Asociación entre penfigoide ampolloso e inhibidores de la dipeptidilpeptidasa-4: estudio de cohortes retrospectivo

BackgroundThe association between dipeptidyl peptidase 4 inhibitors (DPP-4i) and bullous pemphigoid (BP) has been demonstrated in several studies. The main aim of this study was to estimate the use of DPP-4i treatment in patients diagnosed with BP in our setting.MethodsWe selected patients histologically diagnosed with BP in our department between October 2015 and October 2018 and performed a retrospective chart review to assess clinical and epidemiological data and direct immunofluorescence (DIF) patterns.ResultsOf the 70 patients diagnosed with BP during the study period, 50% were diabetic and 88.57% of these were being treated with a DPP-4i when diagnosed with BP. The most common DPP-4i was linagliptin (used in 18.6% of patients), followed by vildagliptin (17.1%). The median latency period between initiation of DPP-4i treatment and diagnosis of BP was 27.5 months for all treatments, 16 months for linagliptin, and 39 months for vildagliptin (log rank < 0.01). A negative DIF result was significantly more common in patients not being treated with a DPP-4i. The DIF pattern most strongly (and significantly) associated with DPP-4i treatment was linear immunoglobulin G deposits along the dermal-epidermal junction. DPP-4i treatment was withdrawn in 87% of patients and 96% of these achieved a complete response.ConclusionsDPP-4i treatment is very common in patients with BP in our setting. The latency period between start of treatment and onset of BP seems to be shorter with linagliptin than with other types of gliptins. Patients receiving DPP-4i treatment may show different DIF patterns to those not receiving treatment.     

Long-term efficacy and safety of anti-hyperglycaemic agents in new-onset diabetes after transplant: Results from outpatient-based 1-year follow-up and a brief review of treatment options

Background and aimsEvaluation of long-term efficacy and safety of various anti-hyperglycaemic agents (AHA) for glycaemic control in NODAT, in stable kidney transplant recipients (KTRs) during 1-year outpatient follow-up.MethodsWe collected FPG, PPG, HbA1c, serum creatinine, eGFR, blood tacrolimus level, hypoglycaemia and body weight values from an existing database of KTRs diagnosed to have NODAT. Those newly initiated on AHA over 3 months post-transplant; received standard triple immunosuppressive therapy; and followed up for 1-year after referral, were included.ResultsIn ninety-five patients’ (Male = 65), mean decrease at 1-year from baseline in FPG (185.01 ± 62.11 mg/dL), PPG (293.21 ± 85.23 mg/dL) and HbA1c (8.48 ± 1.08%) was 67.09, 126.11 and 1.4 respectively (p < 0.0001). At 1-year, mean HbA1c was 7.08 ± 0.38%, ninety-one patients achieving HbA1c ≤ 7.5%. Fifty-two patients received oral combination therapy based on linagliptin/metformin/repaglinide/gliclazide, 19 received insulin-based regimen, and 24 received linagliptin monotharapey. Thirty patients reported hypoglycaemia (10 with gliclazide and 15 with insulin) and fifty patients gained body-weight at 1-year. Mean serum creatinine and eGFR significantly improved by 0.29 and 15.77 from baseline of 1.56 ± 0.62 mg/dL and 53.95 ± 16.10 mL/min/1.73 m² respectively.ConclusionsSignificant proportion of NODAT patients achieved long-term glycemic control with improved renal function. Combination therapy was needed in most within 1-year. Linagliptin monotherapy was effective, without producing hypoglycaemia or weight gain.     

A retrospective review of isolated gliptin-exposure cases reported to a state poison control system

Background. The dipeptidyl peptidase-4 (DPP-4) inhibitors sitagliptin, saxagliptin, and linagliptin are approved by the US Food and Drug Administration in the treatment of type-2 diabetes. Given the limited published information regarding human overdoses to these medications, our goal was to characterize such exposures. Methods. A state poison system database was retrospectively reviewed for all single-agent exposures to sitagliptin, saxagliptin, and linagliptin from 2006 to 2012. Case notes were reviewed and an observational case series was constructed from the data collected including age, weight, gender, circumstances surrounding exposure, symptoms, and outcome. Patients with co-ingestants, confirmed non-exposure, unknown outcomes, or other coding errors were excluded. Results. A total of 197 cases were identified: 135 cases were excluded (123 cases were excluded due to co-ingestants and 12 cases were lost to follow-up); 62 were included for review. No patients experienced hypoglycemia. One of 19 exposed pediatric (0–9 years of age) patients experienced symptoms and was safely managed at home after one episode of emesis. No symptom was experienced following unintentional ingestion by three adolescent (10–18 years of age) patients. Forty single-agent adult exposures to gliptins were included. Thirty-seven involved non-self-harm exposures resulting from double or triple doses; all were safely managed at home without reported symptoms. The majority of these ingestions involved sitagliptin. Three self-harm-adult exposures to gliptins were included for review. All the three were evaluated in a healthcare facility. One patient experienced abdominal discomfort after ingesting 700 mg of sitagliptin and was ultimately discharged from the emergency department. The other two patients experienced no reported symptoms. Conclusion. The majority of gliptin-exposed adult and pediatric/adolescent patients were safely managed at home and when evaluated in a healthcare facility, did not require hospitalization. Intentional self-harm-adult gliptin exposures were managed in a healthcare facility but rarely resulted in hospitalization or serious morbidity at doses up to 18 times the adult therapeutic dose. Additional studies are necessary to determine precise triage guidelines for the management of gliptin overdose.     

