Hip and vertebral fracture risk after initiating antidiabetic drugs in Japanese elderly: a nationwide study.

INTRODUCTION: We aimed to clarify the risks of initiating antidiabetic drugs for fractures using a nationwide health insurance claims database (NDBJ). MATERIALS AND METHODS: Patients aged ≥ 65 years initiating antidiabetic drugs at the outpatient department were enrolled after a 180-day period without prescribed antidiabetic drugs and followed with during 2012-2018 using NDBJ. The adjusted hazard risks (HRs) of each antidiabetic drug (thiazolidine, alpha-glucosidase inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, glinide, and insulin) for fractures compared with biguanide were obtained adjusting for age, gender, polypharmacy, dementia, and the other antidiabetic drugs. RESULTS: The DPP-4 inhibitor was the most often prescribed antidiabetic drug followed by biguanide with prescribed proportions of 71.7% and 12.9%. A total of 4,304 hip fractures and 9,388 vertebral fractures were identified among the 966,700 outpatient participants. Compared with biguanide, insulin, alpha-glucosidase inhibitor, and DPP-4 inhibitor were related to increased hip fracture risks. Vertebral fracture risk was higher in outpatients prescribed with insulin, thiazolidine, and DPP-4 inhibitor compared with biguanide. Patients prescribed insulin for hip and vertebral fractures' adjusted HRs were 2.17 (95% CI 1.77-2.66) and 1.45 (95% CI 1.24-1.70), respectively. Those prescribed DPP-4 inhibitor for hip and vertebral fractures' adjusted HRs were 1.27 (95% CI 1.15-1.40) and 1.20 (95% CI 1.12-1.28), respectively. CONCLUSIONS: Initiating insulin increased the risk of not only hip fractures but also vertebral fractures. Patients initiating antidiabetic drugs had increased risks of hip and vertebral fractures compared with those initiating biguanide independently for age, gender, polypharmacy, and dementia in the Japanese elderly.

Contact allergy to polyhexamethylene biguanide (polyaminopropyl biguanide).

BACKGROUND: Polyaminopropyl biguanide (INCI name) and polyhexamethylene biguanide (PHMB) are polymeric biguanides. PHMB is a broad-spectrum antimicrobial substance used as a preservative in many products. Due to our limited knowledge on PHMB contact allergy frequency and the fact that cases of allergic contact dermatitis to PHMB might be missed, we have included PHMB as a screening allergen since 2016. OBJECTIVE: To report the prevalence of positive patch test reactions to PHMB as a screening allergen in patients with suspected allergic contact dermatitis. METHODS: A retrospective analysis of 1760 patch tested patients from July 2016 to December 2018 was performed. Polyaminopropyl biguanide 2.0% aqua was included in the extended Malmö baseline series during the study period. RESULTS: Of all patients, 1204 (68.4%) were female. Positive patch test reactions were reported in 19 patients (1.1%). The most common sites of lesions were face, head, and neck (52.6%). There was a significant correlation between concomitant reactions to PHMB and other cosmetic-related allergens. CONCLUSION: The prevalence of positive reactions to PHMB was higher than that previously reported. Patch testing with PHMB should be performed in patients with dermatitis who have lesions on the face, head, and neck.

Insight into the Reaction of Alexidine with Sodium Hypochlorite: A Potential Error in Endodontic Treatment.

Therapeutic success in endodontic treatment depends on successful infection control. Alexidine dihydrochloride (ALX) was recently proposed as a potential alternative to 2% chlorhexidine (CHX) as it possesses similar antimicrobial properties, expresses substantivity and does not produce p-chloroaniline (PCA) when mixed with sodium hypochlorite (NaOCl). However, the products released in this reaction have not been described to date. The aim of this study was to identify detected chemical compounds formed in the reaction of ALX and NaOCl with the ultra-high-performance liquid chromatography-mass spectrophotometry (UHPLC-MS) method and assess whether precipitates and PCA are formed in this reaction. Solutions of ALX were mixed with the equivalent volume of 2% and 5.25% (w/v) NaOCl solutions. As control, 2% (w/v) CHX was mixed with 2% and 5.25% (w/v) NaOCl. Samples were subjected to the UHPLC-MS analysis. The mixture of ALX and NaOCl resulted in a yellowish precipitate formation, the amount of which depended on NaOCl concentration. Interaction of ALX and NaOCl resulted in the production of aliphatic amines. No PCA was formed when NaOCl was mixed with ALX. However, for the first time, we identified the possible products of the interaction. The interaction between NaOCl and ALX results in the formation of aliphatic amines; therefore, these compounds should not be mixed during endodontic treatment.

