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.
Highlights
International guidelines advise that if treatment with monotherapy does not result in optimal blood glucose levels dual therapy should be initiated (American Diabetes Association, 2014; Inzucchi et al, 2015; Canadian Agency for Drugs and Technologies in Health, 2013; Gunton et al, 2014; National Institute for Health and Clinical Excellence, 2011; New Zealand Guidelines Group, 2011)
NICE, Canada, Australia and New Zealand consider that MET and SU is the recommended dual therapy combination, unless contraindicated for the individual patient (American Diabetes Association, 2014; Inzucchi et al, 2015; Canadian Agency for Drugs and Technologies in Health, 2013; Gunton et al, 2014; National Institute for Health and Clinical Excellence, 2011; New Zealand Guidelines Group, 2011)
To test the hypothesis that all triple therapies were superior to dual therapy, we considered the minimal clinically important difference (MCID) to be −0.3% (3.3 mmol/mol) as used by the Federal Drug Agency (FDA) (CDER, 2008) and the European Medicines Association (CHMP, 2011) and quoted in Australia (Australian Government DoH, 2010)
Summary
International guidelines advise that if treatment with monotherapy does not result in optimal blood glucose levels dual therapy should be initiated (American Diabetes Association, 2014; Inzucchi et al, 2015; Canadian Agency for Drugs and Technologies in Health , 2013; Gunton et al, 2014; National Institute for Health and Clinical Excellence, 2011; New Zealand Guidelines Group, 2011). NICE, Canada, Australia and New Zealand consider that MET and SU is the recommended dual therapy combination, unless contraindicated for the individual patient (American Diabetes Association, 2014; Inzucchi et al, 2015; Canadian Agency for Drugs and Technologies in Health , 2013; Gunton et al, 2014; National Institute for Health and Clinical Excellence, 2011; New Zealand Guidelines Group, 2011). Given the number of medications available for type 2 diabetes; clinicians and patients need information about their effectiveness and safety to make informed choices
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