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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

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.

References

    1. Canadian Diabetes Association. Clinical practice guidelines for the prevention and management of diabetes in Canada. Toronto, ON: Canadian Diabetes Association, 2008.
    1. Nathan DM, Buse JB, Davidson MB et al. . Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193–203. 10.2337/dc08-9025 - DOI - PMC - PubMed
    1. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–53. 10.1016/S0140-6736(98)07019-6 - DOI - PubMed
    1. Cook MN, Girman CJ, Stein PP et al. . Glycemic control continues to deteriorate after sulfonylureas are added to metformin among patients with type 2 diabetes. Diabetes Care 2005;28:995–1000. 10.2337/diacare.28.5.995 - DOI - PubMed
    1. Moher D, Shamseer L, Clarke M, et al. Reporting guidelines for systematic review protocols. 19th Cochrane Colloquium October 19–22. Madrid, Spain: Iberoamerican Cochrane Centre and Network, 2011.

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