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

Paraskevi Liakopoulou, Aris Liakos, Despoina Vasilakou, Eleni Athanasiadou, Eleni Bekiari, Kyriakos Kazakos, Apostolos Tsapas

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. 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. 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). 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.