The effect of subcutaneous dulaglutide on weight loss in patients with Type 2 diabetes mellitus: Systematic review and meta-analysis of randomized controlled trials

Background: Dulaglutide, a subcutaneously administered glucagon-like peptide 1 receptor agonist, has been hypothesized to lead to weight loss in patients with Type 2 diabetes mellitus (T2DM). However, the consequences of its prescription on body weight (BW) and other anthropometric indices, for example, body mass index (BMI) or waist circumference (WC), have not been completely clarified. Therefore, we aimed to assess the effects of subcutaneous dulaglutide administration on BW, BMI and WC values in T2DM subjects by means of a systematic review and meta-analysis of RCTs.Methods: We computed a literature search in five databases (PubMed/Medline, Web of Science, EMBASE, Scopus and Google Scholar) from their inception to February 2023 to identify RCTs that examined the influence of subcutaneous dulaglutide on obesity indices. We calculated effect sizes using the random-effects model (using DerSimonian-Laird method). Results were derived across weighted mean differences (WMD) and 95% confidence intervals (CI). Subgroup analyses were applied to explore possible sources of heterogeneity among the RCTs. The current systematic review and meta-analysis was conducted in compliance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Results: In total, 18 studies with 33 RCT arms (BW = 33 RCT arms, 14,612 participants, 7869 cases and 6743 controls; BMI = 10 RCT arms, 14,612 subjects, 7869 cases and 6743 controls; WC = 10 RCT arms, 1632 participants, 945 cases and 687 cases) were included in the meta-analysis. BW (WMD: -0.86 kg, 95% CI: -1.22, -0.49, p < 0.001), BMI (WMD: -0.68 kg/m(2), 95% CI: -0.88, -0.49, p < 0.001) and WC (WMD: -1.23 cm, 95% CI: -1.82, -0.63, p < 0.001) values decreased notably following subcutaneous dulaglutide administration versus placebo. BW notably decreased in RCTs lasting >18 weeks (WMD: -1.42 kg, 95% CI: -1.90, -0.94, p < 0.001), whereas notable reductions in WC were seen in RCTs lasting <= 18 weeks (WMD: -1.78 cm, 95% CI: -2.59, -0.98, p < 0.001). Dulaglutide dosages >1 mg/day significantly decreased BW (WMD: -1.94 kg, 95% CI: -2.54, -1.34, p < 0.001), BMI (WMD: -0.80 kg/m(2), 95% CI: -1.07, -0.54, p < 0.001) and WC (WMD: -1.47 cm, 95% CI: -1.80, -1.13, p < 0.001). BW decreased particularly following dulaglutide prescription in individuals with obesity (WMD: -1.05 kg, 95% CI: -1.28, -0.82, p < 0.001) versus overweight. The dose-response meta-analysis revealed that BW decreased significantly when dulaglutide was prescribed in doses <= 3 mg/day versus >3 mg/day.Conclusions: Subcutaneous dulaglutide administration in T2DM reduces BW, BMI and WC. The decrease in BW and WC was influenced by the dose and the duration of dulaglutide administration. The reduction in BMI was only influenced by the dosage of dulaglutide. Moreover, T2DM patients who suffered from obesity experienced a notable decrease in BW versus T2DM subjects without obesity.