The good companions: insulin and glucagon-like peptide-1 receptor agonist in type 2 diabetes. A systematic review and meta-analysis of randomized controlled trials

Diabetes Res Clin Pract. 2019 Aug;154:101-115. doi: 10.1016/j.diabres.2019.06.009. Epub 2019 Jun 22.


We provided an updated systematic review with meta-analysis of randomized controlled trials (RCTs) assessing the metabolic effects of combination therapy of insulin and GLP-1RA (combo) in comparison with other injectable therapy. We searched PubMed, Cochrane Register of Controlled Trials, Scholar, and for RCTs evaluating changes in HbA1c (primary outcome), proportion of patients at HbA1c target <7%, hypoglycaemia, and weight change (secondary end-points). We included 36 RCTs involving 14,636 patients. Compared with comparator therapies (overall analysis), the combo led to a significant HbA1c reduction (=-0.49%, 95% CI -0.61 to -0.38%, P < 0.001), more patients at HbA1c target [relative risk, (RR) = 1.77, 95% CI, 1.56, 2.01, P < 0.001], similar hypoglycaemic events (RR = 1.03, 95% CI, 0.88, 1.19, P = 0.728), and reduction in body weight (-2.5 Kg, 95% CI -3.1 to -1.8 kg, P < 0.001), with high heterogeneity in each analysis. The quality of the evidence was low for three of the considered outcomes. Compared with intensified insulin regimens (basal-plus/basal-bolus) the combo produced similar glycemic control with reduction of both hypoglycaemia, and body weight. Combination therapy of GLP-1RA and insulin could represent a valuable treatment strategy to improve glycemic control in the management of type 2 diabetes.

Keywords: Basal insulin; Combination therapy; GLP-1 RAs; Glycemic control; Meta-analysis; Randomized controlled trials; Type 2 diabetes.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Humans
  • Hypoglycemia / prevention & control*
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Prognosis
  • Randomized Controlled Trials as Topic


  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Insulin