Introduction: Bullous pemphigoid (BP) is a chronic, autoimmune blistering disease occurring primarily in the elderly population. The pathogenesis of this condition has been strongly linked to the presence of circulating and tissue-bound autoantibodies against the basement membrane antigens BP180 and BP230. In most cases, the causative agent remains unidentified, but in a selected few, certain medications have been implicated in the pathogenesis of the disease. Dipeptidyl peptidase-4 inhibitors (-gliptins), in particular, which are used primarily in the treatment of diabetes mellitus, have been increasingly suspected to be a prime aggravating drug in the incidence of BP. Case summary: Bullous pemphigoid (BP) is a chronic autoimmune blistering disease mainly affecting the elderly population. While the pathogenesis has not yet been fully elucidated, it has been suggested that there is a correlation observed with certain groups of medications. Among drugs correlated with bullous pemphigoid, the group of dipeptidyl peptidase-4 inhibitors (-gliptins) used in the treatment of diabetes mellitus has been one of the most strongly associated. This is a case of a 64-year-old female on regular maintenance medications including linagliptin who developed generalized pruritus followed a week after by appearance of localized fluid-filled vesicles and bullae on the right lower leg. BP associated with dipeptidyl peptidase-4 inhibitors is characterized as “non-inflammatory” – lesions are localized and associated with less erythema compared to the classic presentation. Serum eosinophilia was absent, and serum autoantibody against BP180 was positive. Histopathologic and immunohistologic results revealed characteristics similar to classic bullous pemphigoid. The association of dipeptidyl peptidase-4 inhibitors to the development of BP was observed to have a long latency period between initiation of drug to onset of lesions. There was significant improvement after both withdrawal of the drug and standard steroids and doxycycline. Unlike other drug-induced BP, dipeptidyl peptidase-4 inhibitor-associated BP was found to have similar prognosis with the classic manifestation as the patient noted recurrence one month after remission despite withdrawal of inciting drug. Conclusion: There has been increasing incidence in DPP-4 inhibitor-associated BP. Though its clinical course is similar to classic BP, a non-inflammatory and more localized presentation would prompt suspicion of association with drug. The long latency in DPP-4 inhibitor and lesion onset suggests that rather than being simply an adverse reaction to treatment, DPP-4 inhibitor-associated BP should be viewed as a drug-associated or drug-aggravated disease. Determining the association of BP to DPP4-inhibitors is significant as the management for these patients not only entails standard management of BP but also withdrawal of the suspect drug, which in this case was found to significantly improve the patient’s lesions after one month. Unlike other drug-induced BP, however, DPP-4 inhibitor associated BP was found to have the same prognosis with classic BP as the patient noted recurrence one month after remission.
Dipeptidyl-Peptidase IV Inhibitors ; Pemphigoid, Bullous ; Pharmaceutical Preparations ; Dipeptidyl-Peptidase IV Inhibitors ; Hypoglycemic Agents

No abstract available.
Dipeptidyl-Peptidase IV Inhibitors ; Myocardial Infarction ; Cardiovascular Diseases ; Dipeptidyl Peptidase 4 ; Diabetes Mellitus, Type 2

INTRODUCTION: Bullous pemphigoid (BP) is a chronic, relapsing autoimmune blistering disorder commonly found in adults older than 60 years of age. It is mediated by autoantibodies directed against the hemidesmosomal proteins BP180 and BP230, which trigger an inflammatory cascade leading to blister formation. BP may present with pruritus, followed by an erythematous plaque or urticaria, and subsequently by bullae formation with or without mucosal involvement. It develops sporadically but can also be triggered by ultraviolet light exposure, radiation therapy, and medications such as dipeptidyl peptidase-4 inhibitor (DPP4i). Since 2006, the increasing use of DPP4i (also known as gliptins) for their good safety profi le in treating Type II Diabetes Mellitus has led to a further increase in the incidence of bullous pemphigoid.

CASE REPORT: This is a case of a 65-year-old hypertensive and diabetic elderly Filipino female presenting DPP4i (linagliptin)-induced bullous pemphigoid with an atypical dyshidrosiform pattern, negative direct immunofluorescence (DIF), and Enzyme-linked immunosorbent assay (ELISA) that is negative for anti-BP180 antibodies but positive for anti-BP230 antibodies.

