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Gut Aug 2017The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP.
DESIGN
Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined.
RESULTS
A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking.
CONCLUSIONS
PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.
Topics: Dietary Fats; Enzyme Therapy; Enzymes; Exocrine Pancreatic Insufficiency; Feces; Humans; Nutritional Status; Pancreas; Pancreatitis, Chronic; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 27941156
DOI: 10.1136/gutjnl-2016-312529 -
PloS One 2020A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with...
OBJECTIVE
A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations.
METHODS
A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency.
RESULTS
Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis.
DISCUSSION
Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations.
REGISTRATION
CRD42017060473.
Topics: Acute Disease; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Pancreatitis; Pharmaceutical Preparations
PubMed: 32302358
DOI: 10.1371/journal.pone.0231883 -
Critical Care (London, England) Mar 2023Current practice guidelines for optimal infusion rates during early intravenous hydration in patients with acute pancreatitis (AP) remain inconsistent. This systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current practice guidelines for optimal infusion rates during early intravenous hydration in patients with acute pancreatitis (AP) remain inconsistent. This systematic review and meta-analysis aimed to compare treatment outcomes between aggressive and non-aggressive intravenous hydration in severe and non-severe AP.
METHODS
This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We systematically searched PubMed, Embase and Cochrane Library for randomized controlled trials (RCTs) on November 23, 2022, and hand-searched the reference lists of included RCTs, relevant review articles and clinical guidelines. We included RCTs that compared clinical outcomes from aggressive and non-aggressive intravenous hydration in AP. Meta-analysis was performed using a random-effects model for participants with severe AP and non-severe AP. Our primary outcome was all-cause mortality, and several secondary outcomes included fluid-related complications, clinical improvement and APACHE II scores within 48 h.
RESULTS
We included a total of 9 RCTs with 953 participants. The meta-analysis indicated that, compared to non-aggressive intravenous hydration, aggressive intravenous hydration significantly increased mortality risk in severe AP (pooled RR: 2.45, 95% CI: 1.37, 4.40), while the result in non-severe AP was inconclusive (pooled RR: 2.26, 95% CI: 0.54, 9.44). However, aggressive intravenous hydration significantly increased fluid-related complication risk in both severe (pooled RR: 2.22, 95% CI 1.36, 3.63) and non-severe AP (pooled RR: 3.25, 95% CI: 1.53, 6.93). The meta-analysis indicated worse APACHE II scores (pooled mean difference: 3.31, 95% CI: 1.79, 4.84) in severe AP, and no increased likelihood of clinical improvement (pooled RR:1.20, 95% CI: 0.63, 2.29) in non-severe AP. Sensitivity analyses including only RCTs with goal-directed fluid therapy after initial fluid resuscitation therapy yielded consistent results.
CONCLUSIONS
Aggressive intravenous hydration increased the mortality risk in severe AP, and fluid-related complication risk in both severe and non-severe AP. More conservative intravenous fluid resuscitation protocols for AP are suggested.
Topics: Humans; Pancreatitis; Administration, Intravenous; Treatment Outcome; Resuscitation; Fluid Therapy
PubMed: 36949459
DOI: 10.1186/s13054-023-04401-0 -
Annals of Palliative Medicine Oct 2021Nutritional support is very important in the treatment of severe acute pancreatitis, this study aimed to investigate the effect of total parenteral nutrition (TPN) and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nutritional support is very important in the treatment of severe acute pancreatitis, this study aimed to investigate the effect of total parenteral nutrition (TPN) and enteral nutrition (TEN) on the prognosis of patients with acute pancreatitis.
METHODS
The databases of PubMed, Embase, Cochrane Library, and Ovid were searched using the keywords acute pancreatitis, enteral nutrition, and parenteral nutrition to obtain the reports of randomized controlled trials (RCTs) published after 2000. After screening the articles according to the inclusion criteria, risk of bias of the included literatures was evaluated using the Cochrane Handbook for Systematic Reviews. The software RevMan 5.3.5 was used for analysis and the creation of a forest plot and funnel plot.
