Effectiveness of oral semaglutide on glucose control and body weight up to 18 months: a multicenter retrospective real-world study.

AIM: Oral semaglutide, an innovative orally administered GLP-1 receptor agonist for type 2 diabetes (T2D) management was herein evaluated for its effectiveness in a multi-center retrospective real-world study. METHODS: We included new-users of oral semaglutide from 18 specialist care centres and collected retrospective data on baseline clinical characteristics. Updated values of HbA1c and body weight were analyzed using the mixed model for repeated measures. RESULTS: The study included 166 individuals with T2D, predominantly men (64.5%), with a mean age of 64.4 years and a mean diabetes duration of 10.1 years. In the majority of patients (68.3%) oral semaglutide was used as a second-line drug, mostly with metformin. At baseline, mean BMI was 28.9 kg/m2 and HbA1c was 7.5%. During the 18-month observation period, oral semaglutide demonstrated significant reductions in HbA1c, with a maximum change of - 0.9%, and 42.1% of patients achieved HbA1c values below 7.0%. Additionally, there was a substantial reduction in body weight, with an estimated change of - 3.4 kg at 18 months, and 30.3% of patients experienced a 5% or greater reduction in baseline body weight. Only 24.2% of patients reached the 14 mg dose. Subgroup analysis revealed that baseline HbA1c > 7%, persistence on drug, not being on a prior therapy with DPP-4 inhibitors, and loosing 5% or more the initial body weight were associated with greater HbA1c reductions. CONCLUSION: This study supports oral semaglutide as an effective option for T2D treatment, offering improved glucose control and weight management in a real-world setting.

Diabetes management in cancer patients. An Italian Association of Medical Oncology, Italian Association of Medical Diabetologists, Italian Society of Diabetology, Italian Society of Endocrinology and Italian Society of Pharmacology multidisciplinary consensus position paper.

Cancer management has significantly evolved in recent years, focusing on a multidisciplinary team approach to provide the best possible patient care and address the various comorbidities, toxicities, and complications that may arise during the patient's treatment journey. The co-occurrence of diabetes and cancer presents a significant challenge for health care professionals worldwide. Management of these conditions requires a holistic approach to improve patients' overall health, treatment outcomes, and quality of life, preventing diabetes complications and cancer treatment side-effects. In this article, a multidisciplinary panel of experts from different Italian scientific societies provide a critical overview of the co-management of cancer and diabetes, with an increasing focus on identifying a novel specialty field, 'diabeto-oncology', and suggest new co-management models of cancer patients with diabetes to improve their care. To better support cancer patients with diabetes and ensure high levels of coordinated care between oncologists and diabetologists, 'diabeto-oncology' could represent a new specialized field that combines specific expertise, skills, and training.

MiRNA dysregulation underlying common pathways in type 2 diabetes and cancer development: an Italian Association of Medical Oncology (AIOM)/Italian Association of Medical Diabetologists (AMD)/Italian Society of Diabetology (SID)/Italian Society of Endocrinology (SIE)/Italian Society of Pharmacology (SIF) multidisciplinary critical view.

Increasing evidence suggests that patients with diabetes, particularly type 2 diabetes (T2D), are characterized by an increased risk of developing different types of cancer, so cancer could be proposed as a new T2D-related complication. On the other hand, cancer may also increase the risk of developing new-onset diabetes, mainly caused by anticancer therapies. Hyperinsulinemia, hyperglycemia, and chronic inflammation typical of T2D could represent possible mechanisms involved in cancer development in diabetic patients. MicroRNAs (miRNAs) are a subset of non-coding RNAs, ⁓22 nucleotides in length, which control the post-transcriptional regulation of gene expression through both translational repression and messenger RNA degradation. Of note, miRNAs have multiple target genes and alteration of their expression has been reported in multiple diseases, including T2D and cancer. Accordingly, specific miRNA-regulated pathways are involved in the pathogenesis of both conditions. In this review, a panel of experts from the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) provide a critical view of the evidence about the involvement of miRNAs in the pathophysiology of both T2D and cancer, trying to identify the shared miRNA signature and pathways able to explain the strong correlation between the two conditions, as well as to envision new common pharmacological approaches.

Putative circulating adipose tissue-derived stem cells, obesity, and metabolic syndrome features.

