Firenze, Italy
Firenze, Italy

Time filter

Source Type

Monami M.,University of Florence | Filippi L.,University of Florence | Ungar A.,University of Florence | Sgrilli F.,University of Florence | And 6 more authors.
Current Medical Research and Opinion | Year: 2013

Background: The aim of the present paper is to provide some further data on the relationship between β-blocker treatment and the incidence of cancer, using two different approaches (epidemiological study and meta-analysis of clinical trials). Methods: In a consecutive series of 1340 diabetic patients starting insulin therapy, 112 cases of cancer during a mean follow-up of 75.9 months were identified as first hospital admission or death. For each case, the controls were chosen randomly from those members of the cohort matched for age, sex and BMI. The main predefined analysis was the comparison of cases and controls for length of exposure to β-blockers and proportion of patients exposed using a conditional logistic regression which takes into account the matching structure. For the meta-analytic sub-study, an extensive search of Medline and the Cochrane Library (any date up to December 31st, 2011) was performed for all trials in which a β-blocker was used. Mantel-Haenszel Odds Ratios (MH-OR) with 95% confidence intervals for incident malignancies were calculated using a random effect model. Results: After adjusting for mean daily dose of glargine and metformin, and ischemic heart disease, exposure to β-blockers was associated with a reduced overall risk of cancer (HR 0.33 [0.13; 0.83], p=0.019; HR for each month of exposure 0.87 [0.77; 0.98], p=0.025). In the meta-analysis sub-study, performed on nine trials, β-blockers were associated with a non-significant trend toward lower risk of cancer (MH-OR 0.93 [0.86; 1.01], p=0.070). Study limitation: Limitations of the observational study are the small sample size that limits the statistical power of analyses, that it was performed on diabetic patients only, and that diagnoses of malignancies were derived from administrative data. Conclusions: In conclusion, this research seem to confirm a possible beneficial effect of β-blockers against the risk of cancer development. © 2013 Informa UK Ltd All rights reserved.


Monami M.,Careggi Teaching Hospital | Dicembrini I.,Obesity Agency | Antenore A.,Careggi Teaching Hospital | Mannucci E.,Diabetes Agency
Diabetes Care | Year: 2011

OBJECTIVE - Thiazolidinediones and insulin are associated with a higher risk of fractures in type 2 diabetic patients. Incretin hormones increase bone density in experimental models, but the effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on bone fractures has not been reported so far. RESEARCH DESIGN AND METHODS - A meta-analysis was performed including all randomized clinical trials with a duration of at least 24 weeks, enrolling patients with type 2 diabetes, comparing DPP-4 inhibitors with placebo or active drugs. RESULTS - Twenty-eight trials enrolling 11,880 and 9,175 patients for DPP-4 inhibitors and comparators, respectively, were included, reporting 63 fractures. DPP-4 inhibitors, compared with placebo or other treatments, were associated with a reduced risk of fractures (Mantel-Haenszel odds ratio [MH-OR] 0.60, 95% CI 0.37-0.99, P = 0.045), even after the exclusion of comparisons with thiazolidinediones or sulfonylureas (MH-OR 0.56, 0.33-0.93, P = 0.026). CONCLUSIONS - The present meta-analysis suggests that treatment with DPP-4 inhibitors could be associated with a reduced risk of bone fractures. © 2011 by the American Diabetes Association.


Monami M.,Careggi Teaching Hospital | Dicembrini I.,Obesity Agency | Mannucci E.,Diabetes Agency
Acta Diabetologica | Year: 2014

