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Background: International guidelines for diabetes care emphasize the urgency of promptly achieving and sustaining adequate glycemic control to reduce the occurrence of micro/macrovascular complications in patients with type 2 diabetes mellitus (T2DM). However, data from the Italian Association of Medical Diabetologists (AMD) Annals reveal that only 47% of T2DM patients reach appropriate glycemic targets, with approximately 30% relying on insulin therapy, either solely or in combination. This artificial intelligence analysis seeks to assess the potential impact of timely insulin initiation in all eligible patients via a "what-if" scenario simulation, leveraging real-world data. Methods: This retrospective cohort study utilized the AMD Annals database, comprising 1,186,247 T2DM patients from 2005 to 2019. Employing the Logic Learning Machine (LLM), we simulated timely insulin use for all eligible patients, estimating its effect on glycemic control after 12 months within a cohort of 85,239 patients. Of these, 20,015 were employed for the machine learning phase and 65,224 for simulation. Results: Within the simulated scenario, the introduction of appropriate insulin therapy led to a noteworthy projected 17% increase in patients meeting the metabolic target after 12 months from therapy initiation within the cohort of 65,224 individuals. The LLM's projection envisages 32,851 potential patients achieving the target (hemoglobin glycated < 7.5%) after 12 months, compared to 21,453 patients observed in real-world cases. The receiver operating characteristic (ROC) curve analysis for this model demonstrated modest performance, with an area under the curve (AUC) value of 70.4%. Conclusions: This study reaffirms the significance of combatting therapeutic inertia in managing T2DM patients. Early insulinization, when clinically appropriate, markedly enhances patients' metabolic goals at the 12-month follow-up. [ABSTRACT FROM AUTHOR]

Background and Aims: The COVID-19 pandemic affected the processes of routine care for chronic patients due to disrupted delivery care. The aim of the present study is to verify the COVID-19 pandemic effects on diabetes control and management.Methods and Results: The study was designed as a retrospective observational study, performed on two cohorts of patients with diabetes in 2019 and 2020. Data used for the analyses were gathered from administrative and laboratory databases, which do not include any sensible information on COVID-19. The Tuscany Regional Health Agency is data controller for current administrative databases and has been working to produce available information for policy decision-making. In 2020, in comparison with 2019, a relevant reduction of the number of patients measuring HbA1c was observed during the March-April lockdown, and again during the second pandemic wave in Autumn. A similar pattern was observed for specialist visits for diabetes, for which the introduction of televisits only partly compensated for the reduction of traditional office visits. The number of patients receiving drugs for diabetes each week in 2020 was very similar to 2019. The mean HbA1c values and the proportion of HbA1c values > 8% for each week, were higher during the 2020 Spring and Autumn lockdown.Conclusion: COVID-19 pandemic negatively impacts diabetes management, reducing specialist visits and HbA1c determinations during the first and second pandemic wave. Despite a satisfactory continuity in pharmacological treatment, short-term impairment of average glycemic control was detected, particularly in Autumn. [ABSTRACT FROM AUTHOR]

Aims: Meta-analyses of randomized trials on Dipeptidyl Peptidase-4 inhibitors (DPP4i) reported discordant results on major cardiovascular events (MACE), mortality, and heart failure. Aim of this meta-analysis of randomized trials is the assessment of the cardiovascular safety of DPP4i.Data Synthesis: A Medline, Embase, Cochrane database search for sitagliptin, vildagliptin, omarigliptin, saxagliptin, alogliptin, trelagliptin, anagliptin, linagliptin, gemigliptin, evogliptin, and teneligliptin was performed up to up January 1st, 2020. All trials with a duration ≥24 weeks and comparing the effects of DPP4i with placebo or active drugs were collected. Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all outcomes defined above. A total of 182 eligible trials were identified. DPP-4i were not associated with an increased risk of MACE (MH-OR 0.99 [0.93, 1.04]), all-cause mortality (MH-OR 0.99 [0.93, 1.06]), and heart failure (MH-OR 1.05 [0.96, 1.15]) with no significant differences across individual molecules, except for saxagliptin, which was associated with an increased risk of heart failure.Conclusions: As a class, DPP4i are not associated with any increase or reduction of MACE, all-cause mortality, and heart failure. Saxagliptin seems to be associated with an increased risk of hospitalization for heart failure. [ABSTRACT FROM AUTHOR]