PURPOSE: In mice, adipose tissue-derived stem cells (ASCs) reach the systemic circulation and establish ectopic adipose depots fostering insulin resistance, but whether this occurs in humans is unknown. We examined circulating ASCs in individuals with various combination of metabolic syndrome traits. METHODS: We enrolled patients attending a routine metabolic evaluation or scheduled for bariatric surgery. We quantified ASCs as CD34+CD45-CD31-(CD36+) cells in the stromal vascular fraction of subcutaneous and visceral adipose tissue samples and examined the presence and frequency of putative ASCs in peripheral blood. RESULTS: We included 111 patients (mean age 59 years, 55% males), 40 of whom were scheduled for bariatric surgery. The population of CD34+CD45-CD31- ASCs was significantly more frequent in visceral than subcutaneous adipose depots (10.4 vs 4.1% of the stromal vascular fraction; p < 0.001), but not correlated with BMI or metabolic syndrome traits. The same phenotype of ASCs was detectable in peripheral blood of 58.6% of patients. Those with detectable circulating ASCs had significantly higher BMI (37.8 vs 33.3 kg/m2; p = 0.003) and waist (111.2 vs 105.4 cm; p = 0.001), but no difference in other metabolic syndrome traits (p = 0.84). After bariatric surgery, patients with detectable circulating ASCs had greater BMI reductions at 6 months (- 10.4 vs - 7.8 kg/m2; p = 0.014). CONCLUSION: Presence of putative circulating ASCs, antigenically similar to those observed in the adipose tissue, is associated with greater adiposity and larger BMI reduction after surgery, but not with clinical signs of metabolic impairment. The role of circulating ASCs in adipose tissue biology and systemic metabolism deserves further investigation.

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.

Cardiometabolic indices predict hypogonadism in male patients with type 2 diabetes.

PURPOSE: To evaluate in men with type 2 diabetes the association of cardiometabolic indices [Visceral Adiposity Index (VAI), Triglyceride Glucose Index (TyG), and lipid accumulation product (LAP)] with total testosterone (TT) levels, and their predictive cut-off values in identifying hypogonadism. METHODS: 265 consecutive men aged 40-70 years with type 2 diabetes performed an andrological evaluation; metabolic parameters and TT were determined. Receiver operating characteristic (ROC) curves were used to identify cut-off values of cardiometabolic indices in predicting low testosterone (TT < 12 nmol/l). RESULTS: VAI, TyG, and LAP were negatively associated with TT levels. The prevalence of hypogonadism in men in the fourth quartiles of VAI, TyG, and LAP was ~ 70.0-75.0% compared to ~ 10.0-17.0% in men in the first quartiles (p < 0.001). The sensitivity and specificity of the three cardiometabolic indices in predicting TT < 12 nmol/l were significantly higher concerning BMI, waist circumference, lipid profile and HbA1c. Cut off values of VAI ≥ 3.985, TyG ≥ 4.925, and LAP ≥ 51.645 predict hypogonadism with good sensitivity and specificity. CONCLUSION: This is the first study evaluating the association of VAI, TyG, and LAP with hypogonadism in men with type 2 diabetes. Alterations in these indices should direct the patients to andrological evaluation.

Glycemic control after switching to faster aspart in adults with type 1 diabetes.

AIMS: Post-prandial hyperglycemia remains an unmet need in the management of type 1 diabetes (T1D). In randomized trials, faster insulin aspart (FIA) showed modest but significant reductions of glycemic spikes after meals. Whether such benefit is evident in routine clinical practice is unclear. METHODS: We analyzed data of patients with T1D at the time they switched from a prior bolus insulin to FIA and at the first available follow-up. The primary endpoint was the change in the time spent in hyperglycemia > 250 mg/dl during daytime from flash glucose monitoring (FGM). Secondary outcomes included the change in HbA1c, body weight, insulin dose and other FGM metrics. RESULTS: We included 117 patients with T1D on multiple daily injections who switched to FIA, 57 of whom had data from FGM. Patients were 41-year-old, 51.3% men, with 19.3 years diabetes duration and a baseline HbA1c of 7.7% (60 mmol/mol). Mean observation time was 4.3 months. After switching to FIA, HbA1c declined by 0.1% (1 mmol/mol) only in patients with baseline HbA1c > 7.0% (53 mmol/mol). Time spent in hyperglycemia > 250 mg/dl during daytime was significantly reduced from 14.8 to 11.9% (p = 0.006). Time in range improved from 48.3 to 51.0% (p = 0.028). Results were consistent across various patient characteristics. CONCLUSIONS: Under routine care, patients with T1D who switched to FIA experienced a reduction in the time spent in hyperglycemia > 250 mg/dl during daytime and an increase in time in range. These improvements may be due to better control of post-prandial hyperglycemia, as observed in trials.

A novel MRPS34 gene mutation with combined OXPHOS deficiency in an adult patient with Leigh syndrome.