Clinical Effects of Exposure to DPP-4 Inhibitors as Reported to the National Poison Data System

DPP-4 inhibitors (sitagliptin, saxagliptin, and linagliptin) are approved for the treatment of diabetes. They are considered safe due to their hyperglycemia dependent mechanism of action. We examined all isolated exposures to DPP-4 inhibitors reported to the National Poison Database System since 2006 to determine if significant toxicity occurs after exposure with attention to pediatric and intentional overdoses. NPDS data regarding DPP-4 ingestions in all age groups between January 2006 and March 2013 was collected. Cases were reviewed, and the following inclusion criteria applied: (1) reported ingestion of a DPP-4 inhibitor and (2) known clinical outcome. Exclusion criteria included the following: (1) exposure to more than a single substance, (2) no known outcome, and (3) clinical outcome judged to be unrelated to the exposure. One thousand four hundred seventy-six cases were reviewed while 826 were excluded. Of 650 included cases, 562 developed no clinical effects. Mild effects were noted in 77. There were no deaths. Moderate/major effect cases were investigated: two medication-naive nondiabetic individuals with accidental exposures developed clinically significant hypoglycemia requiring treatment. One diabetic patient on a DPP-4 inhibitor developed prolonged hypoglycemia requiring admission and continuous exogenous dextrose. Of 650 included exposures to DPP-4 inhibitors, 639 (98.3%) had either no or minor clinical effects. Three resulted in clinically significant hypoglycemia requiring intervention. None of the moderate or major clinical outcomes were the result of intentional overdoses for the purpose of self-injury. No exploratory ingestions resulted in moderate or major effects. Based on this data, exposure to DPP-4 inhibitors may rarely result in clinically significant hypoglycemia.     

利格列汀联合二甲双胍治疗初诊2型糖尿病的效果研究

目的探究初诊2型糖尿病患者应用利格列汀联合二甲双胍治疗的临床效果。方法80例初诊2型糖尿病患者,随机分为对照组和观察组,各40例。对照组患者应用二甲双胍治疗,观察组在对照组基础上联合利格列汀治疗。对比两组患者血糖水平及不良反应发生情况。结果治疗后,观察组空腹血糖(6.5±0.7)mmol/L和餐后2 h血糖(8.6±1.7)mmol/L均低于对照组的(7.8±0.9)、(9.7±1.8)mmol/L,差异有统计学意义(P<0.05)。观察组不良反应发生率10.0%低于对照组的27.5%,差异有统计学意义(P<0.05)。结论利格列汀联合二甲双胍治疗2型糖尿病效果明显,可有效降低患者的血糖水平,安全性高。     

Empagliflozin/Linagliptin: Combination therapy in patients with type 2 diabetes

Glyxambi^® (empagliflozin/linagliptin) is a fixed-dose, once-daily tablet combining a sodium glucose co-transporter-2 (SGLT2) inhibitor with a dipeptidyl peptidase-4 (DPP-4) inhibitor. Glyxambi^® is served as an adjuvant to diet and exercise to improve glycemic control in adults with type 2 diabetes when both empagliflozin and linagliptin are appropriate treatments. Glyxambi^® combines 10 mg or 25 mg empagliflozin with 5 mg linagliptin, with different, complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes. Empagliflozin removes glucose through the urine by blocking blood glucose re-absorption in the kidney, and linagliptin exerts glucose-lowering activity by increasing hormones that stimulate the pancreas to produce more insulin and decreasing the levels of glucagon in the circulation. In addition, this combination therapy modestly reduces body weight and blood pressure without significant safety issues.     

Dipeptidyl peptidase-4: A key player in chronic liver disease

Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis. In addition to its peptidase activity, DPP-4 is known to be associated with immune stimulation, binding to and degradation of extracellular matrix, resistance to anti-cancer agents, and lipid accumulation. The liver expresses DPP-4 to a high degree, and recent accumulating data suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Furthermore, DPP-4 occurs in hepatic stem cells and plays a crucial role in hepatic regeneration. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor.