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Comparative Study
. 2014 Dec 23;4(12):e005752.
doi: 10.1136/bmjopen-2014-005752.

Safety and effectiveness of dipeptidyl peptidase-4 inhibitors versus intermediate-acting insulin or placebo for patients with type 2 diabetes failing two oral antihyperglycaemic agents: a systematic review and network meta-analysis

Andrea C Tricco  1 , Jesmin Antony  1 , Paul A Khan  1 , Marco Ghassemi  1 , Jemila S Hamid  2 , Huda Ashoor  1 , Erik Blondal  1 , Charlene Soobiah  1 , Catherine H Yu  1 , Brian Hutton  3 , Brenda R Hemmelgarn  4 , David Moher  3 , Sumit R Majumdar  5 , Sharon E Straus  6
Affiliations
Comparative Study

Safety and effectiveness of dipeptidyl peptidase-4 inhibitors versus intermediate-acting insulin or placebo for patients with type 2 diabetes failing two oral antihyperglycaemic agents: a systematic review and network meta-analysis

Andrea C Tricco et al. BMJ Open. .

Abstract

Objective: To evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM) and poor glycaemic control despite treatment with two oral agents.

Setting: Studies were multicentre and multinational.

Participants: Ten studies including 2967 patients with T2DM.

Interventions: Studies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM.

Primary and secondary outcome measures: Primary outcome was glycosylated haemoglobin (HbA1c). Secondary outcomes were healthcare utilisation, body weight, fractures, quality of life, microvascular complications, macrovascular complications, all-cause mortality, harms, cost and cost-effectiveness.

Results: 10 randomised clinical trials with 2967 patients were included after screening 5831 titles and abstracts, and 180 full-text articles. DPP-4 inhibitors significantly reduced HbA1c versus placebo in network meta-analysis (NMA; mean difference (MD) -0.62%, 95% CI -0.93% to -0.33%) and meta-analysis (MD -0.61%, 95% CI -0.81% to -0.41%), respectively. Significant differences in HbA1c were not observed for neutral protamine Hagedorn (NPH) insulin versus placebo and DPP-4 inhibitors versus NPH insulin in NMA. In meta-analysis, no significant differences were observed between DPP-4 inhibitors and placebo for severe hypoglycaemia, weight gain, cardiovascular disease, overall harms, treatment-related harms and mortality, although patients receiving DPP-4 inhibitors experienced less infections (relative risk 0.72, 95% CI 0.57 to 0.91).

Conclusions: DPP-4 inhibitors were superior to placebo in reducing HbA1c levels in adults with T2DM taking at least two oral agents. Compared with placebo, no safety signals were detected with DPP-4 inhibitors and there was a reduced risk of infection. There was no significant difference in HbA1c observed between NPH and placebo or NPH and DPP-4 inhibitors.

Trial registration number: PROSPERO # CRD42013003624.

Keywords: meta-analysis; systematic review.

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Figures

Figure 1
Figure 1
Study flow. This is the flow of studies for the systematic review. HbA1c, glycosylated haemoglobin; DPP-4, dipeptidyl peptidase-4 inhibitors.
Figure 2
Figure 2
Glycosylated haemoglobin network meta-analysis results. This is the forest plot for the glycosylated haemoglobin network meta-analysis. Crl, credit limit; DPP-4, dipeptidyl peptidase-4 inhibitors; NPH, neutral protamine Hagedorn; MD, mean difference.
Figure 3
Figure 3
Harms meta-analysis results. This is the forest plot for all harms meta-analyses. a, Unpublished data. N, sample size.
See this image and copyright information in PMC

References

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