We report a novel pathogenic variant (c.223G > C; p.Gly75Arg) in the gene encoding the small mitoribosomal subunit protein mS34 in a long-surviving patient with Leigh Syndrome who was genetically diagnosed at age 34 years. The patient presented with delayed motor milestones and a stepwise motor deterioration during life, along with brain MRI alterations involving the subcortical white matter, deep grey nuclei and in particular the internal globi pallidi, that appeared calcified on CT scan. The novel variant is associated with a reduction of mS34 protein levels and of the OXPHOS complex I and IV subunits in peripheral blood mononuclear cells of the case. This study expands the number of variants that, by affecting the stability of the mitoribosome, may cause an OXPHOS deficiency in Leigh Syndrome and reports, for the first time, an unusual long survival in a patient with a homozygous MRPS34 pathogenic variant.

Implantable and transcutaneous continuous glucose monitoring system: a randomized cross over trial comparing accuracy, efficacy and acceptance.

AIM: To compare accuracy, efficacy and acceptance of implantable and transcutaneous continuous glucose monitoring (CGM) systems. METHODS: In a randomized crossover trial we compared 12 weeks with Eversense implantable sensor (EVS) and 12 weeks with Dexcom G5 transcutaneous sensor (DG5) in terms of accuracy, evaluated as Mean Absolute Relative Difference (MARD) vs capillary glucose (SMBG), time of CGM use, adverse events, efficacy (as HbA1c, time in range, time above and below range) and psychological outcomes evaluated with Diabetes Treatment Satisfaction Questionnaire (DTSQ), Glucose Monitoring Satisfaction Survey (GMSS), Hypoglycemia Fear Survey (HFS2), Diabetes Distress Scale (DDS). RESULTS: 16 subjects (13 males, 48.8 ± 10.1 years, HbA1c 55.8 ± 7.9 mmol/mol, mean ± SD) completed the study. DG5 was used more than EVS [percentage of use 95.7 ± 3.6% vs 93.5 ± 4.3% (p = 0.02)]. MARD was better with EVS (12.2 ± 11.5% vs. 13.1 ± 14.7%, p< 0.001). No differences were found in HbA1c. While using EVS time spent in range increased and time spent in hyperglycemia decreased, but these data were not confirmed by analysis of retrofitted data based on SMBG values. EVS reduced perceived distress, without significant changes in other psychological outcomes. CONCLUSIONS: CGM features may affect glycemic control and device acceptance.

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.

Similar glycaemic control and risk of hypoglycaemia with patient- versus physician-managed titration of insulin glargine 300 U/mL across subgroups of patients with T2DM: a post hoc analysis of ITAS.

AIMS: The Italian Titration Approach Study (ITAS) demonstrated comparable HbA1c reductions and similarly low hypoglycaemia risk at 6 months in poorly controlled, insulin-naïve adults with T2DM who initiated self- or physician-titrated insulin glargine 300 U/mL (Gla-300) in the absence of sulphonylurea/glinide. The association of patient characteristics with glycaemic and hypoglycaemic outcomes was assessed. METHODS: This post hoc analysis investigated whether baseline patient characteristics and previous antihyperglycaemic drugs were associated with HbA1c change and hypoglycaemia risk in patient- versus physician-managed Gla-300 titration. RESULTS: HbA1c change, incidence of hypoglycaemia (any type) and nocturnal rates were comparable between patient- and physician-managed arms in all subgroups. Hypoglycaemia rates across subgroups (0.03 to 3.52 events per patient-year) were generally as low as observed in the full ITAS population. Small increases in rates of 00:00-pre-breakfast and anytime hypoglycaemia were observed in the ≤ 10-year diabetes duration subgroup in the patient- versus physician-managed arm (heterogeneity of effect; p < 0.05). CONCLUSIONS: Comparably fair glycaemic control and similarly low hypoglycaemia risk were achieved in almost all patient subgroups with patient- versus physician-led Gla-300 titration. These results reinforce efficacy and safety of Gla-300 self-titration across a range of phenotypes of insulin-naïve people with T2DM. CLINICAL TRIAL REGISTRATION: EudraCT 2015-001167-39.

Disentangling conflicting evidence on DPP-4 inhibitors and outcomes of COVID-19: narrative review and meta-analysis.