Background and Aims: Glucagon-like Peptide 1 Receptor Agonists (GLP1-RA) has been associated with a reduction of major cardiovascular events (MACE) and mortality on the basis of the results of cardiovascular outcome trials (CVOT). Several meta-analyses on this issue have been recently published; however, they were all restricted to CVOT, with the exclusion of all studies designed for other endpoints; moreover, other cardiovascular endpoints, such as atrial fibrillation and heart failure have not been fully explored.Methods and Results: 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 ≥52 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. We included 43 trials, enrolling 63,134 patients. A significant reduction of MACE (MH-OR 0.87 [0.83, 0.92]), all-cause mortality (MH-OR 0.89 [0.83, 0.96]), and a nonstatistical trend toward reduction of heart failure (MH-OR 0.93 [0.85, 1.01]) was observed - GLP1-RA did not increase the risk of atrial fibrillation (MH-OR 0.94 [0.84, 1.04]).Conclusion: The present meta-analysis confirms the favorable effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events, cardiovascular and all-cause mortality, stroke, and possibly myocardial infarction. Conversely, the effects on heart failure remain uncertain. Available data on atrial fibrillation seems to exclude any major safety issues in this respect.Registration Number (prospero): CRD42018115577. [ABSTRACT FROM AUTHOR]

Aim: To conduct a meta‐analysis of cardiovascular outcome trials on the effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) on major adverse cardiovascular events (MACE). Methods: A search of MEDLINE, EMBASE, Cochrane database and clinicaltrials.gov was performed to identify controlled trials (up to 15 June 2019) of GLP‐1RAs with a cardiovascular endpoint. The principal endpoint of the present meta‐analysis was MACE; secondary endpoints included myocardial infarction, stroke, cardiovascular and all‐cause mortality, and hospitalization for heart failure. Mantel–Haenszel odds ratios (MH‐ORs) with 95% confidence intervals (CIs) were calculated for all outcomes. Results: In the seven trials included, all placebo‐controlled, GLP‐1RA treatment was associated with a reduction in MACE (MH‐OR 0.87 [95% CI 0.81, 0.93]). Cardiovascular and all‐cause mortality, myocardial infarction and stroke were also reduced (MH‐OR 0.88 [95% CI 0.80, 0.96], MH‐OR 0.90 [95% CI 0.82, 0.98], MH‐OR 0.91 [95% CI 0.84, 0.98] and MH‐OR 0.86 [95% CI 0.77, 0.97], respectively). Results for hospitalization for heart failure were not statistically significant (MH‐OR 0.93 [95% CI 0.83, 1.04]). The meta‐analyses of patient subgroups showed a significant reduction in MACE with GLP‐1RAs, irrespective of gender, advanced age and obesity. Conclusions: GLP‐1RAs are associated with a reduction in cardiovascular morbidity and mortality in high‐risk patients with diabetes. This effect does not appear to be moderated by gender or body mass index. The possibility of different effects of GLP‐1RAs between patients in primary and secondary prevention merits further investigation. [ABSTRACT FROM AUTHOR]