RESULTS
A total of 488 literatures were preliminarily searched in this study, from which 10 articles were included into the final quantitative analysis, involving a total of 699 participants. A total of 6 literatures (n=329 participants) reported the infection rate indicators. The obtained statistic value [odds ratio (OR) =0.25, 95% confidence interval (CI): 0.10 to 0.62] showed TEN had less infection rate that TPN (P=0.003). A total of 8 studies (654 participants) reported the incidence rate indicators of multiple organ failure rate indicator, the obtained statistic value (OR =0.50, 95% CI: 0.24 to 1.08) showed no statistical difference between TEN and TPN (P>0.05). A total of 7 studies (550 participants) reported the mortality indicators. The obtained statistic value (OR =0.59, 95% CI: 0.37 to 0.94) showed TEN had less mortality than TPN (P=0.03). A total of 3 studies reported the length of hospital stay indicators. The obtained statistic value [mean difference (MD) -4.18, 95% CI: -5.07 to -3.30] showed the length of hospital stay for TEN was shorter that TPN (P<0.001).
DISCUSSION
Compared with TPN, TEN can reduce the incidence of infection, reduce the development of multiple organ failure, reduce mortality, and shorten the length of hospital stay in patients with severe acute pancreatitis (SAP). However, attention should be paid to prevent the occurrence of complications during the implementation of nutritional intervention.
Topics: Enteral Nutrition; Humans; Pancreatitis; Parenteral Nutrition; Parenteral Nutrition, Total; Prognosis
PubMed: 34763439
DOI: 10.21037/apm-21-2469 -
The Journal of Trauma and Acute Care... Nov 2022Timely management is critical for treating symptomatic common bile duct (CBD) stones; however, a single optimal management strategy has yet to be defined in the acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Timely management is critical for treating symptomatic common bile duct (CBD) stones; however, a single optimal management strategy has yet to be defined in the acute care setting. Consequently, this systematic review and network meta-analysis, comparing one-stage (CBD exploration or intraoperative endoscopic retrograde cholangiopancreatography [ERCP] with simultaneous cholecystectomy) and two-stage (precholecystectomy or postcholecystectomy ERCP) procedures, was undertaken with the main outcomes of interest being postprocedural complications and hospital length of stay (LOS).
METHODS
PubMed, SCOPUS, MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were methodically queried for articles from 2010 to 2021. The search terms were a combination of medical subject headings terms and the subsequent terms: gallstone; common bile duct (stone); choledocholithiasis; cholecystitis; endoscopic retrograde cholangiography/ERCP; common bile duct exploration; intraoperative, preoperative, perioperative, and postoperative endoscopic retrograde cholangiography; stone extraction; and one-stage and two-stage procedure. Studies that compared two procedures or more were included, whereas studies not recording complications (bile leak, hemorrhage, pancreatitis, perforation, intra-abdominal infections, and other infections) or LOS were excluded. A network meta-analysis was conducted to compare the four different approaches for managing CBD stones.
RESULTS
A total of 16 studies (8,644 participants) addressing the LOS and 41 studies (19,756 participants) addressing postprocedural complications were included in the analysis. The one-stage approaches were associated with a decrease in LOS compared with the two-stage approaches. Common bile duct exploration demonstrated a lower overall risk of complications compared with preoperative ERCP, but there were no differences in the overall risk of complications in the remaining comparisons. However, differences in specific postprocedural complications were detected between the four different approaches managing CBD stones.
CONCLUSION
This network meta-analysis suggests that both laparoscopic CBD exploration and intraoperative ERCP have equally good outcomes and provide a preferable single-anesthesia patient pathway with a shorter overall length of hospital stay compared with the two-stage approaches.
LEVEL OF EVIDENCE
Systematic Review/Meta Analysis; Level III.
