Prevalence of hepatic steatosis in patients with type 2 diabetes and response to glucose-lowering treatments. A multicenter retrospective study in Italian specialist care

Type 2 diabetes (T2D) is a risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD), which is becoming the commonest cause of chronic liver disease worldwide. We estimated MAFLD prevalence among patients with T2D using the hepatic steatosis index (HSI) and validated it against liver ultrasound. We also examined whether glucose-lowering medications (GLM) beneficially affected HSI

Transposition of cardiovascular outcome trial effects to the real-world population of patients with type 2 diabetes

BACKGROUND: Transferring results obtained in cardiovascular outcome trials (CVOTs) to the real-world setting is challenging. We herein transposed CVOT results to the population of patients with type 2 diabetes (T2D) seen in routine clinical practice and who may receive the medications tested in CVOTs. METHODS: We implemented the post-stratification approach based on aggregate data of CVOTs and individual data of a target population of diabetic outpatients. We used stratum-specific estimates available from CVOTs to calculate expected effect size for the target population by weighting the average of the stratum-specific treatment effects according to proportions of a given characteristic in the target population. Data are presented as hazard ratio (HR) and 95% confidence intervals. RESULTS: Compared to the target population (n = 139,708), the CVOT population (n = 95,816) was younger and had a two to threefold greater prevalence of cardiovascular disease. EMPA-REG was the CVOT with the largest variety of details on stratum-specific effects, followed by TECOS, whereas DECLARE and PIONEER-6 had more limited stratum-specific information. The post-stratification HR estimate for 3 point major adverse cardiovascular event (MACE) based on EMPA-REG was 0.88 (0.74-1.03) in the target population, compared to 0.86 (0.74-0.99) in the trial. The HR estimate based on LEADER was 0.88 (0.77-0.99) in the target population compared to 0.87 (0.78-0.97) in the trial. Consistent results were obtained for SUSTAIN-6, EXSCEL, PIONEER-6 and DECLARE. The effect of DPP-4 inhibitors observed in CVOTs remained neutral in the target population. CONCLUSIONS: Based on CVOT stratum-specific effects, cardiovascular protective actions of glucose lowering medications tested in CVOTs are transferrable to a much different real-world population of patients with T2D

Rationale and design of the DARWIN-T2D (DApagliflozin real world evIdeNce in Type 2 Diabetes). A multicenter retrospective nationwide Italian study and crowdsourcing opportunity

BACKGROUND: Randomized controlled trials (RCTs) in the field of diabetes have limitations inherent to the fact that design, setting, and patient characteristics may be poorly transferrable to clinical practice. Thus, evidence from studies using routinely accumulated clinical data are increasingly valued. AIMS: We herein describe rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes), a multicenter retrospective nationwide study conducted at 50 specialist outpatient clinics in Italy and promoted by the Italian Diabetes Society. DATA SYNTHESIS: The primary objective of the study is to describe the baseline clinical characteristics (particularly HbA1c) of patients initiated on dapagliflozin from marketing authorization approval to the end of 2016. Secondary and exploratory objectives will evaluate the changes in glycaemic and extraglycaemic efficacy parameters after initiation of dapagliflozin or after initiation of comparator glucose lowering medications (DPP-4 inhibitors, gliclazide extended release, and long-acting GLP-1 receptor agonists). An automated software will extract relevant data from the same electronic chart system at all centres, thereby minimizing data treatment and human intervention. CONCLUSION: The study is expected to collect an enormous dataset of information on dapagliflozin- and comparator-using patients. After study completion, the Italian Diabetes Society will launch an open crowdsourcing call on the DARWIN-T2D database, challenging diabetes researchers to apply their ideas and approaches to address new unmet needs and knowledge gaps in diabetes. We believe this will move DARWIN-T2D to the next generation of real world studies

Short-term effectiveness of dapagliflozin versus DPP-4 inhibitors in elderly patients with type 2 diabetes: a multicentre retrospective study

