Effects of GLP-1RAs on cardiovascular outcomes in patients with type 2 diabetes mellitus: review of real-world data on target populations from diabetes registry in Russian Federation

RATIONALE. Over the past 20 years the prevalence of type 2 diabetes in Russia has more than doubled and reached 4.43 million people in 2020, while the growth rate keeps increasing. Most patients with T2DM are at a higher risk of developing major adverse cardiovascular events (MACE) associated with significant mortality. There is a strong evidence base that the drugs belonging to GLP-1RA class contribute to reducing the risk of cardiovascular events and renal outcomes. At the same time, the current prescribing rates of these treatments in Russia are quite low - only about 0.1% of patients are prescribed GLP-1RAs, according to Diabetes Registry data.AIM. Review the results of several randomized clinical trials (RCTs) concerning effects of GLP-1RA treatments on prevention of primary and secondary cardiovascular events and estimate the number of diabetic target population.MATERIALS AND METHODS. We examined the data from clinical trials on GLP-1RA treatments registered in Russia and used in routine clinical practice (ELIXA, EXSCEL, LEADER, SUSTAIN-6 and REWIND) and data from two meta-analyzes published as of December 1, 2020. The task was to evaluate the inclusion criteria, patient profile, and the clinical efficacy and safety profiles of  the studied therapies. Also, the analysis of clinical information from the Diabetes Registry (DR) was performed to estimate the number of target T2DM patients meeting RCTs inclusion criteria that could benefit from prescribing of GLP-1RAs.RESULTS. The reviewed clinical trials demonstrated a statistically significant reduction (p <0.05) in the risk of serious cardiovascular events in patients treated with Liraglutide [RR 0.87 (95% CI, 0.78-0.97)], Semagltuide [OP 0.74 (95% CI 0.58-0.95)] and Dulaglutide [RR 0.88 (95% CI 0.79-0.99)]. Meta-analyzes utilizing data from 6 RCTs with the total number of 56,004 T2DM patients, also, confirmed a statistically significant reduction in the risk of developing MACE (by 12%) in the studied population, and a 17% reduction in the risk of combined renal outcomes [RR 0.83 (95% CI 0.78-0.89), p <0.0001]. The DR patient population that met the RCTs inclusion criteria amounted to 538.6 thous. subjects in case of REWIND and 432.4 thous. in case of LEADER and SUSTAIN-6. The key differences between FDR patients and patients engaged in RCTs included gender and age characteristics. The DR patients were generally older and the bulk of them were women, which has to do with overall Russian demographic trends. The proportion of DR patients with established CVD was 26%, which closely matched the profile of patients from REWIND study (31.5%). According to DR data, the number of patients in whom the treatment was intensified following prescription of basal insulin was 7612 per year, which is close to a potential cohort eligible for alternative treatment with GLP-1RAs.CONCLUSION. All the drugs belonging to GLP-1RA class are clinically effective in reducing the risk of cardiovascular and renal outcomes, while demonstrating a favorable safety profile including with respect to lower risk of developing hypoglycemia. The decreased risk of complications was recorded both in patients with existing cardiovascular risks and patients with established CVD. Of all GLP-1RA treatments available in Russia at this point, the greatest clinical effectiveness is achieved by Liraglutide, Semaglutide and Dulaglutide. The estimated patient population from DR, meeting RCTs inclusion criteria and matching RCTs patient profile was over 500, 000 people with the largest number of patients meeting the REWIND criteria. The target population of patients with T2DM who may potentially benefit from the administration of GLP-1RAs is over 500, 000 people. Out of that number at least 7.5 thousand are patients, whose treatment is intensified following prescription of basal insulin (with an aim of improving glycemic control, but without consideration of cardiovascular risks).Currently, if we take the real world clinical setting in Russia, the number of patients receiving GLP-1RA treatments is substantially lower than the estimated figures (less than 1%), which requires reconsideration of the approach toward their prescribing as is recommended by state-of-the-art clinical guidelines prioritizing prevention of cardiovascular risks

The role of renin-angiotensin system and angiotensin-converting enzyme 2 (ACE2) in the development and course of viral infection COVID-19 in patients with diabetes mellitus

