Meta‐analysis of head‐to‐head clinical trials comparing incretin‐based glucose‐lowering medications and basal insulin: An update including recently developed glucagon‐like peptide‐1 (GLP‐1) receptor agonists and the glucose‐dependent insulinotropic polypeptide/GLP‐1 receptor co‐agonist tirzepatide

• Published in: Diabetes, obesity & metabolism Vol. 25; no. 5; pp. 1361 - 1371
• Main Authors: Nauck, Michael A., Mirna, Abd El Aziz, Quast, Daniel R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2023; Wiley Subscription Services, Inc
• Subjects: Agonists; Antidiabetics; basal insulin; Blood Glucose; Blood pressure; Body Weight; Clinical trials; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Diarrhea; fasting plasma glucose; Gastric Inhibitory Polypeptide; GIP/GLP‐1 receptor co‐agonists; GLP‐1 receptor agonists; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor - agonists; Glucose; glycaemic control; HbA1c; Hemoglobin; Humans; Hypoglycemia; Hypoglycemia - chemically induced; Hypoglycemia - drug therapy; Hypoglycemia - prevention & control; Hypoglycemic Agents - therapeutic use; Incretins - therapeutic use; Insulin; Insulins; Lipids; Meta-analysis; Patients; Polypeptides; type 2 diabetes; Vomiting; body weight; basal insulin; type 2 diabetes; GLP-1 receptor agonists; GIP/GLP-1 receptor co-agonists; glycaemic control; fasting plasma glucose; HbA1c
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.14988

Objective To assess comparative efficacy, safety and tolerability of injectable incretin‐based glucose‐lowering medications (IBGLMs) versus basal insulin treatment in patients with type 2 diabetes. Research Design and Methods We performed an updated meta‐analysis of randomized clinical trials of head‐to‐head comparisons of IBGLMs (short‐ and long‐acting glucagon‐like peptide‐1 [GLP‐1] receptor agonists [GLP‐1RAs] and glucose‐dependent insulinotropic polypeptide [GIP]/GLP‐1 receptor co‐agonist tirzepatide) versus basal insulin using a PubMed database search (April 2022). The primary endpoint was difference in reduction of glycated haemoglobin (HbA1c) versus baseline between pooled IBGLMs (fixed‐effects meta‐analysis) and their subgroups (random‐effects meta‐analysis) versus basal insulin treatment (mean differences). Secondary endpoints were fasting plasma glucose, body weight, HbA1c target achievement, hypoglycaemia, blood pressure and lipids. Risk of bias assessment was performed using Jadad scores and the Risk of Bias tool 2.0. Results In all, 20 studies, representing 47 study arms and 11 843 patients, were eligible. Compared with basal insulin, IGBLMs lowered HbA1c by 0.48 (0.45‐0.52)% more than did basal insulin treatment. This effect was driven by pooled long‐acting GLP‐1RAs (ΔHbA1c −0.25 [−0.38; −0.11]%) and the only GIP/GLP‐1 receptor co‐agonist, tirzepatide (pooled doses; ΔHbA1c −0.90 [−1.06; −0.75]%), while short‐acting GLP‐1RAs were equally effective compared with basal insulin (P = 0.90). All IBGLM subgroups achieved significantly lower body weight versus insulin treatment (−4.6 [−4.7; −4.4] kg), in particular tirzepatide (−12.0 [−13.8; −10.1] kg). IBGLMs significantly reduced hypoglycaemia and blood pressure and improved lipid variables. Risk of bias was low. IBGLM treatment was associated with more nausea, vomiting and diarrhoea and study medication discontinuation. Conclusions Recently introduced, highly effective IBGLMs were superior to basal insulin treatment, reinforcing the recommendation that IBGLMs should be considered as the first injectable treatment for most patients with type 2 diabetes.