CONCLUSION: The increasing use of DPP4i for diabetes mellitus for its good safety profile may be an essential contributing factor to the increasing incidence of BP in elderly hypertensive and diabetic patients with a simultaneous increasing incidence of atypical BP presentations such as the dyshidrosiform variant. Inability to recognize these factors carries significant therapeutic implications, including prolonged multidrug immunosuppression and increased patient morbidity and mortality.

KEYWORDS: Bullous pemphigoid, gliptin, ELISA

Dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose co-transporter 2 (SGLT2) inhibitors are newer classes of glucose-lowering agents that are currently widely used in clinical practice. Their glycemic efficacy and cardiovascular safety have been well proven, and recent large clinical trials even have shown cardiovascular benefits of SGLT2 inhibitors. However, data regarding drug-related long-term safety remain inconclusive. Recently, several safety issues related to DPP-4 inhibitors and SGLT2 inhibitors have been raised by cardiovascular outcome trials or post-marketing pharmacoepidemiological studies. In this review, we summarize emerging safety issues regarding the use of DPP-4 inhibitors and SGLT2 inhibitors in type 2 diabetes and suggest how to interpret and apply these results to clinical practice.
Diabetes Mellitus ; Dipeptidyl-Peptidase IV Inhibitors ; Glucose* ; Sodium*

Survival from pancreatic cancer remains poor. Conventional treatment has resulted in only marginal improvements in survival compared with survival in the previous several decades. Thus, considerable interest has emerged regarding the potential use of common pharmaceutical agents as chemopreventative and chemotherapeutic options. Aspirin, metformin, statins, β-blockers, and bisphosphonates have biologically plausible mechanisms to inhibit pancreatic neoplasia, whereas dipeptidyl-peptidase 4 inhibitors may promote it. Regardless, real-world epidemiological data remain inconclusive. This review examines the hypotheses, evidence, and current state of the literature for each of these medications and their potential roles in the prevention and treatment of pancreatic cancer.
Adenocarcinoma ; Aspirin ; Dipeptidyl-Peptidase IV Inhibitors ; Diphosphonates ; Epidemiology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Metformin ; Pancreas ; Pancreatic Neoplasms*

Recent advances in understanding insulin secretion, action and signaling have led to the development of new pharmacological agents. Several new emerging drugs and drug classes for the management of diabetes are under development, including the incretin mimetic agents (exenatide, dipeptidyl peptidase 4 inhibitors, and glucagon-like peptide 1 analogues), the amylin analogue pramlintide, the cannabinoid-1 receptor antagonist rimonabant, the mixed peroxisome proliferator-activated receptor agonists muraglitazar and the inhaled insulin preparation Exubera. New drugs and technologic advances being made available will help achieve the goals of treating patients with diabetes to all the appropriate metabolic targets. Longer term studies will help providers weigh the benefits, adverse effects, cost, and unknown long-term risks of these medications.
Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptide 1 ; Humans ; Incretins ; Insulin ; Islet Amyloid Polypeptide ; Peroxisomes

BACKGROUND: To evaluate resource use and health costs due to the combination of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with diabetes and renal impairment in routine clinical practice. METHODS: An observational, retrospective study was performed. Patients aged > or =30 years treated with metformin who initiated a second oral antidiabetic treatment in 2009 to 2010 were included. Two groups of patients were analysed: metformin+DPP-4 inhibitors and other oral antidiabetics. The main measures were: compliance, persistence, metabolic control (glycosylated hemoglobin< 7%) and complications (hypoglycemia, cardiovascular events) and total costs. Patients were followed up for 2 years. RESULTS: We included 395 patients, mean age 70.2 years, 56.5% male: 135 patients received metformin+DPP-4 inhibitors and 260 patients received metformin+other oral antidiabetics. Patients receiving DPP-4 inhibitors showed better compliance (66.0% vs. 60.1%), persistence (57.6% vs. 50.0%), and metabolic control (63.9% vs. 57.3%), respectively, compared with those receiving other oral antidiabetics (P<0.05), and also had a lower rate of hypoglycemia (20.0% vs. 47.7%) and lower total costs (euro 2,486 vs. euro 3,002), P=0.001. CONCLUSION: Despite the limitations of the study, patients with renal impairment treated with DPP-4 inhibitors had better metabolic control, lower rates (association) of hypoglycaemia, and lower health costs for the Spanish national health system.
Compliance ; Dipeptidyl-Peptidase IV Inhibitors ; Health Care Costs ; Humans ; Hypoglycemia ; Hypoglycemic Agents ; Male ; Metformin* ; Retrospective Studies

