Type 2 diabetes mellitus and the risk of acute pancreatitis: A meta-analysis
ABSTRACT Epidemiological evidences indicate that individuals with diabetes may have an increased risk of acute pancreatitis. Therefore, we carried out a meta-analysis to examine the present evidence and to identify the association between type 2 diabetes mellitus and the risk of acute pancreatitis.
All observational studies and randomized-controlled trials evaluating the relationship between type 2 diabetes mellitus and the risk of acute pancreatitis were identified in PubMed (January 1966), Embase (January 1974), Web of Science (January 1986), and Cochrane Library, through March 2012. Relative risk with the corresponding 95% confidence interval was pooled using STATA 12.0.
A total of seven observational studies with 15 298 024 patients were identified for the meta-analysis. Meta-analysis of these observational studies showed that type 2 diabetes mellitus was associated with an increased risk of acute pancreatitis (relative risk=1.84; 95% confidence interval 1.45-2.33; P=0.000), with significant heterogeneity (P=0.000, I=93.7%). The positive association was consistent in subgroup analyses according to the study design, geographic area, and sex. Our sensitivity analyses also confirmed the stability of the association. No significant publication bias was observed.
These outcomes strongly support the relationship between type 2 diabetes mellitus and an increased risk of acute pancreatitis. More fundamental research should be carried out to elucidate the biological mechanisms.
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ABSTRACT: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) play an increasing role in the management of type 2 diabetes. Such incretin-based therapies offer some advantages over other glucose-lowering agents, but might be associated with an increased risk of acute pancreatitis. Areas covered: An extensive literature search was performed to analyze clinical cases of acute pancreatitis reported in the literature or to the Food and Drug Administration (FDA), in randomized clinical trials, and in observational studies with five DPP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin, alogliptin, and linagliptin. Expert opinion: An increased risk of pancreatitis has been reported in diabetic versus nondiabetic patients. Several anecdotal clinical cases of pancreatitis have been reported with sitagliptin and vildagliptin and an increased relative risk reported to the FDA with sitagliptin versus other comparators, but reporting bias cannot be excluded. In rather short-term clinical trials with well-selected diabetic patients, no increased risk of acute pancreatitis has been observed with any of the five commercialized DPP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin, alogliptin, and linagliptin. Similarly, real-life cohort studies showed no increased incidence of pancreatitis with gliptins compared with other glucose-lowering agents, a finding recently challenged by a case- control study. These results must be confirmed in postmarketing surveillance programs and in ongoing large prospective trials with cardiovascular outcomes.Expert Opinion on Drug Safety 04/2013; 12(4). DOI:10.1517/14740338.2013.793671 · 2.91 Impact Factor
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ABSTRACT: Introduction: Dipeptidyl peptidase (DPP)-4 inhibitors belong to one class of drugs that have been approved for treatment of type 2 diabetes (T2D) based on the glucose-lowering actions of the gastrointestinal hormone glucagon-like peptide (GLP)-1. Several different compounds are now available, and although their mechanism of action (inhibition of the catalytic activity of DPP-4) is the same, there are fundamental differences between them. Areas covered: The authors discuss the differences between different DPP-4 inhibitors and review their therapeutic efficacy and key safety data. The literature covered includes original studies and meta-analyses identified in PubMed, recent abstracts presented at major diabetes scientific conferences, and clinical trials registered at ClinicalTrials.gov. Expert opinion: Although there are some differences in the pharmacokinetic and pharmacodynamic profiles of the different DPP-4 inhibitors, all are small orally active compounds with broadly similar HbA1c-lowering efficacy. They improve glycaemic control in T2D, without increasing the risk of hypoglycaemia or causing weight gain. They can be used as monotherapy or in combination with other anti-diabetic therapies, including insulin, regardless of renal or hepatic function, and are efficacious across the spectrum of patients with T2D, including those with long-standing disease duration. DPP-4 inhibitors may also have beneficial effects beyond glycaemic control, although this remains to be demonstrated in purpose-designed clinical trials.Expert Opinion on Pharmacotherapy 08/2013; 14(15). DOI:10.1517/14656566.2013.824966 · 3.53 Impact Factor
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ABSTRACT: Diabetes mellitus (DM) is common in the general population and it poses a heavy burden to society in the form of long-term disability, healthcare use and costs. The pancreas is a key player in glucose homeostasis, but the occurrence of newly diagnosed DM after acute pancreatitis (AP), the most frequent disease of the pancreas, has never been assessed systematically. The aim of this study was to conduct a systematic literature review to determine the prevalence and time course of DM and related conditions after the first attack of AP as well as the impact of covariates. Relevant literature cited in three electronic databases (Scopus, EMBASE and MEDLINE) was reviewed independently by two authors. The main outcome measures studied were newly diagnosed prediabetes, DM, or DM treated with insulin. Pooled prevalence and 95% CIs were calculated for all outcomes. A total of 24 prospective clinical studies, involving 1102 patients with first episode of AP, met all the eligibility criteria. Prediabetes and/or DM was observed in 37% (95% CI 30% to 45%) individuals after AP. The pooled prevalence of prediabetes, DM and treatment with insulin after AP was 16% (95% CI 9% to 24%), 23% (95% CI 16% to 31%), and 15% (95% CI 9% to 21%), respectively. Newly diagnosed DM developed in 15% of individuals within 12 months after first episode of AP and the risk increased significantly at 5 years (relative risk 2.7 (95% CI 1.9 to 3.8)). A similar trend was observed with regard to treatment with insulin. The severity of AP, its aetiology, individuals' age and gender had minimal effect on the studied outcomes. Patients with AP often develop prediabetes and/or DM after discharge from hospital, and have a greater than twofold increased risk of DM over 5 years. Further studies are warranted to determine the optimal strategy for its detection and whether the risk of developing DM after AP can be reduced.Gut 08/2013; 63(5). DOI:10.1136/gutjnl-2013-305062 · 14.66 Impact Factor