The role of renin-angiotensin system (RAS) in general and angiotensin-converting enzyme 2 (ACE2) in particular in the  pathogenesis and course of viral infection caused by SARS-CoV-2 (COVID-19) is of particular interest. This is due not only to the fact that ACE2 is a receptor for the virus the target cells. RAS hyperactivation in patients with arterial hypertension, cardiovascular disease and diabetes mellitus, is considered one of the most important factors for a more severe infection in persons with concomitant pathology. In addition, the effects of PAS blockage with angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARBs) remains one of the most discussed topics in the literature on COVID-19. This review presents the data on the interaction between the virus and the main components of RAS and the factors influencing their expression level, the impact of ACE ­inhibitors and ARBs therapy on the disease outcome, and presents the perspectives of the treatment with recombinant ACE 2

Epidemiological characteristics of diabetes mellitus in the Russian Federation: clinical and statistical analysis according to the Federal diabetes register data of 01.01.2021

BACKGROUND. One of the priority directions in the development of the health care system is to reduce the medical and social damage caused by the increase in the prevalence of diabetes mellitus (DM). From this point of view, the development of a diabetes register is very important as the main information and analytical platform for clinical and epidemiological monitoring of diabetes in the Russian Federation (RF).AIMS. The aim of our study was to analyze a dynamic (2016–2020) of the epidemiological characteristics of diabetes mellitus in the Russian Federation (prevalence, morbidity, mortality), the prevalence of complications, the level of HbA1c and the dynamics of the structure of glucose-lowering therapy (GLT) according to the Federal Diabetes Register (FDR).MATERIALS AND METHODs. The database of FRD (http://diaregistry.ru) 84 regions of the RF. The data are presented in dynamics 2016→2020.RESULTS. The total number of DM patients in the RF as of 01.01.2021 was 4,799,552 (3.23% of the population), including: Type 1 (T1) — 5.5% (265.4 ths) , T2 — 92.5% (4.43 million), other DM types — 2.0% (99.3 ths). The dynamics of prevalence was 168.7→180.9/100 ths people with T1, and 2709 → 3022/100 ths people with T2; morbidity in T1 10.5→7.7/100 ths population, in T2 219.6→154.2/100 ths population. Age and sex characteristics: the proportion of men in T1 — 54%, in T2 — 30%; the max proportion of patients with T1 at the age of 30–39 years, T2 65–69 years. Mortality: T1 3.0 → 2.7/100 ths population, T2 87.7→93.9/100 ths of the population, the main cause of death was cardiovascular: in T1 38,1% cases, in T2 — 52,0%. Life expectancy (average age of death of patients): T1 was 53.2years, the dynamics in males 50.7 → 50.5years, ­females 58.7→55.2years; in T2 — 73.5 years, males 70.2→70.1years, females 75.7→75.4 years. The dynamic of DM duration until the death: in T1 17.4→19.0 years; in T2 11→11.4 years. The incidence of diabetic complications in T1 and T2 patients: neuropathy 43.3% and 24.4%, nephropathy (CKD) 25.9% and 18.4%, retinopathy 31.7% and 13.5%, respectively. The ­proportion of ­patients with HbA1c <7%: in T1 32.3%→36.9%, in T2 51.9%→52.1%, with HbA1c ≥ 9.0% in T1 23.1%→18.7% , in T2 8.9%→8.0%. The structure GLT in T2 patients: glucose lowering medications (GLM) — 76.2% (monotherapy — 44.1%; ­combination of  2 GLM — 28.9%, 3 GLM — 3.2%), insulin therapy in 18,8%, without drug therapy in 4.9%.CONCLUSIONS. The performed analysis demonstrates the importance of dynamic assessment of epidemiological characteristics and monitoring of clinical data on patients with diabetes through a registry for assessing the quality of diabetes care and the prospects for its development

Renal effects of glucagon-like peptide receptor agonists in patients with type 1 diabetes mellitus

The purpose of our study is to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1R agonists) on early markers of kidney damage in patients with type 1 diabetes mellitus (DM). Materials and methods. The study included 27 patients with type 1 diabetes with normo- (n=16) and microalbuminuria (n=11) on intensive insulin injection regimen with insulin analogs. Patients were divided into two groups: 15 patients continued insulin therapy throughout the follow-up period, 12 patients were given 1.2 mg GLP-1R agonist (Liraglutide) once a day in addition to the insulin therapy for 6 months. HbA1c, lipid profile, classic markers of kidney damage (albuminuria, creatinine, glomerular filtration rate); plazma (neutrophilic gelatinase-associated lipoxalin - NGAL, molecule renal damage of type 1 - KIM-1, cystatin C, osteopontin) and urinary kidney biomarkers (nephrin, podocyne, uromodulin, NGAL, KIM-1, collagen type IV, cystatin C) were evaluated prior and in dynamics at 6 months. Kidney biomarkers levels were assessed by the enzyme-linked immunosorbent assay (ELISA). Results. We observed a significant decrease in the urinary excretion of type IV collagen, cystatin C, increased uromodulin excretion and decrease in the plasma levels of osteopontin, NGAL and cystatin C in the group of combined insulin and GLP-1R agonist therapy. Conclusions. Changes in the level of sensitive kidney biomarkers indicate a possible renoprotective effect of GLP-1R agonist therapy in patients with type 1 diabetes at an early stages of kidney damage