Background and Aim: The interpretation of discrepancies across cardiovascular safety trials (CVOT) with SGLT-2 inhibitors in the incidence of major cardiovascular events (MACE) and mortality is complex, because of heterogeneity in trial protocols and baseline characteristics of patients enrolled. Aim of this analysis is the exploration of possible determinants of heterogeneity of relative risk reduction for major cardiovascular events (MACE) and all-cause mortality.Methods and Results: Incidence of events (MACE and mortality) in intervention and control groups and baseline characteristics of patients were extracted for each trial (EMPAREG, CANVAS, and DECLARE). For studies including both primary and secondary prevention cohorts, those two subgroups were considered separately. Metaregression analysis was used to assess the association of relative risk reduction with baseline characteristics of patients, including observed incidence of events with placebo. The estimated reduction in the incidence of MACE associated with SGLT-2 inhibitors showed a significant association with the incidence of MACE in the control group, suggesting that a greater effect was observed in trials enrolling patients at higher risk (Slope -0.008 [-0.023; 0.007], p = 0.31). A higher proportion of patients treated with statins, β-blockers and insulin at baseline was associated with a greater reduction of MACE, but not of mortality.Conclusions: In CVOT trials, the magnitude of the effect of SGLT-2 inhibitors on MACE is driven by absolute risk of enrolled patients; as a consequence, the estimated risk reduction is lower in primary prevention cohorts, which have a lower risk. This result supports the hypothesis of a class effect of SGLT-2 inhibitors on MACE. [ABSTRACT FROM AUTHOR]

Aim: The aim of this meta‐analysis of randomized trials was to assess the effects of SGLT‐2i on the overall incidence of malignancies and on different types of cancer, summerizing the results of trials with a duration of at least 1 year. This was done in light of the effect of SGLT‐2 inhibitors (SGLT‐2is) that has been highlighted by some studies, showing an increased incidence of bladder cancer, particularly with use of empagliflozin. Materials and methods: A Medline and Embase search for "Canaglifozin", "Dapaglifozin", "Empaglifozin", "Ertuglifozin", "Ipraglifozin", Tofoglifozin" or "Luseoglifozin" was performed, identifying randomized trials with a duration of more than 52 weeks up to 1 December 2018 that compared SGLT‐2is with placebo or active comparators. The outcomes considered were all types of cancer and several site‐specific cancers (ie, breast, pulmonary, gastrointestinal, hepatic, pancreatic, skin, prostate and bladder). Mantel–Haenszel odds ratios with 95% Confidence Intervals (MH‐OR, 95% CI) were calculated for all outcomes. Results: A total of 27 trials fulfilled the inclusion criteria. Retrieved trials had enrolled 27 744 and 20 441 patients in SGLT‐2 inhibitor and comparator groups, respectively. No difference was observed in the incidence of all malignancies between patients allocated to SGLT‐2i and comparators (MH‐OR 0.98[0.77–1.24]). The incidence of bladder cancer, and of any other type of cancer, was not significantly increased by treatment with any SGLT‐2i. Conclusions: Available data from randomized trials do not suggest a detrimental effect of SGLT‐2is on the incidence of malignancies in general, or in bladder cancer in particular. [ABSTRACT FROM AUTHOR]

Aims: Sodium glucose co‐transport‐2 (SGLT‐2) inhibitors reduce tubular glucose reabsorption, producing a reduction of blood glucose without stimulating insulin release. The aim of this meta‐analysis was the systematic collection of available data from randomized trials, in order to establish the durability of the efficacy of SGLT‐2 inhibitors on glycaemic control and body mass index. Methods: A meta‐analysis was performed, including all trials with a duration of at least 12 weeks, comparing SGLT‐2 inhibitors with non‐SGLT‐2 inhibitor agents in type 2 diabetes. The principal outcome was the effect of SGLT‐2 inhibitors on hemoglobin A1c (HbA1c) at 12, 24, 52 and 104 weeks. Data on body mass index at the same time points were also collected. Results: Among 66 randomized trials, HbA1c reduction at 12, 24, 52 and 104 weeks was 0.63% (0.57; 0.68, 0.63% (0.57; 0.70), 0.66% (0.57; 0.74) and 0.60% (0.40; 0.81), respectively. SGLT‐2 inhibitors showed a greater efficacy than dipeptidyl‐peptidase‐4 inhibitors (DPP‐4i). Sulfonylureas appeared to be superior to SGLT‐2 inhibitors at 12 weeks, but not at 24 and 52 weeks; SGLT‐2 inhibitors produced a greater reduction in HbA1c than did sulfonylureas at 104 weeks. SGLT‐2 inhibitor‐induced weight loss in placebo‐controlled trials appeared to increase progressively with the duration of treatment. Conclusions: SGLT‐2 inhibitors showed a good persistence of efficacy, at least up to 2 years, with a small but significant superiority over DPP‐4i. Sulfonylureas are more effective in the very short term, but less effective in the longer term. [ABSTRACT FROM AUTHOR]