BACKGROUND: The infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread all over the world, becoming pandemic. Several studies have shown that diabetes mellitus (DM) is an independent risk factor that increases mortality and other adverse outcomes of coronavirus disease-19 (COVID-19). Studies have suggested that SARS-CoV-2 may bind dipeptidyl peptidase-4 (DPP4) for entering cells of the respiratory tract. Besides, DPP4 takes part in immune system regulation. Thus, DPP-4 inhibitors (DPP4i) may play a role against COVID-19. METHODS: We focused on the impact of DPP4i treatment on COVID-19-related outcomes in people with DM. For this purpose, we conducted a systematic review and meta-analysis to summarize the existing evidence on this topic. RESULTS: Retrospective observational studies provide inconsistent results on the association between use of DPP4i and outcomes of COVID-19. While two studies reported significantly lower mortality rates among patients with DM who received DPP4i versus those who did not, a series of other studies showed no effect of DPP4i or even worse outcomes. A meta-analysis of 7 studies yielded a neutral estimate of the risk ratio of COVID-19-related mortality among users of DPP4i (0.81; 95% CI 0.57-1.15). CONCLUSION: In the absence of randomized controlled trials, observational research available so far provides inconclusive results and insufficient evidence to recommend use of DPP4i against COVID-19.

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

AIM: 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. METHODS: We collected data from 46 diabetes clinics (n = 281,381 T2D patients), extracted data to calculate HSI and validated it against ultrasound-detected hepatic steatosis. We then examined changes in HSI among patients with a follow-up visit within 1 year after initiating newer GLMs. RESULTS: MAFLD (defined by HSI > 36, i.e., a high probability of steatosis) was present in 76.3% of the 78,895 included patients, while only 2.7% had HSI < 30 (low probability of steatosis). After age- and sex-adjusting, higher HSI was associated with higher prevalence of chronic kidney disease (odds ratio 1.35; 95%CI 1.22-1.51) and macroangiopathy (odds ratio 1.18; 95%CI 1.07-1.30). Among 2,179 subjects in the validation cohort, the prevalence of MAFLD was 67.8% and was greater in those with high HSI. Performance of HSI for ultrasound-detected MAFLD was moderate (AUROC 0.70), yet steatosis prevalence was > threefold higher among subjects with HSI > 36 than among those with HSI < 30. Notably, HSI declined significantly ~ 6 months after initiation of dapagliflozin or incretin-based therapies, but not gliclazide. CONCLUSION: About three quarters of patients with T2D have HSI values suggestive of MAFLD, a condition associated with macroangiopathy and nephropathy. Treatment with dapagliflozin or incretin therapies might improve MAFLD in T2D.

Effects of glucose variability on hematopoietic stem/progenitor cells in patients with type 1 diabetes.

BACKGROUND AND PURPOSE: Diabetes reduces the levels of hematopoietic stem/progenitor cells (HSPCs), which can contribute to organ and tissue homeostasis. Among patients with diabetes, lower HSPC levels predict the development or worsening of micro- and macro-angiopathy. High glucose variability is also associated with diabetic complications and we have previously shown that acute hypoglycaemia can stimulate stem/progenitor cells. Thus, we evaluated the relationship between glucose variability or time in hypoglycaemia and HSPCs in patients with type 1 diabetes (T1D). METHODS: Patients with T1D were compared to healthy subjects. HSPCs (CD34+, CD133+, CD34+CD133+, CD34 + CD45dim) were quantified by flow cytometry. Using flash glucose monitoring system for 90 days, we calculated several measures of glucose variability and time in hypoglycaemia. RESULTS: Forty-four patients with T1D and 44 healthy subjects were enrolled. Compared to healthy controls, T1D patients had significantly lower levels of HSPCs and duration of diabetes was inversely correlated with HSPC levels. Significant direct correlations were found between HSPC levels and the coefficient of variation of glucose levels or time in hypoglycaemia, which were stronger in patients with short-term than in those with long-standing diabetes. CONCLUSION: This study confirms the pauperization of HSPCs in T1D patients and demonstrates a potential HSPC-stimulatory effect of hypoglycaemia, which mitigates with long-lasting diabetes. These data are consistent with a model whereby disease chronicity progressively blunts the release of HSPCs in response to adrenergic triggers, like hypoglycaemic events.

Assessment of simple strategies for identifying undiagnosed diabetes and prediabetes in the general population.