Tolerability and safety of urotainer® polihexanide 0.02% in catheterized patients: a prospective cohort study.

BACKGROUND: In patients with indwelling bladder catheters for > 2 weeks, bacterial colonization is inevitable, leading to urinary tract infections or encrustations with subsequent catheter blockage. Currently, bladder irrigations are the most frequently used prophylactic means, but the best solution remains yet to be determined. In vitro studies demonstrate that polihexanide is a promising option for catheter irrigation, but no data about safety and tolerability exist. METHODS: In a prospective observational study in patients with indwelling bladder catheter for > 2 weeks, a 0.02% polihexanide solution was used to rinse the catheter on five consecutive days. Adverse events, tolerability and vital signs were assessed before, during, after and at the end of the treatment period. RESULTS: There was no serious adverse event in the study. A total of 28 adverse events (AEs) in 15 (46.88%) participants were experienced. Absolute changes in pain scores were not clinically relevant. No incidences of either flushing or sweating were found during instillation. Bladder spasms during instillation were reported in two cases during a single instillation. Mean pulse rates did not change by more than 3 beats per minute. Mean changes in body temperature did not exceed 0.12 °C. Clinically relevant changes in blood pressure were recorded for 3 patients. CONCLUSIONS: This is the first study to demonstrate that a 0.02% polihexanide solution can safely be used for catheter irrigation. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02157415 ), June 6th, 2014.

A case of allergic contact dermatitis caused by Olanedine solution-A diagnostic patch-testing method involving dried filter paper.

BACKGROUND: Olanedine solution is a new antiseptic, and several cases of allergic contact dermatitis caused by the agent were reported in 2018; however, these cases were diagnosed based on positive results in 2-day closed patch testing of Olanedine solution "as is." OBJECTIVES: To present another case of Olanedine-induced allergic contact dermatitis and to analyze the optimal patch-testing method for this condition. METHODS: A 34-year-old Japanese female patient and 25 healthy control subjects were patch tested using wet filter paper, which had been treated with 15 µL Olanedine solution, and dried filter paper, which had been treated with 15 µL Olanedine solution and then dried. RESULTS: The patient and all of the control subjects exhibited false-positive reactions due to irritation in the 2-day closed patch tests with wet filter paper containing Olanedine solution "as is." The tests with dried filter paper produced a positive reaction on day 7 in the patient, and negative reactions in all control subjects. CONCLUSIONS: It is preferable to perform 2-day closed patch tests using filter paper with the test solution "as is," which had been dried before application in order to correctly diagnose antiseptic-induced allergic contact dermatitis.

Safety Assessment of Polyaminopropyl Biguanide (Polyhexamethylene Biguanide Hydrochloride) as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride), which functions as a preservative in cosmetic products. The Panel reviewed relevant data relating to the safety of this ingredient and concluded that Polyaminopropyl Biguanide is safe in cosmetics in the present practices of use and concentration described in the safety assessment, when formulated to be nonirritating and nonsensitizing, which may be based on a quantitative risk assessment or other accepted methodologies. The Panel also concluded that the data are insufficient to determine the safety of Polyaminopropyl Biguanide in products that may be incidentally inhaled.

Review of Biguanide (Metformin) Toxicity.

In the 1920s, guanidine, the active component of Galega officinalis, was shown to lower glucose levels and used to synthesize several antidiabetic compounds. Metformin (1,1 dimethylbiguanide) is the most well-known and currently the only marketed biguanide in the United States, United Kingdom, Canada, and Australia for the treatment of non-insulin-dependent diabetes mellitus. Although phenformin was removed from the US market in the 1970s, it is still available around the world and can be found in unregulated herbal supplements. Adverse events associated with therapeutic use of biguanides include gastrointestinal upset, vitamin B12 deficiency, and hemolytic anemia. Although the incidence is low, metformin toxicity can lead to hyperlactatemia and metabolic acidosis. Since metformin is predominantly eliminated from the body by the kidneys, toxicity can occur when metformin accumulates due to poor clearance from renal insufficiency or in the overdose setting. The dominant source of metabolic acidosis associated with hyperlactatemia in metformin toxicity is the rapid cytosolic adenosine triphosphate (ATP) turnover when complex I is inhibited and oxidative phosphorylation cannot adequately recycle the vast quantity of H+ from ATP hydrolysis. Although metabolic acidosis and hyperlactatemia are markers of metformin toxicity, the degree of hyperlactatemia and severity of acidemia have not been shown to be of prognostic value. Regardless of the etiology of toxicity, treatment should include supportive care and consideration for adjunct therapies such as gastrointestinal decontamination, glucose and insulin, alkalinization, extracorporeal techniques to reduce metformin body burden, and metabolic rescue.