Recent epidemiological data have contributed to the formulation of the hypothesis about the long-term safety of pioglitazone, a thiazolidinedione (TZD), with respect to malignancies, in particular bladder cancer. The primary aim of this meta-analysis of randomized clinical trials, not designed a priori to test this hypothesis, was to explore whether TZDs affect the risk of cancer. A meta-analysis was performed including published and unpublished randomized trials with a duration of at least 52 weeks, enrolling patients with or without diabetes, comparing TZDs with either placebo or other drug therapies on various different outcomes. We found 22 trials reporting at least one cancer and enrolling 13,197 patients to TZD (pioglitazone: n = 3,710 and rosiglitazone: n = 9,487) and 12,359 to placebo or active comparator groups. The mean follow-up was 26.1 months. Overall, those assigned at random to TZDs had a significant reduction (MH-OR 0.85 [0.73-0.98]; p = 0.027) in the incidence of malignancies, with no significant difference in effect between pioglitazone and rosiglitazone. Specifically, subgroup analyses showed a significant reduction for rosiglitazone (MH-OR 0.82 [0.69-0.98]; p = 0.029), but not for pioglitazone (MH-OR 0.66 [0.34-1.28]; p = 0.22). In further subgroup analyses of site-specific malignancies based on the data from four trials, the risk of bladder cancer with pioglitazone (MH-OR) was 2.05 [0.84-5.02]; p = 0.12. Further, rosiglitazone, but not pioglitazone, was associated with a significantly reduced risk of bowel cancer. In contrast, pioglitazone, but not rosiglitazone, was associated with a significant reduction in breast cancer. The present meta-analysis of trials, not designed a priori to test the hypothesis, provides reassuring evidence that TZDs are not associated with risk of overall malignancies. In fact, they are compatible with the possibility of a decreased risk of cancer. In site-specific subgroup analyses, for rosiglitazone, there was a significant decreased risk of bowel cancer. Subgroup analyses for pioglitazone did not allow to exclude an increased risk of bladder cancer, while the risk of breast cancer was significantly decreased. While these data are also useful to formulate not test hypotheses, they provide somewhat more cogent evidence than the previously published epidemiological data. © 2013 Springer-Verlag Italia.


Monami M.,Careggi Teaching Hospital | Ahren B.,Lund University | Dicembrini I.,Obesity Agency | Mannucci E.,Diabetes Agency
Diabetes, Obesity and Metabolism | Year: 2013

Aims: Preliminary data from randomized trials with metabolic outcomes have shown that treatment with dipeptidyl peptidase-4 inhibitors (DPP4i) could be associated with a reduced incidence of major cardiovascular events (MACE). The present meta-analysis is aimed at verifying this protective effect, collecting all available data from randomized trials. Methods: A comprehensive search for published and unpublished trials with a duration ≥24 weeks comparing DPP4i with placebo or other drugs was performed, retrieving all MACE reported as serious adverse events together with death from any cause. Mantel-Haenzel odds ratio (MH-OR) was calculated with random effect models for MACE, myocardial infarction, stroke and mortality. When available, effects on glycated haemoglobin, lipid profile and blood pressure were also assessed and used for the estimation of the modification of risk for myocardial infarction using the UKPDS risk engine. Results: A total of 70 trials, enrolling 41959 patients with a mean follow-up of 44.1 weeks, was collected and included in the analysis. The MH-OR (95% Confidence Interval) was 0.71[0.59;0.86], 0.64[0.44;0.94], 0.77[0.48;1.24] and 0.60[0.41;0.88] for MACE, myocardial infarction, stroke and mortality, respectively. Conclusions: Treatment with DPP4i reduces the risk of cardiovascular events (particularly myocardial infarction) and all-cause mortality in patients with type 2 diabetes. The reduction in the incidence of myocardial infarction is greater than what predicted on the basis of conventional risk factors, suggesting a role for other mechanisms. © 2012 Blackwell Publishing Ltd.


