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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Dapagliflozin has been demonstrated to improve glycemic control, blood pressure, and body weight in type 2 diabetes mellitus (T2D); indeed, it can also reduce the risk of progression to renal ...failure, of hospitalization for heart failure and of cardiovascular death. We aim to investigate the acute effect of Dapagliflozin on kidney function in the common clinical practice in T2D. This is a study including 1402 patients with T2D recruited from 11 centers in Lombardia, Italy, who were evaluated at baseline and after 6 months of treatment with Dapagliflozin 10 mg per day. The primary outcome of the study was the change in HbA1c, while the secondary outcomes were modification of weight, BMI, systolic and diastolic pressure, creatinine, eGFR and albuminuria status. After 24 weeks of treatment with Dapagliflozin, a reduction in Hb1Ac was observed (−0.6 ± 1.8%) as well as in BMI (−1.5 ± 5.2 kg/m2). Statistically significant changes were also found for systolic and diastolic blood pressure, cholesterol and triglycerides. Interestingly, a statistically significant acute improvement of kidney function was evident. Our analyses confirm the beneficial effects of dapagliflozin after 6 months of therapy, with improvements of glycemic and lipid profiles, blood pressure, BMI. Finally, an acute positive effect on albuminuria and KIDGO classes was observed during a 6 months treatment with dapagliflozin in patients with T2D.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aim
To describe the development of the AWARE App, a novel web application for the rapid assessment of cardiovascular risk in Type 2 Diabetes Mellitus (T2DM) patients. We also tested the feasibility ...of using this App in clinical practice.
Methods
Based on 2019 European Society of Cardiology/European Association for the Study of Diabetes criteria for cardiovascular risk stratification in T2DM, the AWARE App classifies patients into very high (VH
CVR
), high (H
CVR
) and moderate (M
CVR
) cardiovascular risk categories. In this retrospective clinical study, we employed the App to assess the cardiovascular risk of T2DM patients, while also collecting data about current glycaemic control and pharmacological treatment.
Results
2243 T2DM consecutive patients were evaluated. 72.2% of the patients were VH
CVR
, 8.9% were H
CVR
, 0.8% were M
CVR
while 18.2% did not fit into any of the risk categories and were classified as “moderate-to-high” (MH
CVR
). Compared with the other groups, patients with VH
CVD
were more frequently ≥ 65 years old (68.9%), with a longer disease duration (≥ 10 years 56.8%), a history of cardiovascular disease (41.4%), organ damage (35.5%) and a higher numbers of cardiovascular risk factors. Patients with MH
CVD
generally had disease duration < 10 years (96%), younger age (50–60 years 55%), no history of cardiovascular disease, no organ damage, and 1–2 cardiovascular risk factors (89%). Novel drugs such as Glucagon Like Peptyde 1 Receptor Agonists or Sodium-Glucose Linked Transporter 2 inhibitors were prescribed only to 26.3% of the patients with VH
CVR
and to 24.7% of those with H
CVR
. Glycaemic control was unsatisfactory in this patients population (HbA1c 7.5 ± 3.4% 58.7 ± 13.4 mmol/mol).
Conclusions
The AWARE App proved to be a practical tool for cardiovascular risk stratification of T2DM patients in real-world clinical practice.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The 2019 ESC-EASD guidelines provide recommendations for CV risk assessment and medical treatment in diabetic patients. Three CV risk categories were originally defined: 1) very high risk, 2) high ...risk and 3) moderate risk according to the presence of CVD, other target organ damage (proteinuria, renal impairment defined as eGFR ≥ 30 mL/min/1.73 m2, left ventricular hypertrophy, retinopathy), duration of disease, age, risk factors (hypertension, dyslipidemia, smoking, obesity). In very high risk CV category SGLT2-I and GLP1-RA were identify as treatment of choice. Based on these criteria, we developed the web APP “AWARE”, an application software which runs on a web server and is accessed via internet browser. From November 10th 2020 to January 10th 2021 we employed AWARE as a tool to assess CV risk of 650 type 2 diabetes patients in clinical practice. The APP was implemented with additional features such as HbA1c and therapy. Of the 650 subjects examined, 430 were very high risk (66%), 73 (11,2%) high risk, 5 (0,8%) at moderate risk while 145 patients (22%) didn’t match with any of these categories. We allocated these patients into an additional “undetermined risk” category. Median HbA1c in all subjects was 7.2±1.14 (7,3±1.15% in very high risk category, 7.2±1.15% in high risk category, 6,2±0.41% in moderate risk and 6.9±1.12% in “undetermined” risk). In the very high risk category CVD was present in 166 subject (38%), duration of disease>10 aa in 238 subjects (55%), proteinuria in 53 subjects (12%) (p=0.000 vs. all other categories). Either SGLT2-I or GLP1-RA were prescribed in 30% of patients in the very high risk category. The APP “AWARE” in useful to identify CV risk in diabetic. The classification according to the criteria of 2019 ESC/EASD guidelines does not includes 22% of patients in clinical practice. Around 70% of patients in the very high CV risk category are not treated with the optimal drug therapy suggested by the 2019 ESC/EASD guidelines.
Disclosure
C. C. Berra: None. R. Manfrini: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Mundipharma International, Novo Nordisk, Sanofi. R. Ghelardi: None. P. M. Bollati: None. L. Bucciarelli: None. M. Mirani: None. M. Muratori: None. F. Folli: None. Aware study group: n/a.
Elevated cell Na(+)-H(+) exchange (NHE) activity characterizes diabetic nephropathy (DN), but the mechanisms of this abnormality are unclear. Recent evidence suggests that NHE and the Ca(2+) pump ...share similar regulatory pathways, but whether abnormalities in Ca(2+) metabolism characterize DN is not known. We investigated Ca(2+) efflux rates, NHE activity, cytosolic Ca(2+) (Ca(2+)(i)) concentrations, and intracellular pH (pH(i)) in human skin fibroblasts from 20 patients with type 1 (insulin-dependent) diabetes and nephropathy; 20 patients with diabetes with normoalbuminuria matched for age, sex, and duration of diabetes; and 10 individuals without diabetes. Ca(2+) pump-mediated Ca(2+) efflux was significantly lower in patients with nephropathy than in patients with normoalbuminuria and individuals without diabetes (0.074 +/- 0.01 versus 0.115 +/- 0.01 versus 0.131 +/- 0.02 nmol.mg(protein)(-1).min(-1); analysis of variance ANOVA, P = 0.015). Elevated maximal velocity of the Na(+)-H(+) exchanger was confirmed in fibroblasts from patients with nephropathy (14.4 +/- 1.2 versus 7.1 +/- 0.7 versus 8.0 +/- 1.2 mmol H(+).l cell(-1).min(-1); ANOVA, P < 0.0001). A reverse correlation between Ca(2+) pump activity and NHE rates could be shown. Adjustment for glycated hemoglobin and plasma lipid levels did not affect these findings. Finally, Ca(2+)(i) concentrations and pH(i) were normal in all patients. Low Ca(2+) pump activity is a concomitant event of elevated NHE rates in DN; the molecular dysfunction(s) underlying these abnormalities remains to be established.