Cardiovascular risks associated with dipeptidyl peptidase-4 inhibitors monotherapy compared with other antidiabetes drugs in the Japanese population: A nationwide cohort study.

PURPOSE: We evaluated the cardiovascular risk associated with dipeptidyl peptidase-4 inhibitors (DPP-4Is) as monotherapy compared with other antidiabetic drugs in Japan. METHODS: We conducted a nationwide cohort study involving 2 716 000 diabetes patients in Japan. New users of any antidiabetic drug as monotherapy between 1 April 2010 and 31 October 2014 were identified. Occurrences of myocardial infarction (MI), heart failure (HF), and stroke requiring hospitalization associated with DPP-4Is were compared with those associated with biguanides (BGs), sulfonylureas (SUs), or α-glucosidase inhibitors (α-GIs). Adjusted hazard ratios (aHRs) for these outcomes were estimated by Cox proportional hazards model. Propensity score standardization was used to control for confounding. RESULTS: We identified 1 105 103 patients using DPP-4Is, 278 280 patients using BGs, 273 449 patients using SUs, and 217 026 patients using α-GIs. The risks of MI and HF for DPP-4I users were significantly higher than those for BG users (MI: aHR, 1.48 [95%CI, 1.20-1.82], HF: aHR, 1.46 [95%CI, 1.31-1.62]), while significantly lower than those for SU users (MI: aHR, 0.84 [95%CI, 0.72-0.98], HF: aHR, 0.86 [95%CI, 0.81-0.92]). The risk of MI for DPP-4I users was similar to that for α-GI users, while the risk of HF for DPP-4I users was slightly higher than for α-GI users (MI: aHR, 0.98 [95%CI, 0.82-1.17], HF: aHR, 1.12[95%CI, 1.04-1.21]). CONCLUSIONS: Risk of MI and HF requiring hospitalization associated with DPP-4Is as monotherapy was significantly higher than BGs, significantly lower than SUs, and similar to α-GIs.

A Case of Severe Anaphylaxis to Polyhexanide: Cross-Reactivity between Biguanide Antiseptics.

We present the case of a 77-year-old female patient who suffered from severe anaphylaxis during wound care. Allergologic evaluation yielded specific IgE antibodies to chlorhexidine, but anaphylaxis to chlorhexidine was not congruent with the patient history and dermal provocation tests. However, skin prick tests provided evidence for a sensitization to polyhexanide that was further supported by the detection of specific IgE antibodies to polyhexanide, the results of basophil activation tests and IgE inhibition analysis. We presume cross-reactive IgE antibodies binding to both biguanide antiseptics and identified polyhexanide as the likely cause of the anaphylactic reaction. We recognize polyhexanide as an emerging allergen that has to be considered as a cause of anaphylaxis.

Should Side Effects Influence the Selection of Antidiabetic Therapies in Type 2 Diabetes?

PURPOSE OF REVIEW: There are currently over 40 different drugs in 12 distinct classes approved in the USA to treat patients with type 2 diabetes mellitus. This review summarizes our current knowledge about potential side effects of antidiabetic therapy and attempts to apply it to a clinical practice setting. RECENT FINDINGS: Given the heterogeneity of both the patients and the disease, it is mathematically impossible to test every available drug combination in long-term outcome, prospective, randomized blinded fashion before a clinician decides which agent(s) to prescribe to a specific patient in a given situation. To complicate the clinician's dilemma, there is lack of available tests to predict an individual's response or propensity to side effects. Further, the data available are derived from small, short-term registration trials and typically focus on relative rather than absolute risks of any given drug and do not address the potential adverse outcomes if a patient's diabetes remains untreated. Clinicians have to personalize their choice of antidiabetic therapy based both on the specific characteristics of the patient in front of them (stage of diabetes and its complications, overall health status, socioeconomic situation, other medications present, desire to improve control of diabetes, etc.) and the current knowledge about the relative and absolute balance of benefits and risks of any individual medication in that specific patient. It has to be recognized that this requires constant re-evaluation as database of our experience with antidiabetic therapy expands.

