Triple therapy in type 2 diabetes; a systematic review and network meta-analysis - PubMed (original) (raw)

Triple therapy in type 2 diabetes; a systematic review and network meta-analysis

Martin J Downes et al. PeerJ. 2015.

Abstract

Aims. The purpose was to evaluate the evidence for triple therapy regimen using medicines available in Australia for type 2 diabetes. Methods. A systematic literature review was performed to update the relevant evidence from 2002 to 2014 on triple therapy for type 2 diabetes. A multiple-treatments network meta-analysis was undertaken to summarise the comparative efficacy and harms of different triple therapies. Results. Twenty seven trials were identified, most were six months of duration. The following combinations were included in the network meta-analysis: metformin (MET) + sulfonylureas (SU) (used as reference combination); MET + SU+ dipeptidyl peptidase 4 inhibitors (DPP-4-i); MET + SU+ thiazolidinediones (TZD); MET + SU+ glucagon-like peptide-1 receptor agonists (GLP-1-RA); MET + SU+ insulins; MET + TZD + DPP-4-i; and MET + SU+ sodium/glucose cotransporter 2 inhibitors (SGLT2-i). For HbA1c reduction, all triple therapies were statistically superior to MET+SU dual therapy, except for MET + TZD + DPP-4-i. None of the triple therapy combinations demonstrated differences in HbA1c compared with other triple therapies. MET + SU + SGLT2-i and MET + SU + GLP-1-RA resulted in significantly lower body weight than MET + SU + DPP-4-i, MET+SU+insulin and MET + SU + TZDs; MET + SU + DPP-4-i resulted in significantly lower body weight than MET + SU + insulin and MET + SU + TZD. MET + SU + insulin, MET + SU + TZD and MET + SU + DPP-4-i increased the odds of hypoglycaemia when compared to MET + SU. MET + SU + GLP-1-RA reduced the odds of hypoglycaemia compared to MET + SU + insulin. Conclusion. Care when choosing a triple therapy combination is needed as there is often a risk of increased hypoglycaemia events associated with this regimen and there are very limited data surrounding the long-term effectiveness and safety of combined therapies.

Keywords: Anti-diabetic medication; Glycated haemoglobin; Network meta-analysis; Oral antidiabetic drugs; Type 2 diabetes.

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Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1

Figure 1. PRISMA flow diagram for RCTs in a systematic review of triple therapy in type 2 diabetes.

Flow diagram showing the total number of records identified and the number of records filtered at each stage of the selection process from the systematic search for randomised control trials of type 2 diabetes in November 2014.

Figure 2

Figure 2. Line plots for different in efficacy and safety outcomes of triple therapy combinations compared to MET + SU dual therapy in type 2 diabetes.

Line (forest) plots of mean difference of change in HbA1c (A), change in body weight (B), and hypoglycaemia (C), for different triple therapy combinations compared to MET + SU dual therapy. Abbreviations: CI, confidence interval; MD, mean difference; DPP-4-i, dipeptidyl peptidase-4 inhibitor; GLP-1-RA, glucagon-like peptide-1 receptor agonist; NGSP, National Glycohemoglobin Standardization Program; IFCC, International Federation of Clinical Chemistry and Laboratory Medicine. HbA1c, glycated haemoglobin; INS, insulin; MET, metformin; PBO, placebo; SU, sulfonylurea; TZD, thiazolidinedione; sodium/glucose cotransporter 2 inhibitors (SGLT2-i).

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