Awadhesh Kumar Singh1, Kalyan Kumar Gangopadhyay2, Ritu Singh3. 1. Department of Endocrinology, G.D Hospital & Diabetes Institute , Kolkata, India. 2. Department of Endocrinology, Fortis & Peerless Hospital , Kolkata, India. 3. Department of Gynecology & Obstetrics, G. D Hospital & Diabetes Institute , Kolkata, India.
Abstract
BACKGROUND: The link of acute pancreatitis (AP) with Incretin based therapies (IBTs) in type 2 diabetes has existed since United States Food and Drug Administration alert in 2010. This issue still remains unresolved due to conflicting results among studies. RESEARCH DESIGN AND METHODS: We performed a systematic search of the PubMed, Embase, and Cochrane Library databases until 31 July 2019, and retrieved all cardiovascular outcome trials (CVOTs) of IBTs conducted for ≥12 months that reported the pre-specified and or pre-adjudicated pancreatitis outcomes. Subsequently, we conducted a meta-analysis to study the risk of AP observed with IBT in CVOTs. RESULTS: A meta-analysis of seven CVOTs of GLP-1 receptor agonists (GLP-1RAs) compared with placebo (N = 55,932) found no significant increase in AP (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.77-1.42; p = 0.77). In contrast, meta-analysis of five CVOTs comparing DPP-4 inhibitors with placebo (N = 47,714) and six CVOTs comparing DPP-4 inhibitors with placebo or active comparator (N = 53,747), found a significant increase (OR, 1.81; 95% CI, 1.21-2.70; p = 0.04 and OR, 1.54; 95% CI, 1.08-2.18; p = 0.02, respectively) in AP without any significant heterogeneity. CONCLUSIONS: This meta-analysis revealed a significant association between pancreatitis and DPP-4 inhibitors; however, no such association was observed for GLP-1RAs.
BACKGROUND: The link of acute pancreatitis (AP) with Incretin based therapies (IBTs) in type 2 diabetes has existed since United States Food and Drug Administration alert in 2010. This issue still remains unresolved due to conflicting results among studies. RESEARCH DESIGN AND METHODS: We performed a systematic search of the PubMed, Embase, and Cochrane Library databases until 31 July 2019, and retrieved all cardiovascular outcome trials (CVOTs) of IBTs conducted for ≥12 months that reported the pre-specified and or pre-adjudicated pancreatitis outcomes. Subsequently, we conducted a meta-analysis to study the risk of AP observed with IBT in CVOTs. RESULTS: A meta-analysis of seven CVOTs of GLP-1 receptor agonists (GLP-1RAs) compared with placebo (N = 55,932) found no significant increase in AP (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.77-1.42; p = 0.77). In contrast, meta-analysis of five CVOTs comparing DPP-4 inhibitors with placebo (N = 47,714) and six CVOTs comparing DPP-4 inhibitors with placebo or active comparator (N = 53,747), found a significant increase (OR, 1.81; 95% CI, 1.21-2.70; p = 0.04 and OR, 1.54; 95% CI, 1.08-2.18; p = 0.02, respectively) in AP without any significant heterogeneity. CONCLUSIONS: This meta-analysis revealed a significant association between pancreatitis and DPP-4 inhibitors; however, no such association was observed for GLP-1RAs.
Authors: Phil A Hart; David Bradley; Darwin L Conwell; Kathleen Dungan; Somashekar G Krishna; Kathleen Wyne; Melena D Bellin; Dhiraj Yadav; Dana K Andersen; Jose Serrano; Georgios I Papachristou Journal: Lancet Gastroenterol Hepatol Date: 2021-06-03