Aim: To compare effectiveness of dapagliflozin versus DPP-4 inhibitors on individualized HbA1c targets and extra-glycaemic endpoints among elderly patients with type 2 diabetes (T2D). Methods: This was a multicentre retrospective study on patients aged 70-80 years with HbA1c above individualized target and starting dapagliflozin or DPP-4 inhibitors in 2015-2017. The primary outcome was the proportion reaching individualized HbA1c targets. Confounding by indication was addressed by inverse probability of treatment weighting (IPTW), multivariable adjustment (MVA), or propensity score matching (PSM). Results: Patients initiating dapagliflozin (n = 445) differed from those initiating DPP-4i (n = 977) and balance between groups was achieved with IPTW or PSM. The median follow-up was 7.5 months and baseline HbA1c was 8.3%. A smaller proportion of patients initiating dapagliflozin attained individualized HbA1c target as compared to those initiating DPP-4 inhibitors (RR 0.73, p < 0.0001). IPTW, MVA, and PSM yielded similar results. Between-group difference in the primary outcome was observed among patients with lower eGFR or longer disease duration. Dapagliflozin allowed greater reductions in body weight and blood pressure than DPP-4 inhibitors. Conclusions: Elderly patients with T2D initiating dapagliflozin had a lower probability of achieving individualized HbA1c targets than those initiating DPP-4 inhibitors but displayed better improvements in extra-glycaemic endpoints

Phenotyping normal kidney function in elderly patients with type 2 diabetes: a cross-sectional multicentre study

AIMS: Type 2 diabetes (T2D) accelerates the decline in glomerular function; however, some individuals do not develop chronic kidney disease despite advanced age and long-lasting T2D. We aimed to phenotype patients with T2D aged 80 years or older who presented with a fully preserved kidney function. METHODS: From an Italian population of 281,217 T2D outpatients, we collected data on demographics, anthropometrics, diabetes duration, HbA1c, fasting plasma glucose, lipids, liver enzymes, estimated glomerular filtration rate (eGFR), albumin excretion rate (AER), chronic complications, and medication use. We primarily compared patients with a fully preserved kidney function (eGFR\u2009>\u200990 ml/min/1.73 m2 and AER\u2009<\u200930 mg/24 h, or G1A1) with those with mild kidney impairment (eGFR 60-90 ml/min/1.73 m2 and AER\u2009<\u200930 mg/24 h, or G2A1). RESULTS: N\u2009=\u2009113,860 had available data for eGFR and AER, 21,648 of whom were aged\u2009 65\u200980. G1A1 (n\u2009=\u2009278) and G2A1 (n\u2009=\u20096647) patients represented 1.3 and 30.7% of aged T2D patients, respectively, with an average diabetes duration of 16 years. Differences between the G1A1 and G2A1 groups were entered in a multiple logistic regression analysis with and without imputation of missing data. After adjustment and in both imputed and non-imputed datasets, younger age, lower BMI and lower triglycerides were associated with fully preserved versus mildly impaired kidney function. The comparison between G1A1 and G1A2/3 yielded different results. CONCLUSIONS: In a rare population of patients with a fully preserved kidney function despite old age and long-lasting diabetes, lower BMI and triglycerides suggest that protection from lipotoxicity may preserve kidney function over time

Short-term effectiveness of dapagliflozin versus DPP-4 inhibitors in elderly patients with type 2 diabetes: a multicentre retrospective study

Aim To compare effectiveness of dapagliflozin versus DPP-4 inhibitors on individualized HbA1c targets and extra-glycaemic endpoints among elderly patients with type 2 diabetes (T2D).Methods This was a multicentre retrospective study on patients aged 70-80 years with HbA1c above individualized target and starting dapagliflozin or DPP-4 inhibitors in 2015-2017. The primary outcome was the proportion reaching individualized HbA1c targets. Confounding by indication was addressed by inverse probability of treatment weighting (IPTW), multivariable adjustment (MVA), or propensity score matching (PSM).Results Patients initiating dapagliflozin (n = 445) differed from those initiating DPP-4i (n = 977) and balance between groups was achieved with IPTW or PSM. The median follow-up was 7.5 months and baseline HbA1c was 8.3%. A smaller proportion of patients initiating dapagliflozin attained individualized HbA1c target as compared to those initiating DPP-4 inhibitors (RR 0.73, p &lt; 0.0001). IPTW, MVA, and PSM yielded similar results. Between-group difference in the primary outcome was observed among patients with lower eGFR or longer disease duration. Dapagliflozin allowed greater reductions in body weight and blood pressure than DPP-4 inhibitors.Conclusions Elderly patients with T2D initiating dapagliflozin had a lower probability of achieving individualized HbA1c targets than those initiating DPP-4 inhibitors but displayed better improvements in extra-glycaemic endpoints