Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis
Summary
Background
Combination
treatment with a glucagon-like peptide-1 (GLP-1) agonist and basal
insulin has been proposed as a treatment strategy for type 2 diabetes
that could provide robust glucose-lowering capability with low risk of
hypoglycaemia or weight gain. We thus did a systematic review and
meta-analysis of randomised controlled trials to assess the effect of
this combination treatment on glycaemic control, hypoglycaemia, and
weight gain in patients with type 2 diabetes.
Methods
We systematically searched PubMed, Embase, Cochrane, Web of Knowledge, FDA.gov, and ClinicalTrials.gov
for randomised controlled trials (published between Jan 1, 1950, and
July 29, 2014; no language restrictions) comparing GLP-1 agonist and
basal insulin combination treatment to other anti-diabetic treatments.
Our main endpoints were glycaemic control, hypoglycaemia, and change in
weight. We assessed pooled data by use of a random-effects model.
Findings
Of
2905 identified studies, 15 were eligible and were included in our
analysis (N=4348 participants). Compared with other anti-diabetic
treatments, GLP-1 agonist and basal insulin combination treatment
yielded an improved mean reduction in glycated haemoglobin (HbA1c) of −0·44% (95% CI −0·60 to −0·29), an improved likelihood of achieving the target HbA1c
of 7·0% or lower (relative risk [RR] 1·92; 95% CI 1·43 to 2·56), no
increased relative risk of hypoglycaemia (0·99; 0·76 to 1·29), and a
mean reduction in weight of −3·22 kg (−4·90 to −1·54). Furthermore,
compared with basal-bolus insulin regimens, the combination treatment
yielded a mean reduction in HbA1c of
−0·1% (−0·17 to −0·02), with lower relative risk of hypoglycaemia (0·67,
0·56 to 0·80), and reduction in mean weight (−5·66 kg; −9·8 to −1·51).
Interpretation
GLP-1
agonist and basal insulin combination treatment can enable achievement
of the ideal trifecta in diabetic treatment: robust glycaemic control
with no increased hypoglycaemia or weight gain. This combination is thus
a potential therapeutic strategy that could improve the management of
patients with type 2 diabetes.
a Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada
b Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
c Division of Endocrinology, University of Toronto, Toronto, ON, Canada
Correspondence to: Dr Ravi Retnakaran, Leadership Sinai Centre for
Diabetes, Mount Sinai Hospital, 60 Murray Street, Suite L5-025,
Mailbox-21, Toronto, ON M5T 3L9, Canada
† Joint first authors
