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Triple therapy combinations for the treatment of type 2 diabetes - A network meta-analysis
Crystal Man Ying Lee1, Mark Woodward2, Stephen Colagiuri1
1The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, Level 2 Charles Perkins Centre D17, University of Sydney, NSW 2006, Australia.
Aim:
To estimate and compare the results from all randomised trials of triple combinations of anti-diabetes therapies that reported the reduction of glycated haemoglobin (HbA1c) and associated effects on body weight and hypoglycaemia.
Methods:
PubMed and the Cochrane Library were searched for trials with at least one study arm on triple therapy and which reported the differences in mean change in HbA1c between two study arms. These were included in a network meta-analysis.
Results:
Altogether, 15,182 participants from 40 trials with treatment duration of 6-12months were included. Compared with none/placebo added to dual therapy, the addition of a drug therapy from six of eight drug classes to existing dual therapy resulted in significant additional mean reductions in HbA1c from -0.56% (-6.2mmol/mol; dipeptidyl peptidase 4 inhibitors) to -0.94% (-10.3mmol/mol; thiazolidinediones). Of the six drug classes, three were associated with less favourable weight change and two were associated with more favourable weight change when compared with none/placebo added to dual therapy. Furthermore, five drug classes were associated with greater odds of hypoglycaemia. Similar results were observed in analyses of studies with a 6month treatment duration and after excluding study arms that contained insulin.
Conclusions:
Overall triple therapy combinations were similar in improving diabetes control although there were some differences in adverse effects. By balancing the risks and benefits of each therapy, the estimates of pairwise comparisons of triple therapies for HbA1c, body weight and hypoglycaemia provided in this study may further inform evidence based practice.
Insights
Triple therapy combinations for type 2 diabetes show similar improvements in glycated hemoglobin (HbA1c) control. However, differences exist in associated effects on body weight and risk of hypoglycemia, impacting evidence-based practice.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Pharmacology
Background:
- Type 2 diabetes management often requires combination therapy.
- Triple therapy, adding a third agent to dual therapy, is increasingly used.
- Understanding the comparative efficacy and safety of triple therapy combinations is crucial.
Purpose of the Study:
- To conduct a network meta-analysis of randomized trials on triple anti-diabetes therapies.
- To compare the reduction in glycated hemoglobin (HbA1c) achieved by different triple therapy combinations.
- To evaluate associated effects on body weight and the risk of hypoglycemia.
Main Methods:
- Systematic search of PubMed and Cochrane Library for relevant randomized trials.
- Inclusion of trials reporting mean change in HbA1c between study arms.
- Network meta-analysis to compare multiple triple therapy combinations.
Main Results:
- 40 trials with 15,182 participants were included (6-12 months duration).
- Six of eight drug classes added to dual therapy significantly reduced HbA1c compared to placebo.
- Adverse effects varied, with some drug classes linked to unfavorable weight changes or increased hypoglycemia risk.
Conclusions:
- Triple therapy combinations offer comparable improvements in diabetes control (HbA1c).
- Significant differences in adverse effects (body weight, hypoglycemia) exist among drug classes.
- Balancing risks and benefits is essential for informed clinical decision-making in diabetes management.
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