Topics: Humans; Gallstones; Sphincterotomy, Endoscopic; Cholecystectomy, Laparoscopic; Network Meta-Analysis; Choledocholithiasis; Cholangiopancreatography, Endoscopic Retrograde; Common Bile Duct
PubMed: 35939370
DOI: 10.1097/TA.0000000000003755 -
Frontiers in Endocrinology 2023A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and... (Meta-Analysis)
Meta-Analysis
PURPOSE
A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity.
METHODS
A systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran's Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide. The safety outcomes of interest, including pancreatitis, the composite of gallbladder or biliary diseases, cholecystitis, and cholelithiasis and biliary diseases, were evaluated. (The composite of gallbladder or biliary diseases incorporated cholelithiasis, cholecystitis, other gallbladder disorders, and biliary diseases.).
RESULTS
A total of nine trials with 9871 participants (6828 in the tirzepatide group and 3043 in the control group) that met the pre-specified criteria were included. When compared to all control groups consisting of basal insulin (glargine or degludec), selective GLP1-RA (dulaglutide or semaglutide once weekly), and placebo, an increased risk of pancreatitis was not found to be significantly associated with tirzepatide (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436). For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases.
CONCLUSION
Based on the currently available data, tirzepatide appears to be safe regarding the risk of pancreatitis. However, the increased risk of the composite outcome of gallbladder or biliary diseases observed in RCTs warrants further attention from physicians in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023412400.
Topics: Humans; Cholecystitis; Diabetes Mellitus, Type 2; Insulin Glargine; Obesity; Pancreatitis; Cholelithiasis
PubMed: 37908750
DOI: 10.3389/fendo.2023.1214334 -
The Cochrane Database of Systematic... Mar 2020Nutrition is an important aspect of management in severe acute pancreatitis. Enteral nutrition has advantages over parenteral nutrition and is the preferred method of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nutrition is an important aspect of management in severe acute pancreatitis. Enteral nutrition has advantages over parenteral nutrition and is the preferred method of feeding. Enteral feeding via nasojejunal tube is often recommended, but its benefits over nasogastric feeding are unclear. The placement of a nasogastric tube is technically simpler than the placement of a nasojejunal tube.
OBJECTIVES
To compare the mortality, morbidity, and nutritional status outcomes of people with severe acute pancreatitis fed via nasogastric tube versus nasojejunal tube.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS on 17 October 2019 without using any language restrictions. We also searched reference lists and conference proceedings for relevant studies and clinical trial registries for ongoing trials. We contacted authors for additional information.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs comparing enteral feeding by nasogastric and nasojejunal tubes in participants with severe acute pancreatitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies for inclusion, assessed risk of bias of the included studies, and extracted data. This information was independently verified by the other review authors. We used standard methods expected by Cochrane to assess the risk of bias and perform data synthesis. We rated the certainty of evidence according to GRADE.
MAIN RESULTS
We included five RCTs that randomised a total of 220 adult participants from India, Scotland, and the USA. Two of the trial reports were available only as abstracts. The trials differed in the criteria used to rate the severity of acute pancreatitis, and three trials excluded those who presented in severe shock. The duration of onset of symptoms before presentation in the trials ranged from within one week to four weeks. The trials also differed in the methods used to confirm the placement of the tubes and in what was considered to be nasojejunal placement. We assessed none of the trials as at high risk of bias, though reporting of methods in four trials was insufficient to judge the risk of bias for one or more of the domains assessed. There was no evdence of effect with nasogastric or nasojejunal placement on the primary outcome of mortality (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.36 to 1.17; I = 0%; 5 trials, 220 participants; very low-certainty evidence due to indirectness and imprecision). Similarly, there was no evidence of effect on the secondary outcomes for which data were available. These included organ failure (3 trials, 145 participants), rate of infection (2 trials, 108 participants), success rate (3 trials, 159 participants), complications associated with the procedure (2 trials, 80 participants), need for surgical intervention (3 trials, 145 participants), requirement of parenteral nutrition (2 trials, 80 participants), complications associated with feeds (4 trials, 195 participants), and exacerbation of pain (4 trials, 195 participants). However, the certainty of the evidence for these secondary outcomes was also very low due to indirectness and imprecision. Three trials (117 participants) reported on length of hospital stay, but the data were not suitable for meta-analysis. None of the trials reported data suitable for meta-analysis for the other secondary outcomes of this review, which included days taken to achieve full nutrition requirement, duration of tube feeding, and duration of analgesic requirement after feeding tube placement.
