PERsistent Sitagliptin treatment & Outcomes (PERS&O 2.0) study, long-term results: a real-world observation on DPP4-inhibitor effectiveness.

INTRODUCTION: Sitagliptin is a dipeptidyl peptidase 4 inhibitor for the treatment of type 2 diabetes (T2D). Limited real-world data on its effectiveness and safety are available from an Italian population. RESEARCH DESIGN AND METHODS: We evaluated long-term clinical data from the single-arm PERsistent Sitagliptin Treatment & Outcomes (PERS&O) study, which collected information on 440 patients with TD2 (275 men, 165 women; mean age 64.1 years; disease median duration: 12 years) treated with sitagliptin 'add-on'. For each patient, we estimated the 10-year cardiovascular (CV) risk using the UK Prospective Diabetes Study (UKPDS) Risk Engine (RE). Drug survival was evaluated using Kaplan-Meier survival curves; repeated measures mixed effects models were used to evaluate the evolution of glycated hemoglobin (HbA1c) and CV risk during sitagliptin treatment. RESULTS: At baseline, most patients were overweight or obese (median body mass index (BMI) (kg/m2) 30.2); median HbA1c was 8.4%; median fasting plasma glucose: 172 mg/dL; median UKPDS RE score: 24.8%, being higher in men (median 30.2%) than in women (median 17.0%) as expected. Median follow-up from starting sitagliptin treatment was 5.6 years. From Kaplan-Meier curves, the estimated median drug survival was 32.8 months when considering discontinuation for any cause and 58.4 months when considering discontinuation for loss of efficacy. A significant improvement in HbA1c was evident during treatment with sitagliptin (p<0.01): the reduction was rapid (median HbA1c after 4-6 months: 7.5%) and continued at longer follow-up. When comparing patients treated with sitagliptin versus those stopping sitagliptin and switching to another antihyperglycemic drug, we detected a significant difference in the evolution of HbA1c in favor of patients who continued sitagliptin treatment. The UKPDS RE score at 10 years and the BMI significantly improved during treatment with sitagliptin (p<0.001). Adverse events were relatively uncommon. CONCLUSION: Patients with T2D treated with sitagliptin achieved an improvement in metabolic control and a reduction in CV risk and did not experience relevant adverse events.

ANDREW: A Multicenter, Prospective, Observational Study in Patients with Type 2 Diabetes on Persistent Treatment with Dulaglutide.

INTRODUCTION: Dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), became available in Italy in April 2016. The aim of ANDREW (Active Notes on Dulaglutide in the REal World), a multicenter, prospective, observational study, was to evaluate glycemic control and weight (co-primary outcomes) for up to 24 months in the real-life setting in consecutive outpatients with type 2 diabetes (T2D) who initiated dulaglutide. Co-secondary outcomes were durability of treatment effects on both glycated hemoglobin (HbA1c) and body weight. METHODS: Overall, 1584 subjects (696 women, 888 men) with T2D (mean age [± standard deviation] 61.7 ± 10.2 years; mean T2D duration 9.9 ± 6.9 years) were treated with dulaglutide (0.75 or 1.5 mg once weekly) between April 2016 and December 2019. RESULTS: A total of 1130 patients completed 12 months of follow-up, while 170 patients interrupted treatment before the 12-month endpoint. At 12 months, average HbA1c and average fasting plasma glucose (FPG) were significantly lower compared to baseline levels (- 10 mmol/mol and - 24.9 mg/dL, respectively), as were body weight (- 3.4 kg) and waist circumference (- 3.3 cm) values (all p < 0.0001). Among subjects that completed 24 months of follow-up (n = 270), the rapid decline in HbA1c and FPG values in the first 12 months was followed by stabilization in the following 12 months (p value for 12-24 months trend: 0.4 and 0.6, respectively). CONCLUSIONS: Dulaglutide is an effective drug for the treatment of T2D that is administered once weekly using a simple auto-injector device. Real-life data confirm the observations in randomized controlled trials that persistent treatment with dulaglutide may help patients with T2D achieve an improvement in some metabolic features and in body weight. It is important that the benefits of therapy with dulaglutide, i.e., the effects of the "glycemic" and the so-called "extra-glycemic" actions of GLP-1RAs, are supported by diabetes care teams emphasizing the need for patients to maintain a healthy lifestyle.