BACKGROUND AND AIMS: The rising tide of diabetes mellitus (DM) and prediabetes (PDM) is urgently calling for strategies easily applicable to anticipate diagnosis. We assessed the effectiveness of random capillary blood glucose (RCBG), administration of a validated DM risk questionnaire, or the combination of both. MATERIALS AND METHODS: RCBG measurement and/or questionnaire administration were offered to all individuals presenting at gazebos organized during the World Diabetes Day or similar public initiatives on diabetes awareness. Subjects with suspicious DM or PDM were invited to the Diabetes Center (DC) for laboratory confirmation (fasting plasma glucose and HbA1c). RESULTS: Among 8563 individuals without known diabetes undergoing RCBG measurement, 341 (4%) had suspicious values. Diagnosis of DM was confirmed in 36 (41.9%) of the 86 subjects who came to the DC and PDM was found in 40 (46.5%). Among 3351 subjects to whom the questionnaire was administered, 480 (14.3%) had suspicious scores. Diagnosis of DM was confirmed in 40 (10.1%) of the 397 who came to the DC and PDM was found in 214 (53.9%). These 3351 subjects also had RCBG measurement and 30 out of them had both tests positive. Among them, 27 subjects came to DC and DM was diagnosed in 17 (63.0%) and PDM was found in 9 (33.3%). CONCLUSIONS: These data suggest that RCBG definitely outperforms the questionnaire to identify unknown DM and PDM. RCBG measurement, with questionnaire as an adjunctive tool, appears to be a simple, fast, and feasible opportunistic strategy in detecting undiagnosed DM and PDM.

SARS CoV2 infection in a young subject affected by arginosuccinate synthase deficiency: A case report of epilepsy worsening.

We describe a case of a 21 years old woman affected by Citrullinemia type 1- Arginosuccinate Synthase deficiency (ASSD)-who underwent a SARS CoV2 infection during the first phase of pandemic burst in Italy. She had no symptoms of infection nor a metabolic crisis. After recovery from SARS CoV2, she experienced a worsening in their epilepsy despite therapy, with one/two crisis a week.

Incidence of heart failure in patients with type 1 diabetes: a systematic review of observational studies.

BACKGROUND: Heart failure (HF) is considered an important contributor to cardiovascular morbidity and mortality in diabetes mellitus. However, a precise identification of hyperglycemia as contributor for HF is missing. OBJECTIVES: We performed a review and a meta-regression of the available observational studies on the incidence of HF in type 1 diabetes (T1D). DATA SOURCE AND ANALYSIS: We conducted a systematic search of the literature on the incidence of HF in patients with T1D identifying suitable studies published between January 1970 and June 2018 using the following search string: "type 1 diabetes" AND, "heart failure" OR "cardiac failure" OR "congestive heart failure" AND "incidence" NOT "type 2 diabetes" OR "diabetes type 2". Six observational studies were included. A random effect meta-regression model has been estimated to evaluate the incidence rate ratio (IRR) of HF in T1D compared to healthy controls. RESULTS: The mean ± SD age of patients with T1D was 42 ± 11 years, the mean HbA1c was 8.4 ± 0.3%, and average follow-up was 11 ± 3 years. The age-adjusted model shows an incidence rate ratio (IRR) effect of 3.18 (p < 0.001), in correspondence of the mean age at enrollment of studies involved in the analysis. A negative correlation was observed between IRR and average age. CONCLUSIONS: This review shows that the incidence rate of HF is three times higher in patients with T1D than in controls. A careful surveillance of the risk factors for this condition should be included, since the onset of T1D may be important to reduce HF risk in these patients.

Predictors of early discontinuation of dapagliflozin versus other glucose-lowering medications: a retrospective multicenter real-world study.

BACKGROUND AND AIMS: In routine clinical practice, early discontinuation of newly initiated glucose-lowering medications (GLM) is relatively common. We herein evaluated if the clinical characteristics associated with early discontinuation of dapagliflozin were different from those associated with early discontinuation of other GLM. METHODS: The DARWIN-T2D was a multicenter retrospective study conducted at diabetes specialist outpatient clinics in Italy. We included 2484 patients who were initiated on dapagliflozin in 2015-2016 and 14,801 patients who were initiated on other GLM (DPP-4 inhibitors, GLP-1 receptor agonists, or gliclazide) in the same period. After excluding patients who had not (yet) returned to follow-up, we compared the characteristics of patients who persisted on drug versus those who were no longer on drug at the first available follow-up after at least 3 months. RESULTS: As compared to those who persisted on drug, patients who discontinued dapagliflozin (51.7%) were more often female, had higher baseline fasting plasma glucose (FPG), HbA1c, and eGFR, and less common use of metformin. Upon multiple regression, higher HbA1c, higher eGFR, and lower metformin use remained independently associated with early discontinuation. Among patients who had been initiated on other GLM, 41.7% discontinued. Variables independently associated with discontinuation were older age, longer diabetes duration, higher HbA1c, eGFR, and albumin excretion, more common use of insulin and less metformin. CONCLUSION: In routine clinical practice, all variables associated with dapagliflozin discontinuation were also associated with discontinuation of other GLM. Thus, despite a distinctive mechanism of action and a peculiar tolerability profile, no specific predictor of dapagliflozin discontinuation was detected.