Similar effectiveness of dapagliflozin and GLP-1 receptor agonists concerning combined endpoints in routine clinical practice: A multicentre retrospective study

Aims According to cardiovascular outcome trials, some sodium-glucose contransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are recommended for secondary cardiovascular prevention in type 2 diabetes (T2D). In this real-world study, we compared the simultaneous reductions in HbA1c, body weight and systolic blood pressure after initiation of dapagliflozin or GLP-1RA as second or a more advanced line of therapy. Materials and methods DARWIN-T2D was a retrospective multi-centre study conducted at diabetes specialist clinics in Italy that compared T2D patients who initiated dapagliflozin or GLP-1RA (exenatide once weekly or liraglutide). Data were collected at baseline and at the first follow-up visit after 3 to 12 months. The primary endpoint was the proportion of patients achieving a simultaneous reduction in HbA1c, body weight and systolic blood pressure. To reduce confounding, we used multivariable adjustment (MVA) or propensity score matching (PSM). Results Totals of 473 patients initiating dapagliflozin and 336 patients initiating GLP-1RA were included. The two groups differed in age, diabetes duration, HbA1c, weight and concomitant medications. The median follow-up was 6 months in both groups. Using MVA or PSM, the primary endpoint was observed in 30% to 32% of patients, with no difference between groups. Simultaneous reduction of HbA1c, BP and SBP by specific threshold, as well as achievement of final goals, did not differ between groups. GLP-1RA reduced HbA1c by 0.3% more than the reduction achieved with dapagliflozin. Conclusion In routine specialist care, initiation of dapagliflozin can be as effective as initiation of a GLP-1RA for attainment of combined risk factor goals

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

Comparative effectiveness of exenatide once-weekly versus liraglutide in routine clinical practice: A retrospective multicentre study and meta-analysis of observational studies

In this study, we retrospectively compared the effectiveness of exenatide once-weekly (ExeOW) versus liraglutide in non-insulin treated patients with type 2 diabetes followed under routine care. We also present a meta-analysis of similar observational studies available in the literature. In our multicentre retrospective study, patients initiating ExeOW (n = 204) or liraglutide (n = 410) had similar baseline clinical characteristics. Change in HbA1c at 6 months was superimposable in the two groups ( 120.7% \ub1 1.0%), and changes in body weight were also similar (ExeOW -2.2 \ub1 3.7 kg; liraglutide 122.5 \ub1 4.3 kg; p = 0.457). Discontinuation rates were numerically but not significantly lower for ExeOW versus liraglutide. Pooling these data with those of observational studies available in the literature yielded superimposable effects between the two groups for the change in HbA1c and body weight, with a higher risk of discontinuation (mainly based on pharmacy refill rates) for ExeOW. We conclude that, in patients under routine care, initiation of ExeOW provides similar benefits on HbA1c and body weight as initiation of liraglutide. These data help view the results of randomized controlled trials from the perspective of their application in routine clinical practice

Type 2 diabetes mellitus pharmacological remission with dapagliflozin plus oral semaglutide

Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor and semaglutide, a glucagon-like peptide 1 receptor agonist, have both demonstrated efficacy in glycemic control, reducing blood pressure, body weight, risk of renal and heart failure in type 2 diabetes mellitus. In this observational, real-world, study we aimed to investigate the efficacy of the combination therapy with those two agents over glycemic control. We thus obtained the data of 1335 patients with type 2 diabetes followed by 11 Diabetes centers in Lombardia, Italy. A group of 443 patients was treated with dapagliflozin alone, the other group of 892 patients was treated with the combination therapy of dapagliflozin plus oral semaglutide. We analyzed changes in glycated hemoglobin from baseline to 6 months of follow-up, as well as changes in fasting glycemia, body weight, body mass index, systolic and diastolic pressure, heart rate, creatinine, estimated glomerular filtration rate and albuminuria. Both groups of patients showed an improvement of glycometabolic control after 6 months of treatment; indeed, the treatment with dapagliflozin plus oral semaglutide showed a reduction of glycated hemoglobin of 1.2% as compared to the 0.5% reduction observed in the dapagliflozin alone group. Significant changes were observed in body mass index, fasting plasmatic glucose, blood pressure, total cholesterol, LDL and albumin to creatinine ratio, with a high rate (55%) of near-normalization of glycated hemoglobin. Our real world data confirmed the potential of the oral combination therapy dapagliflozin with semaglutide in inducing pharmacological remission of type 2 diabetes mellitus

Similar effectiveness of dapagliflozin and GLP-1 receptor agonists concerning combined endpoints in routine clinical practice: A multicentre retrospective study

Aims According to cardiovascular outcome trials, some sodium-glucose contransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are recommended for secondary cardiovascular prevention in type 2 diabetes (T2D). In this real-world study, we compared the simultaneous reductions in HbA1c, body weight and systolic blood pressure after initiation of dapagliflozin or GLP-1RA as second or a more advanced line of therapy. Materials and methods DARWIN-T2D was a retrospective multi-centre study conducted at diabetes specialist clinics in Italy that compared T2D patients who initiated dapagliflozin or GLP-1RA (exenatide once weekly or liraglutide). Data were collected at baseline and at the first follow-up visit after 3 to 12 months. The primary endpoint was the proportion of patients achieving a simultaneous reduction in HbA1c, body weight and systolic blood pressure. To reduce confounding, we used multivariable adjustment (MVA) or propensity score matching (PSM). Results Totals of 473 patients initiating dapagliflozin and 336 patients initiating GLP-1RA were included. The two groups differed in age, diabetes duration, HbA1c, weight and concomitant medications. The median follow-up was 6 months in both groups. Using MVA or PSM, the primary endpoint was observed in 30% to 32% of patients, with no difference between groups. Simultaneous reduction of HbA1c, BP and SBP by specific threshold, as well as achievement of final goals, did not differ between groups. GLP-1RA reduced HbA1c by 0.3% more than the reduction achieved with dapagliflozin. Conclusion In routine specialist care, initiation of dapagliflozin can be as effective as initiation of a GLP-1RA for attainment of combined risk factor goals

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

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