors and any of the active comparators. CONCLUSION: In patients with type 2 diabetes who do not achieve the glycaemic targets with metformin alone, DPP-4 inhibitors can lower HbA(1c), in a similar way to sulfonylureas or pioglitazone, with neutral effects on body weight. Increased unit cost, which largely exceeds that of the older drugs, and uncertainty about their long term safety, however, should also be considered.

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Authors
Karagiannis, T., Paschos, P., Paletas, K., Matthews, D. R., & Tsapas, A.
Affiliations
  • Aristotle University of Thessaloniki (GR)
  • University of Oxford (GB)
ORCID
Venue
BMJ
Publisher
BMJ
Published
2012-03-12
Volume
344
Issue
mar12 1
Pages
e1369-e1369
ISSN
  • 0007-1447 (ISSN-L)
  • 0959-8138
  • 1468-5833
DOI
10.1136/bmj.e1369
OpenAlex
W2067736115
Cited by
435
References
10
Citations by year
2026: 6 · 2025: 16 · 2024: 17 · 2023: 13 · 2022: 10 · 2021: 21 · 2020: 24 · 2019: 25 · 2018: 28 · 2017: 44 · 2016: 48 · 2015: 55 · 2014: 50 · 2013: 48 · 2012: 29
FWCI
8.13
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
National Institute for Health and Care Research (NF-SI-0508-10272)
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 › Pharmacology › Pharmacology and Obesity Treatment
Keywords
DPP-4 inhibitors, type 2 diabetes, metformin, HbA1c, body weight, hypoglycemia, adverse events, GLP-1 receptor agonists, pioglitazone, sulfonylureas, basal insulin, combination therapy, drug safety and efficacy, second-line therapy
MeSH terms
Adult, Blood Glucose, Body Weight, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Male, Metformin, Sulfonylurea Compounds, Randomized Controlled Trials as Topic, Treatment Outcome, Drug Monitoring, Outcome Assessment, Health Care, Disease Management, Glucagon-Like Peptide 1, Dipeptidyl-Peptidase IV Inhibitors

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