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Purpose: An increasing body of evidence suggests that dipeptidyl-peptidase 4 (DPP-4) inhibitors could play a role in the development of bullous pemphigoid. The knowledge regarding this association is based on case reports, pharmacovigilance database analyses, and observational studies. Data from randomized clinical trials are a relevant source of information on adverse events. Since no single trial has a sufficient power to assess the risk of very rare adverse events, such as pemphigoid, metanalyses of RCTs could be a useful tool for exploring this issue. Methods: An extensive Medline, Embase and Cochrane Database search for sitagliptin or vildagliptin, omarigliptin or saxagliptin or alogliptin or trelagliptin or anagliptin or linagliptin or gemigliptin or evogliptin or teneligliptin was performed up to September 30th, 2019. All trials performed on type 2 diabetes, with duration ≥24 weeks, and comparing DPP4i with placebo or active drugs were collected. The study has been registered on PROSPERO (#153344). Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for pemphigoid. Results: A total of 138 eligible trials were identified (61,514 patients in DPP-4 inhibitors and 59,661 patients in the control group). Only six trials reported at least one case of pemphigoid (17 and 1 cases in DPP4i and control groups, respectively). DPP-4 inhibitors were associated with an increased risk of pemphigoid (MH-OR 4.44 [1.31, 15.00], p = 0.020). A separate analysis for trials with linagliptin showed a significant increase of BP with the active drug (MH-OR 4.69 [1.09, 20.22]; p = 0.04). Conclusions: In conclusion, available data from randomized controlled trials seem to confirm the association between DPP-4 inhibitors and bullous pemphigoid. This association could be limited to one molecule of the class (i.e., linagliptin), although data on other DPP4-i (e.g., vildagliptin) are insufficient to rule out similar detrimental effects. [ABSTRACT FROM AUTHOR]

Aims: Observational studies and meta-analyses of randomized trials on dipeptidyl peptidase-4 inhibitors (DPP4i) reported discordant results on the risk of malignancies with this class of drugs. Aim of the present meta-analysis is the assessment of the effect of DPP4i treatment on the incidence of different types of cancer, collecting all available evidence from randomized controlled trials. Methods: An extensive MEDLINE, EMBASE, and Cochrane database search for sitagliptin or vildagliptin or omarigliptin or saxagliptin or alogliptin or trelagliptin or anagliptin or linagliptin or gemigliptin or evogliptin or teneligliptin was performed up to September 30th, 2019. All trials performed on type 2 diabetes, with duration ≥ 24 weeks, and comparing of DPP4i with placebo or active drugs were collected. The study has been registered on PROSPERO (#153344). Mantel–Haenszel odds ratio (MH-OR) with 95% confidence interval (95% CI) was calculated for all outcomes. Results: A total of 157 eligible trials were identified. DPP-4i were not associated with an increased risk of overall cancer (MH-OR 0.93 [0.86, 1.00]; p = 0.07), with no significant differences across individual molecules of the class. When compared with placebo/none, a lower risk of cancer with DPP-4i was observed in placebo-controlled trials (MH-OR 0.90 [0.82, 0.99], p = 0.030), whereas no significant differences have been detected with any other comparators. DPP-4i was associated with a significant reduction in colorectal cancer (MH-OR 0.70 [0.53, 0.94], p = 0.020). Conclusions: Available data do not support the hypothesis of an association of DPP4i treatment with malignancies, with a possible beneficial effect for colon-rectal cancer. [ABSTRACT FROM AUTHOR]

Aims: The aim of the present meta-analysis is the identification of the characteristics of patients, which predict the efficacy on HbA1c of glucagon-like peptide-1 receptor agonists (GLP-1 RA). Methods: A Medline and Embase search for 'exenatide' OR 'liraglutide' OR 'albiglutide' OR 'dulaglutide' OR 'lixisenatide' was performed, collecting randomized clinical trials (duration > 12 weeks) up to September 2016, comparing GLP-1 RA at the maximal approved dose with placebo or active drugs. Furthermore, unpublished studies were searched in the register. For meta-analyses, the outcome considered were 24- and 52-week HbA1c. Separate analyses were performed, whenever possible, for subgroups of trials based on several inclusion criteria. In addition, meta-regression analyses were performed for comparisons for which 10 or more trails were available. Results: A total of 92 trials fulfilling the inclusion criteria were identified. In placebo-controlled trials ( n = 41), the 24-week mean reduction of HbA1c with GLP-1 RA was − 0.75 [− 0.87; − 0.63]%. Shorter-acting molecules appear to be more effective in patients with lower fasting glucose, whereas longer-acting agents in patients with higher fasting hyperglycaemia. Obesity and duration of diabetes do not seem to moderate the efficacy of GLP-1 RA, whereas in non-Caucasians and older patients liraglutide could be less effective. At 52 weeks, only 9 placebo-controlled trials were available for preventing any reliable analyses. Conclusions: Using a variety of approaches (meta-analyses of subgroup of trials, meta-regression, systematic review of subgroup analyses in individual trials, and meta-analyses of subgroups of patients), we identified some putative predictors of efficacy of GLP-1 RA, which deserve further investigation. [ABSTRACT FROM AUTHOR]