Randomized, placebo-controlled, double-blind clinical trial to evaluate the efficacy of polyhexanide for topical decolonization of MRSA carriers.

OBJECTIVES: The objective of this study was to evaluate the efficacy of polyhexanide (Prontoderm(®)) in eliminating MRSA carriage. METHODS: In a 1900 bed teaching hospital, MRSA-colonized patients were randomized into a double-blind, placebo-controlled superiority trial between January 2011 and July 2014. Patients were treated with either polyhexanide or placebo applied to the anterior nares (thrice daily) and skin (once daily) for 10 days. The primary outcome was MRSA decolonization at day 28 (D28) after the end of treatment assessed by ITT responder and PP analyses (microbiological follow-up ± 7 days and topical treatment ≥ 5 days). Secondary outcomes included safety, emergence of resistance and MRSA genotype changes. Registered trial number ISRCTN02288276. RESULTS: Of 2590 patients screened, 146 (polyhexanide group, 71; placebo group, 75) were included. ITT analysis showed that 24/71 (33.8%) patients in the polyhexanide group versus 22/75 (29.3%) in the placebo group were MRSA-free at D28 (risk difference, 4.5%; 95% CI, -10.6% to 19.5%; P = 0.56). PP analysis confirmed the results with 19/53 (35.8%) decolonized polyhexanide-treated patients versus 17/56 (30.4%) in the placebo arm (risk difference, 5.5%; 95% CI, -12.2% to 23%; P = 0.54). Nine serious adverse events occurred in the polyhexanide group versus 12 in the placebo group; none was attributable to study medication. Emergence of polyhexanide resistance or cross-resistance between polyhexanide and chlorhexidine was not observed. No case of exogenous recolonization by a genotypically different MRSA strain was documented. CONCLUSIONS: This study suggests that under real-life conditions, a single polyhexanide decolonization course is not effective in eradicating MRSA carriage.

Subgroup analysis of phase 3 studies of dulaglutide in Japanese patients with type 2 diabetes.

The efficacy and tolerability of once weekly dulaglutide 0.75 mg in Japanese patients with type 2 diabetes (T2D) were evaluated by subgroups defined by key demographic characteristics. This post hoc analysis included data from patients who received dulaglutide 0.75 mg for up to 26 weeks in three phase 3 trials (one open-label, randomized; one double-blind and open-label, randomized; one open-label, nonrandomized). Patients were classified into subgroups on the basis of sex (male, female), age (<65, ≥65 years), body weight (<70, ≥70 kg), body mass index (BMI; <25, ≥25 kg/m(2)), duration of diabetes (<7, ≥7 years), HbA1c (≤8.5, >8.5%), use of concomitant sulfonylurea (yes, no), and use of concomitant biguanide (yes, no). Efficacy measures analyzed were changes from baseline in HbA1c and body weight and percentages of patients achieving HbA1c <7.0%. Safety measures analyzed were incidence of hypoglycemia and nausea and change from baseline in seated pulse rate. A total of 855 patients were analyzed. Once weekly dulaglutide 0.75 mg improved blood glucose control as measured by HbA1c regardless of patient characteristics; patients with higher baseline HbA1c values had greater improvements compared to patients with lower baseline values. Weight loss was greater in patients with lower baseline HbA1c and in patients taking concomitant biguanides. Concomitant use of sulfonylureas had the greatest effect on the incidence of hypoglycemia. Treatment of T2D with once weekly dulaglutide 0.75 mg for 26 weeks was associated with significant improvement in glycemic control irrespective of age, sex, duration of diabetes, body weight, BMI, or concomitant medication.

Contact Lens Corneal Inflammatory Events in a University Population.