Monami M.,Careggi Teaching Hospital | Dicembrini I.,Obesity Agency | Martelli D.,Careggi Teaching Hospital | Mannucci E.,Diabetes Agency
Current Medical Research and Opinion | Year: 2011

Objective: Dipeptidyl peptidase-4 inhibitors (DPP4i) have been recently associated with increased risk of pancreatitis and cancer. The aim of the present meta-analysis of randomized clinical trials is the assessment of the effect of DPP4i on the incidence of major cardiovascular events (MACE), cancer, and pancreatitis. Research design and methods: An extensive Medline and Embase search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin', and 'dutogliptin' was performed, collecting all randomized clinical trials on humans up to March 1, 2011. The present meta-analysis was therefore performed including all randomized clinical trials with a duration of at least 24 weeks, enrolling patients with type 2 diabetes, comparing DPP4i with either placebo or active drugs. Completed but still unpublished trials were identified through a search of www.clinicaltrials.gov, Food and Drug Administration, and European Medicines Agency website. Results: Fifty-three trials enrolling 20,312 and 13,569 patients for DPP4i and comparators, respectively, were included, reporting 176 malignancies, 257 MACE, and 22 pancreatitis. DPP4i, compared with placebo or other treatment, were associated with a similar risk of cancer (MH-OR 1.020 [0.7421.402]; p=0.90) and pancreatitis (0.786 [0.3571.734], p=0.55), and with a reduced risk of MACE (MH-OR 0.689 [0.5280.899], p=0.006). Conclusions: The present meta-analysis seems to exclude any relevant short term effect of DPP4i on the incidence of cancer and suggest a possible protection from cardiovascular events. This result should be interpreted with caution, as those events were not the principal endpoint, the trial duration was short, and the characteristics of patients included could be different from routine clinical practice. © 2011 Informa UK Ltd All rights reserved.


Monami M.,Careggi Teaching Hospital | Dicembrini I.,Obesity Agency | Dicembrini I.,Diabetes Agency | Nardini C.,Careggi Teaching Hospital | And 2 more authors.
Diabetes Research and Clinical Practice | Year: 2014

Aims: Several randomized trials with metabolic outcomes have reported that glucagon like peptide-1 receptor agonists (GLP-1 RA) could be associated with an increased risk of pancreatitis. The present meta-analysis aimed to examine this hypothesis. Methods: An extensive Medline, Embase, and Cochrane Database search for "exenatide", "liraglutide", "albiglutide", "taspoglutide", "dulaglutide", "lixisenatide", and "semaglutide" was performed up to March 31st, 2013. Inclusion criteria: (i) randomized trials, (ii) duration ≥12 weeks; (iii) on type 2 diabetes; and (iv) comparison of GLP-1RA with placebo or active drugs. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for pancreatitis. Results: 80 eligible trials were identified. Of these, 39 had not disclosed their findings or did not report any information on pancreatitis. The remaining 41 trials enrolled 14,972 patients, with a total exposure of 14,333 patient. ×. years (8353 and 5980 patient. ×. years for GLP-1 receptor agonists and comparators, respectively). The overall risk of pancreatitis was not different between GLP-1RA and comparators (MH-OR: 1.01[0.37; 2.76]; p=0.99). Conclusions: The present meta-analysis does not suggest any increase in the risk of pancreatitis with the use of GLP-1RA. However, it should be recognized that the number of observed cases of incident pancreatitis is very small and the confidence intervals of risk estimates are wide. © 2014 Elsevier Ireland Ltd.


Monami M.,Careggi Teaching Hospital | Dicembrini I.,Obesity Agency | Dicembrini I.,Diabetes Agency | Mannucci E.,Diabetes Agency
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2014

Background & aims: Recently, the SAVOR TIMI-53 (Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus - Thrombolysis in Myocardial Infarction-53) reported a significant increase in the risk of hospitalizations for heart failure in patients treated with saxagliptin in comparison with placebo. Aim of the present meta-analysis is the systematic collection and synthesis of information on treatment-emergent cases of acute heart failure described in randomized clinical trials with DPP4. Methods & results: Data sources: An extensive Medline, Embase, and Cochrane Database search for "vildagliptin", "sitagliptin", "saxagliptin", "alogliptin", "linagliptin", and "dutogliptin" was performed, collecting all randomized clinical trials on humans up to October 1st, 2013. Studies were included if they satisfied the following criteria: i) randomized trials, ii) duration ≥24 weeks; iii) on type 2 diabetes; iv) comparison of DPP4i with placebo or active drugs. The principal outcome was the effect of DPP4i on the incidence of acute heart failure. A total of 84 eligible trials was identified. The overall risk of acute heart failure was higher in patients treated with DPP4i in comparison with those treated with placebo/active comparators (MH-OR: 1.19[1.03; 1.37]; p=0.015). When trials with non-cardiovascular outcomes were analysed separately no signal of risk was detectable. Conclusion: Available data from RCTs suggest that DPP4i could be associated with an increased risk of heart failure, without any clear evidence of differences among drugs of the class. Although it is plausible that the risk is greater in some sub-populations of patients, current evidence is not yet sufficient to identify susceptible patients. © 2014 Elsevier B.V.