AUTHORS' CONCLUSIONS
There is insufficient evidence to conclude that there is superiority, inferiority, or equivalence between the nasogastric and nasojejunal mode of enteral tube feeding in people with severe acute pancreatitis.
Topics: Enteral Nutrition; Humans; Intubation, Gastrointestinal; Length of Stay; Nutritional Status; Pancreatitis; Parenteral Nutrition; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32216139
DOI: 10.1002/14651858.CD010582.pub2 -
JAMA Surgery Jul 2018Several techniques are used for surgical treatment of gallstone disease with biliary duct calculi, but the safety and efficacy of these approaches have not been compared. (Comparative Study)
Comparative Study Meta-Analysis
Comparison of Efficacy and Safety of 4 Combinations of Laparoscopic and Intraoperative Techniques for Management of Gallstone Disease With Biliary Duct Calculi: A Systematic Review and Network Meta-analysis.
IMPORTANCE
Several techniques are used for surgical treatment of gallstone disease with biliary duct calculi, but the safety and efficacy of these approaches have not been compared.
OBJECTIVES
To compare the efficacy and safety of 4 surgical approaches to gallstone disease with biliary duct calculi.
DATA SOURCES
MEDLINE, Scopus, and ISI-Web of Science databases, articles published between 1950 and 2017 and searched from August 12, 2017, to September 14, 2017. Search terms used were LCBDE, LC, preoperative, ERCP, postoperative, period, cholangiopancreatography, endoscopic, retrograde, rendezvous, intraoperative, one-stage, two-stage, single-stage, gallstone, gallstones, calculi, stone, therapy, treatment, therapeutics, surgery, surgical, procedures, clinical trials as topic, random, and allocation in several logical combinations.
STUDY SELECTION
Randomized clinical trials comparing at least 2 of the following strategies: preoperative endoscopic retrograde cholangiopancreatography (PreERCP) plus laparoscopic cholecystectomy (LC); LC with laparoscopic common bile duct exploration (LCDBE); LC plus intraoperative endoscopic retrograde cholangiopancreatography (IntraERCP); and LC plus postoperative ERCP (PostERCP).
DATA EXTRACTION AND SYNTHESIS
A frequentist random-effects network meta-analysis was performed. The surface under the cumulative ranking curve (SUCRA) was used to show the probability that each approach would be the best for each outcome.
MAIN OUTCOMES AND MEASURES
Primary outcomes were the safety to efficacy ratio using overall mortality and morbidity rates as the main indicators of safety and the success rate as an indicator of efficacy. Secondary outcomes were acute pancreatitis, biliary leak, overall bleeding, operative time, length of hospital stay, total cost, and readmission rate.
RESULTS
The 20 trials comprised 2489 patients (and 2489 procedures). Laparoscopic cholecystectomy plus IntraERCP had the highest probability of being the most successful (SUCRA, 87.2%) and safest (SUCRA, 69.7%) with respect to morbidity. All approaches had similar results regarding overall mortality. Laparoscopic cholecystectomy plus LCBDE was the most successful for avoiding overall bleeding (SUCRA, 83.3%) and for the shortest operative time (SUCRA, 90.2%) and least total cost (SUCRA, 98.9%). Laparoscopic cholecystectomy plus IntraERCP was the best approach for length of hospital stay (SUCRA, 92.7%). Inconsistency was found in operative time (indirect estimate, 19.05; 95% CI, 2.44-35.66; P = .02) and total cost (indirect estimate, 17.06; 95% CI, 3.56-107.21; P = .04). Heterogeneity was observed for success rate (τ, 0.8), operative time (τ, >1), length of stay (τ, >1), and total cost (τ, >1).