Insulin Management for Type 1 Diabetic Patients During Social Alcohol Consumption: The SPRITZ Study.

BACKGROUND: There is no data available on the best insulin treatment to counteract the effects of glucose excursions due to a moderate alcohol intake associated with portions of slight fat and protein-containing food, as often the case during social happenings or "happy hours". INTRODUCTION: This study analyzes the glycemic control and quality of life in 8 adult type 1 diabetic (T1D) patients on insulin-pump therapy which were invited to consume a traditional Italian aperitif ("Spritz" and chips). METHODS: Patients consumed Spritz aperitif twice: using their habitual bolus, based on carbohydrates (CHO) counting (V1), or with a personalized, advanced bolus (V2) calculated from insulin/Kcal derived from Fats and Proteins (FPU). Post-prandial glucose was continuously monitored; glucose incremental areas (iAUC), glucose peak and time to peak, and estimated change from V1 to V2 from repeated- measures models were computed. Each patient fulfilled validated questionnaires on quality of life, knowledge about diabetes and CHO counting. RESULTS: After the educational program, a reduced iAUC (0-80 min: -306, p=ns; 40-80 min: -400, p=0.07) due to greater (p=0.03) and prolonged double-wave insulin boluses was observed. Blood glucose peak and time to peak were also reduced. Moreover, improvements in the psycho-affective dimension, as well as in the alimentary knowledge were detected. CONCLUSION: Therefore, a personalized educational program on CHO + FPU counting together with insulin bolus management can improve glycemic control during social consumption of alcohol, with positive reflections on the psycho-affective dimension. Further studies are mandatory to confirm such preliminary results.

PERS&O (PERsistent Sitagliptin treatment & Outcomes): observational retrospective study on cardiovascular risk evolution in patients with type 2 diabetes on persistent sitagliptin treatment.

OBJECTIVES: The UK Prospective Diabetes Study (UKPDS) Risk Engine (RE) provides the best risk estimates available for people with type 2 diabetes (T2D), so it was applied to patients on persistent sitagliptin treatment. DESIGN: A 'real-world' retrospective, observational, single-center study. SETTING: The study was performed in a general hospital in Northern Italy in order: (1) to validate UKPDS RE in a cohort of Italian participants with T2D without prespecified diabetes duration, with/without cardiovascular (CV) disease, treated with sitagliptin; (2) to confirm CV risk gender difference; (3) to evaluate the effect on metabolic control and on CV risk evolution obtained by 'add-on' persistent sitagliptin treatment. PARTICIPANTS: Sitagliptin 100 mg once a day was taken by 462 participants with T2D: 170 of them (males: 106; age: 63.6±8.8; T2D duration: 11.58±7.33; females: 64; age: 65.6±7.95; T2D duration 13.5±7.9) were treated for 48 months with the same dosage. INTERVENTIONS: An analysis of normality was performed both for continuous, and for groups variables on UKPDS RE percentage values, defining the requirement of a base log10 transformation to normalize risk factor values for analysis validation. RESULTS: The evaluation of CV risk evolution by gender (t-test) confirmed the expected statistical difference (p<0.0001). Sitagliptin obtained significant results after 12 months, and at the end of the observation, both on metabolic control (expressed by glycated hemoglobin) and on UKPDS RE. Analysis of variance test revealed a significant effect on CV risk after 12 months (p=0.003), and after 48 months (p=0.04). A bivariate correlation analysis revealed a correlation index (r)=0.2 between the two variables (p<0.05). CONCLUSIONS: These 'real-world' data obtained applying UKPDS RE may reflect patients' and clinicians' interest in realizing individual CV risk, and its evolution. Sitagliptin-persistent treatment for a medium-long period obtained an improvement on metabolic control, as well as a reduction on CV risk.