Aims: Results with GLP1-receptor agonists (GLP-1RA) on microvascular complications of diabetes are contrasting. In trials designed for cardiovascular outcomes, both liraglutide and semaglutide were associated with a relevant reduction in the incidence and progression of nephropathy. On the other hand, in the same trials, semaglutide was associated with an increased progression of retinopathy, and a similar trend was observed for liraglutide. This meta-analysis is aimed at assessing the effects of GLP-1RA on retinopathy and nephropathy. Methods: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration >11 weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug. Results: Of the 113 trials fulfilling the inclusion criteria, 78 and 62 did not report information on retinopathy and nephropathy, respectively. Treatment with GLP1-RA was not associated with a significant increase in the incidence of retinopathy (MH-OR [95% CI] 0.92 [0.74-1.16]. p = 0.49). In subgroup analyses, GLP1-RA were associated with a lower risk of retinopathy in comparison with sulfonylureas. Cases of macular edema were reported only in nine trials with no sign of increased risk. GLP1-RA reduced the incidence of nephropathy with respect to comparators (MH-OR [95% CI] 0.74 [0.60-0.92]. p = 0.005). This difference was significant versus placebo, but not versus any class of active comparators. Conclusions: GLP1-RA appear to reduce the incidence and/or progression of nephropathy and to have no specific effect on retinopathy-with the notable exception of semaglutide, which could have a negative impact on the retina. [ABSTRACT FROM AUTHOR]

The article presents the study on the measurement of hemoglobin A1c (HbA1c) variation through HbA1c or glycated albumin (GA) measurement for the prediction of the treatment response among type 2 diabetes patients. The high performance liquid chromatography (HPLC) method was used to measure HbA1c. The results were enumerated and conclude the values of GA and HbA1c and the correlation of HbA1c on short- and long-term glycemia.

Aim: Basal insulin and DPP4 inhibitors are both possible options in patients with type 2 diabetes failing to oral drugs. The identification of clinical predictors of success with either one of the two approaches could be of help in personalizing therapy. Methods: The retrospective study was performed on a consecutive series of patients with type 2 diabetes ( n = 1,002) failing to at least one oral agent, who had been prescribed either basal insulin or DPP4 inhibitors in the previous 2 years, with a duration of follow-up of at least 6 months. Clinical predictors of success after 6 months from the beginning of second-line treatment were identified in the cohort. Results: Among patients receiving a prescription of basal insulin, the proportion of therapeutic success at 6 months was 26.5 %. At multivariate analysis, a higher age and BMI, and a lower duration of diabetes were associated with success, as well as treatment with acarbose; conversely, a history of ischemic heart disease was associated with failure. Prescription of DPP4 inhibitors produced a therapeutic success in 24.8 % of cases. At multivariate analysis, success was associated with a lower baseline HbA1c and duration of diabetes, and a higher BMI and comorbidity; in addition, a lower success rate was found in women after adjusting for other confounders. Conclusions: The present data support the view that insulin treatment is preferable in patients with severe hyperglycemia, failing to one or more drugs, whereas DPP4 inhibitors appear to be more useful in those with comorbid conditions. [ABSTRACT FROM AUTHOR]

In the manuscript, the events of nephropathy and retinopathy recorded for the LEADER trial (Marso et al. 2016) were erroneously imputed; the numbers reported in Table 1 for that trial refer to serious adverse events, and not to total events, as stated in Methods. The correct figures are 268 and 416 cases of nephropathy, and 106 and 92 cases of retinopathy in liraglutide and control arms, respectively. As a consequence, the overall risk (MH-OR [95% CI]) of nephropathy and retinopathy with GLP-1RA (vs all comparators) is 0.77 [0.67-0.88], p < 0.001, and 0.99 [0.80-1.21], p = 0.90, respectively. The analyses reported in Figs. 1 and 2 were also corrected and reported below, together with supplementary figures 3 and 5. Please note that liraglutide is associated with a significant reduction in the incidence of nephropathy, whereas for retinopathy the difference from placebo is no longer statistically significant. [ABSTRACT FROM AUTHOR]

The article presents information on the lowering of risks involved in limb amputation with the use of type 2 diabetes drug canagliflozin. Details related to it include a table with the statistics of the drugs and their effects, leg and finger amputation being among the adverse effects of the drugs, and the use of diabetes 2 type drug Empagliflozin are presented.