CONCLUSIONS AND RELEVANCE
The combined LC and IntraERCP approach had the greatest odds to be the safest and appears to be the most successful. Laparoscopic cholecystectomy plus LBCDE appears to reduce the risk of acute pancreatitis but may be associated with a higher risk of biliary leak.
Topics: Cholangiopancreatography, Endoscopic Retrograde; Cholecystectomy, Laparoscopic; Choledocholithiasis; Cholelithiasis; Combined Modality Therapy; Gallstones; Humans; Network Meta-Analysis; Treatment Outcome
PubMed: 29847616
DOI: 10.1001/jamasurg.2018.1167 -
Nutrients Apr 2019Saffron is a natural compound that has been used for centuries in many parts of the world as a food colorant and additive. It was shown to have the ability to mitigate...
Saffron is a natural compound that has been used for centuries in many parts of the world as a food colorant and additive. It was shown to have the ability to mitigate various disorders through its known anti-inflammatory and anti-oxidant properties. Several studies have shown the effectiveness of saffron in the treatment of various chronic diseases like inflammatory bowel diseases, Alzheimer's, rheumatoid arthritis as well as common malignancies of the colon, stomach, lung, breast, and skin. Modern day drugs generally have unwanted side effects, which led to the current trend to use naturally occurring products with therapeutic properties. In the present review, the objective is to systematically analyze the wealth of information regarding the potential mechanisms of action and the medical use of saffron, the "golden spice", especially in digestive diseases. We summarized saffron influence on microbiome, molecular pathways, and inflammation in gastric, colon, liver cancers, and associated inflammations.
Topics: Carotenoids; Crocus; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Inflammation; Plant Extracts; Spices
PubMed: 31027364
DOI: 10.3390/nu11050943 -
The Lancet. Diabetes & Endocrinology Feb 2018Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular efficacy were varied. We aimed to examine overall cardiovascular efficacy for lixisenatide, liraglutide, semaglutide, and extended-release exenatide.
METHODS
In this systematic review and meta-analysis, we analysed data from eligible trials that assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in adult patients (aged 18 years or older) with type 2 diabetes and had a primary outcome including, but not limited to, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. We searched PubMed and MEDLINE without language restrictions up to Sept 18, 2017, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) for cardiovascular efficacy outcomes and odds ratios for key safety outcomes.
FINDINGS
Of 12 articles identified in our search and screened for eligibility, four trials of cardiovascular outcomes of GLP-1 receptor agonists were identified: ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN 6 (semaglutide), and EXSCEL (extended-release exenatide). Compared with placebo, GLP-1 receptor agonist treatment showed a significant 10% relative risk reduction in the three-point major adverse cardiovascular event primary outcome (cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke; HR 0·90, 95% CI 0·82-0·99; p=0·033), a 13% RRR in cardiovascular mortality (0·87, 0·79-0·96; p=0·007), and a 12% relative risk reduction in all-cause mortality (0·88, 0·81-0·95; p=0·002), with low-to-moderate between-trial statistical heterogeneity. No significant effect of GLP-1 receptor agonists was identified on fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospital admission for unstable angina, or hospital admission for heart failure. Overall, no significant differences were seen in severe hypoglycaemia, pancreatitis, pancreatic cancer, or medullary thyroid cancer reported between GLP-1 receptor agonist treatment and placebo.
INTERPRETATION
Our findings show cardiovascular safety across all GLP-1 receptor agonist cardiovascular outcome trials and suggest that drugs in this class can reduce three-point major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality risk, albeit to varying degrees for individual drugs, without significant safety concerns. GLP-1 receptor agonists have a favourable risk-benefit balance overall, which should allow the choice of drug to be individualised to each patient's needs.
FUNDING
Amylin Pharmaceuticals (AstraZeneca).
Topics: Cardiovascular Diseases; Cardiovascular System; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Prognosis; Survival Rate
PubMed: 29221659
DOI: 10.1016/S2213-8587(17)30412-6