BACKGROUND: The use of dipeptidyl peptidase-4 (DPP-4) inhibitors is increasing among renal transplant patients with diabetes. However, the glucose-lowering efficacies of various DPP-4 inhibitors and their effects on blood cyclosporine levels have not been fully investigated. We compared the glucose-lowering efficacies of DPP 4 inhibitors and evaluate their effects on the blood levels of cyclosporine in renal transplant recipients with diabetes. METHODS: Sixty-five renal allograft recipients who received treatment with DPP-4 inhibitors (vildagliptin, sitagliptin, or linagliptin) following kidney transplant were enrolled. The glucose-lowering efficacies of the DPP-4 inhibitors were compared according to the changes in the hemoglobin A1c (HbA1c) levels after 3 months of treatment. Changes in the trough levels of the cyclosporine were also assessed 2 months after treatment with each DPP-4 inhibitor. RESULTS: HbA1c significantly decreased in the linagliptin group in comparison with other DPP-4 inhibitors (vildagliptin –0.38%±1.03%, sitagliptin –0.53%±0.95%, and linagliptin –1.40±1.34; P=0.016). Cyclosporine trough levels were significantly increased in the sitagliptin group compared with vildagliptin group (30.62±81.70 ng/mL vs. –24.22±53.54 ng/mL, P=0.036). Cyclosporine trough levels were minimally changed in patients with linagliptin. CONCLUSION: Linagliptin demonstrates superior glucose-lowering efficacy and minimal effect on cyclosporine trough levels in comparison with other DPP-4 inhibitors in kidney transplant patients with diabetes.
Allografts ; Cyclosporine* ; Diabetes Mellitus ; Dipeptidyl-Peptidase IV Inhibitors ; Humans ; Hyperglycemia* ; Kidney ; Kidney Transplantation ; Pilot Projects* ; Transplantation

Recently, dipeptidylpeptidase-4 (DPP-4) inhibitors have been widely used as a second-line therapy for type 2 diabetes because of their glucose-lowering efficacy, weight neutral effects and minimal hypoglycemia. However, there have been concerns regarding the lack of evidence of the long-term consequences of DPP-4 inhibitors on cardiovascular disease, acute pancreatitis and cancers; therefore, the effects of DPP-4 inhibitors on these three major diseases are reviewed in this article. A growing body of evidence demonstrates the cardioprotective role of DPP-4 inhibitors in animal and small clinical studies. However, clearly conflicting data regarding the effects of DPP-4 inhibitors on cancers and pancreatitis have been presented in preclinical and epidemiologic studies. The forthcoming long-term clinical studies on cardiovascular safety will provide more conclusive answers relating to the safety of DPP-4 inhibitors, including their effects on cancer and pancreatitis.
Animals ; Cardiovascular Diseases ; Cardiovascular System ; Dipeptidyl-Peptidase IV Inhibitors ; Hypoglycemia ; Pancreatitis

Type 2 diabetes mellitus (T2DM) is a progressive disorder caused by a combination of insulin resistance and betacell dysfunction. The role of new hormones and systems in maintaining blood glucose homeostasis has recently been recognized. This recognition has led to the development of several novel classes of medications, including the incretin mimetic agents (glucagon like polypeptide-1 analogs and dipeptidyl peptidase IV inhibitors), the amylin analog and the endocannabinoid-1 receptor blocker. This review looks at these new agents in terms of their mode of action, pharmacokinetics and use in clinical practice. The new agents offer treatment options in select adult patients now, however, the efficacy and the safety has to be evaluated thoroughly by long term studies before the application to pediatric patients.
Adult ; Blood Glucose ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Dipeptidyl Peptidase 4 ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptides ; Homeostasis ; Humans ; Incretins ; Insulin Resistance ; Islet Amyloid Polypeptide