PURPOSE: To identify the contact lens-related modifiable and nonmodifiable factors associated with corneal inflammatory events (CIEs) in a university eye care center. METHODS: Contact lens-wearing undergraduate and graduate/professional students (age range, 18 to 36 years) with CIEs and contact lens wearers without complications (non-CIEs) were surveyed about their age, education level, overnight wear, brand of lens, brand of care solution, storage case age, topping-off, and lens replacement. Logistic regression was used to assess the impact of participant characteristics (demographic and behavior) and contact lens factors on the risk of a CIE. RESULTS: There were 160 participants enrolled, with 76 presenting with a CIE. Age was significant in the multivariate model (p < 0.001) as was an interaction between disinfectant and wearing schedule (p = 0.027). When daily wear (DW) and disinfectant were compared, polyquaternium-1/myristamidopropyl dimethylamine (PQ-1/MAPD) was associated with a greater risk of CIE versus peroxide (adjusted odds ratio [aOR], 18.4; 95% confidence interval [95% CI], 1.9-173.9) and versus polyhexamethylene biguanide or polyaminopropyl biguanide (PHMB) (aOR, 15.0; 95% CI, 4.5-50.0). For PHMB users only, extended wear (EW) compared with DW increased CIE risk (aOR, 10.0; 95% CI, 2.0-51.2). There was no difference in risk between EW and DW for PQ-1/MAPD (aOR, 0.8; 95% CI, 0.2, 2.6). CONCLUSIONS: The multivariate analysis suggests that younger age and the use of PQ-1/MAPD, particularly in DW, increase the risk of acquiring a CIE with soft contact lens wear in college-aged students. For PHMB users, EW compared with DW increases the risk of a CIE; but for PQ-1/MAPD users, there is no difference between EW and DW.

Polyhexanide - safety and efficacy as an antiseptic. / Polyheksanid - sikkerhet og effekt som antiseptikum.

BACKGROUND Polyhexamethylene biguanide hydrochloride/polyhexanide/polyaminopropyl biguanide (PHMB) is used as a disinfectant and antiseptic. This article discusses the use of the substance as an antiseptic. We summarise published data on its antimicrobial effect in vitro and its clinical effect and safety when used on skin, wounds and mucosa.MATERIAL AND METHOD A literature search was conducted in PubMed for articles published in the last five years. Articles available as of June 2014 were considered.RESULTS Of 332 articles identified, 27 were included. In vitro studies have demonstrated an antimicrobial effect on Gram-negative bacteria, Gram-positive bacteria and Candida albicans. The clinical studies are small, not well controlled and frequently sponsored by industry. Few adverse effects from the substance were reported.INTERPRETATION Better designed, larger-scale clinical studies of effect and safety are needed in order to give recommendations on the use of polyhexanide on skin, wounds and mucosa.

[POLYHEXAMETHYLENE BIGUANID HYDROCHLORIDE (BIGUANELLE) THERAPY OF BACTERIAL VAGINOSIS].

UNLABELLED: The aim of our study was to determine the efficacy and tolerability of local therapy with polyhexamethylene biguanid hydrochloride (BIGUANELLE) in women with anaerobic vaginal infection. MATERIAL AND METHODS: We include in our study 23 women (18-50) with established by AMSEL criteria bacterial vaginosis. In all of the women at the beginning and at the end of the survey was performed gynecological examination and microbiological research (AMSEL). The therapeutic scheme at all women is with a single vaginal application of gynecological solution BIGUANELLE. Effectiveness of the treatment was evaluated according to clinical complaints and microbiological research (Amsel criteria: Ph 4.5 >; KOH (+); "clue cells"; specific vaginal fluorine). Tolerability of patients to treatment was assessed by questionnaire. RESULTS: Clinical complaints of patients after the therapy decreased as follows: vaginal fluorine with 73.9%; odor--75%; pruritus--50%; discomfort--90%. Microbiological research and their evaluation by AMSEL, showed the therapeutic efficacy of the therapy in 16 (69.6%) of all (n-23) patients. At 7 (30.4%) women, the treatment remained without effect. At questionnaire answers, 73.9% patients were satisfied with the application of BIGUANELLE, 95.6% of them have implemented it easily, 95.6% of women believe that BIGUANELLE is more convenient to use in comparison with similar products which have a daily application, and none of the patients (100%) have any complaints in applying this gynecological solution. CONCLUSIONS: BIGUANELLE showed good clinical efficacy in the treatment of bacterial vaginosis. It is easily applied and well tolerated by the patients.

Opinion of the scientific committee on consumer safety (SCCS)--2nd Revision of the safety of the use of poly(hexamethylene) biguanide hydrochloride or polyaminopropyl biguanide (PHMB) in cosmetic products.

Conclusion of the opinion: On the basis of the data available, the SCCS concludes that Polyaminopropyl Biguanide (PHMB) is not safe for consumers when used as a preservative in cosmetic spray formulations and in all cosmetic products up to the maximum concentration of 0.3%. The safe use could be based on a lower use concentration and/or restrictions with regard to cosmetic products' categories. Dermal absorption studies on additional representative cosmetic formulations are needed. PHMB is used in a variety of applications other than cosmetics. General exposure data from sources others than cosmetics should be submitted for the assessment of the aggregate exposure of PHMB.

Systemic medication and intraocular pressure in a British population: the EPIC-Norfolk Eye Study.

OBJECTIVE: To determine the association between systemic medication use and intraocular pressure (IOP) in a population of older British men and women. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: We included 7093 participants from the European Prospective Investigation into Cancer-Norfolk Eye Study. Exclusion criteria were a history of glaucoma therapy (medical, laser, or surgical), IOP asymmetry between eyes of >5 mmHg, and missing data for any covariables. The mean age of participants was 68 years (range, 48-92) and 56% were women. METHODS: We measured IOP using the Ocular Response Analyzer. Three readings were taken per eye and the best signal value of the Goldmann-correlated IOP value considered. Participants were asked to bring all their medications and related documentation to the health examination, and these were recorded by the research nurse using an electronic case record form. The medication classes examined were angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, α-blockers, ß-blockers, calcium channel blockers, diuretics, nitrates, statins, insulin, biguanides, sulfonylureas, aspirin, and other nonsteroidal anti-inflammatory drugs. We examined associations between medication use and IOP using multivariable linear regression models adjusted for age, sex, and body mass index. Models containing diabetic medication were further adjusted for glycosylated hemoglobin levels. MAIN OUTCOME MEASURES: Mean IOP of the right and left eyes. RESULTS: Use of systemic ß-blockers (-0.92 mmHg; 95% CI, -1.19, -0.65; P<0.001) and nitrates (-0.63 mmHg; 95% CI, -1.12, -0.14; P = 0.011) were independently associated with lower IOP. The observed associations between statin or aspirin use with IOP were no longer significant after adjustment for ß-blocker use. CONCLUSIONS: This is the first population-based study to demonstrate and quantify clinically significant differences in IOP among participants using systemic ß-blockers or nitrates. Lower IOP observed in participants using statins or aspirin was explained by concurrent systemic ß-blocker use. The study findings may have implications for the management of glaucoma patients with comorbidity, and may provide insight into the pathophysiologic processes underlying IOP.

A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position.

The question whether antidiabetes drugs can cause acute pancreatitis dates back to the 1970s. Recently, old concerns have re-emerged following claims that use of incretins, a new class of drugs for type 2 diabetes, might increase the relative risk of acute pancreatitis up to 30-fold. Given that diabetes is per se a potent risk factor for acute pancreatitis and that drug-related acute pancreatitis is rare and difficult to diagnose, we searched the medical databases for information linking acute pancreatitis and type 2 diabetes drugs. Among the biguanides, both phenformin and metformin (the latter in patients with renal insufficiency) have been cited in case reports as a potential cause of acute pancreatitis. Sulphonylureas, as both entire class and single compound (glibenclamide), have also been found in cohort studies to increase its risk. No direct link was found between pancreatic damage and therapy with metaglinide, acarbose, pramlintide or SGLT-2 inhibitors. In animal models, thiazolinediones have demonstrated proprieties to attenuate pancreatic damage, opening perspectives for their use in treating acute pancreatitis in humans. Several case reports and the US Food and Drug Administration pharmacovigilance database indicate an association between acute pancreatitis and incretins, dipeptidyl peptidase-4 (DPP-4) inhibitors, and GLP-1 receptor agonists. To date, however, a clear-cut odds ratio for this association has been reported in only one of eight pharmacoepidemiological studies. Finally, none of the intervention trials investigating these compounds, including two large randomized controlled trials with cardiovascular endpoints, confirmed the purportedly increased risk of acute pancreatitis with incretin use.