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Fixed ratio combinations of glucagon like peptide 1 receptor agonists with basal insulin: a systematic review and meta-analysis

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Abstract

Purpose

Basal insulin controls primarily fasting plasma glucose but causes hypoglycaemia and weight gain, whilst glucagon like peptide 1 receptor agonists induce weight loss without increasing risk for hypoglycaemia. We conducted a systematic review and meta-analysis of randomised controlled trials to investigate the efficacy and safety of fixed ratio combinations of basal insulin with glucagon like peptide 1 receptor agonists.

Methods

We searched Medline, Embase, and the Cochrane Library as well as conference abstracts up to December 2016. We assessed change in haemoglobin A1c, body weight, and incidence of hypoglycaemia and gastrointestinal adverse events.

Results

We included eight studies with 5732 participants in the systematic review. Switch from basal insulin to fixed ratio combinations with a glucagon like peptide 1 receptor agonist was associated with 0.72% reduction in haemoglobin A1c [95% confidence interval –1.03 to –0.41; I 2 = 93%] and 2.35 kg reduction in body weight (95% confidence interval –3.52 to –1.19; I 2 = 93%), reducing also risk for hypoglycaemia [odds ratio 0.70; 95% confidence interval 0.57 to 0.86; I 2 = 85%] but increasing incidence of nausea (odds ratio 6.89; 95% confidence interval 3.73–12.74; I 2 = 79%). Similarly, switching patients from treatment with a glucagon like peptide 1 receptor agonist to a fixed ratio combination with basal insulin was associated with 0.94% reduction in haemoglobin A1c (95% confidence interval –1.11 to –0.77) and an increase in body weight by 2.89 kg (95% confidence interval 2.17–3.61).

Conclusions

Fixed ratio combinations of basal insulin with glucagon like peptide 1 receptor agonists improve glycaemic control whilst balancing out risk for hypoglycaemia and gastrointestinal side effects.

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Authors and Affiliations

  1. Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece

    Paraskevi Liakopoulou, Aris Liakos, Eleni Athanasiadou, Eleni Bekiari & Apostolos Tsapas

  2. Third Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece

    Despoina Vasilakou

  3. Alexander Technological Educational Institute of Thessaloniki, Thessaloniki, Greece

    Kyriakos Kazakos

  4. Harris Manchester College, University of Oxford, Oxford, UK

    Apostolos Tsapas

Authors
  1. Paraskevi Liakopoulou
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  2. Aris Liakos
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  4. Eleni Athanasiadou
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Correspondence to Apostolos Tsapas.

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Conflict of interest

P.L. was supported by a scholarship from Novo Nordisk for the completion of a Master’s degree in Diabetes Mellitus Care. A.L. has received travelling fees from Novo Nordisk. K. K. has received advisory board consulting fees or honoraria from Novo Nordisk, Astra Zeneca, and has lectured for Novo Nordisk, Sanofi, Boehringer Ingelheim, Astra Zeneca and Pharmaserve—Lilly. A.T. has received ad hoc clinical research support and speaker’s honoraria from Novo Nordisk and Sanofi. The remaining authors declare that they have no competing interests.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Liakopoulou, P., Liakos, A., Vasilakou, D. et al. Fixed ratio combinations of glucagon like peptide 1 receptor agonists with basal insulin: a systematic review and meta-analysis. Endocrine 56, 485–494 (2017). https://doi.org/10.1007/s12020-017-1293-6

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