Background. Patient education is capable of reducing the risk for diabetic foot ulcers. However, specific education on foot ulcer prevention was either included in broader programs addressing different parts of diabetes care or provided with time- and resource-consuming curricula. The aim of the study is to assess the feasibility and efficacy of a brief educational program for the prevention of diabetic foot ulcers in high-risk patients. Methods. The study was performed on type 2 diabetic patients, randomized in a 1 : 1 ratio either to intervention or to control group. The principal endpoint was the incidence of foot ulcers. The intervention was a two-hour program provided to groups of 5–7 patients, including a 30-minute face-to-face lesson on risk factors for foot ulcers, and a 90-minute interactive session with practical exercises on behaviors for reducing risk. Results. The study was prematurely terminated due to a highly significant difference in outcome between the two treatment groups. The final sample was therefore composed of 121 patients. Six patients, all in the control group, developed ulcers during the 6-month follow-up (10% versus 0%, p=0.012). Conclusions. A brief, 2-hour, focused educational program is effective in preventing diabetic foot ulcers in high-risk patients. [ABSTRACT FROM AUTHOR]

Vaccine hesitancy (VH) has been identified as one of the major health concerns of our time by the World Health Organization. It may prove especially detrimental in the light of the ongoing SARS-CoV-2 pandemic, as vaccination campaigns still represent the primary strategy against the detrimental consequences of the pandemic. Among patients suffering from type 2 diabetes mellitus (DB), who are particularly vulnerable to COVID-19, VH might represent an even more serious threat. Therefore, our study focuses on identifying potential determinants of VH among patients with type 2 diabetes. Study participants (n = 1176) filled in a two-section online self-administered questionnaire, answering questions regarding demographic and anamnestic data, as well as their intention to accept any vaccination against COVID-19. Some possible reasons underlying VH were investigated as well. An overall hesitancy rate of 14.2% was registered. Data showed how older age, male gender, higher education level, and having been vaccinated for seasonal influenza in 2020–2021 were associated with a significantly higher propensity to receive the COVID-19 vaccine. On the contrary, having experienced adverse effects following past vaccinations was a negative predictor. In addition to confirming an array of predictors of VH, we found a worryingly high prevalence of VH among diabetics, who have been shown to be particularly exposed to severe COVID-19 and death. These findings may be useful in planning targeted action toward acceptance improvement and enhancing the efficacy of vaccination campaigns. [ABSTRACT FROM AUTHOR]

Background: Foot ulcers have a relevant economic impact on Health Care Systems and the cost-effectivenesseffectiveness of options is not clear. The aim of this study was the assessment of costs for ulcers treatment after 6, 12, and 18 months of follow-up, compared to those for major amputation. Methods: A retrospective study was carried out on 196 types 2 diabetic patients with foot ulcers. The principal endpoints were 1) the proportion of recovered patients among those with ulcers not healed after 6 and 12 months; 2) the assessment of direct costs for treatment of ulcers 6, 12, and 18 months of follow-up, as compared to the cost of major amputation. The economic evaluation was performed considering the perspective of the local health system. Results: Out of 196 patients, 85(46.2%), 131(71.6%), and 140(85.9%) healed within 6, 12, and 18 months, respectively. The average health cost during the 18-month follow-up was 5402€ per patient. We calculated hypothetical costs for three different scenarios, in which patients who did not heal within 6 months underwent a major amputation at 6, 1,2, or 18 months. Costs for the standard of care for all these scenarios (6,094, 7,256, and 7649€ for 6, 12, or 18 months, respectively) were significantly lower than that for major amputations (21,065€). Conclusions: A conservative approach appears more convenient than major amputations in ulcers not healing after 6 months, irrespective of the estimated risk of individual patients.