Monami M.,Careggi Teaching Hospital | Dicembrini I.,Obesity Agency | Dicembrini I.,Diabetes Agency | Mannucci E.,Diabetes Agency
Diabetes, Obesity and Metabolism | Year: 2014

Aim: Some observational studies reporting an increased risk of pancreatitis in association with Dipeptidyl Peptidase-4 inhibitors (DPP4i) have raised concerns on the overall safety of this class. Aim of the present meta-analysis is the systematic collection of information on pancreatitis in randomized clinical trials with DPP4i. Methods: Data Sources: an extensive Medline, Embase and Cochrane Database search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin' and 'dutogliptin' was performed up to 1 March 2013. Study Selection: studies were included if they satisfied the following criteria: (i) randomized trials, (ii) duration ≥12weeks, (iii) on type 2 diabetes and (iv) comparison of DPP4i with placebo or active drugs. The identification and the selection of studies, and the subsequent data extraction were performed independently by two authors. Mantel-Haenszel odds ratio with 95% Confidence Interval (MH-OR) was calculated for all the adverse events defined below. The principal outcome was the effect of DPP4i on the incidence of pancreatitis. Results: A total of 134 eligible trials were identified. The overall risk of pancreatitis and pancreatic cancer was not different between DPP4i and comparators (MH-OR: 0.93[0.51-1.69]; p=0.82). Conclusions: It should be recognized that the number of observed cases of incident pancreatitis is small and the confidence intervals of risk estimates are wide. However, the present meta-analysis do not suggest any increase in the risk of pancreatitis with DPP4i. © 2013 John Wiley & Sons Ltd.


Monami M.,Careggi Teaching Hospital | Adalsteinsson J.E.,Novo Nordisk AS | Desideri C.M.,Diabetes Agency | Ragghianti B.,Diabetes Agency | And 2 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2013

Background: The reduction of hemoglobin A1c (HbA1c) levels is recognized as a useful means of preventing diabetic complications. HbA1c results from both fasting and post-prandial glycemia, and therefore FPG and PPG could provide different, and independent, contributions to long-term outcomes. Aim of the present meta-analysis is the assessment of the effects of reduction of FPG and PPG on cardiovascular outcomes in randomized controlled trials. Methods: An extensive search of Medline was performed for all randomized trials with a duration of at least 52 weeks and performed on glucose-lowering agents. Differences in the incidence of cardiovascular events, and all-cause and cardiovascular mortality were assessed in trials comparing different treatments with a between-group difference in FPG or PPG at endpoint greater than 1mmol/l. Results: The Mantel-Haenszel Odds Ratio (MH-OR) for cardiovascular events and all-cause and cardiovascular mortality in patients on more intensive treatments, in trials with a between-group difference of PPG greater than 1mmol/l, was not significantly different from controls (MH-OR [95%CI] 0.90 [0.51-1.58] for MACE); on the contrary, more intensive treatment of FPG produced a significantly lower all-cause (MH-OR 0.90 [0.81-0.99], p=0.03) and cardiovascular (MH-OR 0.86 [0.76-0.97], p=0.012) mortality, with no significant effect on the incidence of major cardiovascular events. Conclusions: In conclusion, reduction of FPG is associated with reduced cardiovascular mortality. Data on PPG are still scarce, but they point in the same direction. © 2013 Elsevier B.V.

Loading Obesity Agency collaborators
Loading Obesity Agency collaborators