Diabetes mellitus in the Russian Federation: dynamics of epidemiological indicators according to the Federal Register of Diabetes Mellitus for the period 2010–2022

BACKGROUND. The clinical and epidemiological characteristics of diabetes mellitus (DM) and the quality of its therapy are the key prognostic dominant that determines the organizational aspects of the diabetic service. The continuous dynamic   monitoring of DM has been carried out in the Russian Federation (RF) since 1996 through the activities of the Federal Register of Diabetes Mellitus (FDR).AIMS. The aim of our study was to analyze the epidemiological characteristics of DM in the RF (prevalence, morbidity, mortality), the prevalence diabetic of complications, the state of carbohydrate metabolism (level of HbA1c) and the dynamics of the structure of glucose-lowering therapy (GLT) according to the FDR.MATERIALS AND METHODS. The database of FRD (https://www.diaregistry.ru/), 85 regions of the RF. The data are presented as of 01.01.2023 and in dynamics for the period 2010–2022.RESULTS. The total number of DM patients in the RF as of 01.01.2023 was 4 962 762 (3.31% of the population), including: Type 1 (T1) — 5.58% (277.1 ths), T2 — 92.33% (4.58 million), other DM types —2.08% (103 ths). The dynamics of prevalence over the 13-year period (2010→2022) was 146.0→191.0/100 ths people with T1, and 2036.2→3158.8/100 ths people with T2; morbidity in T1 12.3→8.2/100 ths population, in T2 260.1→191.4/100 ths population; мortality: T1 2.1→2.4/100 ths population, T2 41.2→86.1/100 ths of the population. The main cause of death was cardiovascular: in T1 38.6% cases, in T2 — 50.9%. Life expectancy (average age of death of patients): T1 was 52.7 years, the dynamics in males 50.9 → 50.7 years, females 62.1→56.0 years; in T2 — 74.2 years, males 69.5→70.4 years, females 74.2→76.1 years. The dynamic of DM duration from onset to the death: in T1 15.4→19.9 years; in T2 11→11.4 10.2→11.8 years. The proportion of patients with laboratory-measured HbA1c <7% in the dynamics of 2010–2022: with DM1 24.4%→29%, with DM2 41.5%→42.2%, with HbA1c ≥9.0%: with DM1 29, 4% → 20.4%, with DM2 13.8 → 9.0%.The incidence of diabetic complications as of 01.01.2023 in T1 and T2 patients: neuropathy 41.3% and 23.7%, nephropathy (CKD) 22.8% and 19.1%, retinopathy 28.9% and 12.3%, respectively. The structure GLT in T2 patients as of 01.01.2023: monotherapy — 41.6%; combination of 2 GLM — 30.0%, 3 GLM — 5.8%, insulin therapy in 18.3%.CONCLUSIONS. The information-analytical system FDR is a key tool for systematizing the most important epidemiological and clinical characteristics of DM based on data from real clinical practice, which allows optimizing the algorithm of patient management and improving the quality of care for diabetes

Analysis of risk factors for COVID-19-related fatal outcome in 337991 patients with type 1 and type 2 diabetes mellitus in 2020–2022 years: Russian nationwide retrospective study

BACKGROUND: The coronavirus pandemic has had an extremely negative impact on the patients with diabetes mellitus (DM both in terms of a more severe course of COVID -19 and an increased risk of death.AIM: Analysis of risk factors for death due to COVID -19 in patients with DM type 1 and type 2 (DM1 and DM2).MATERIALS AND METHODS: Retrospective analysis of the database of the national diabetes register (NDR), which included DM patients with COVID-19 and reported virus infection outcome (recovery/or death) in 15 712 DM1 and 322 279 DM2 patients during a 2-year follow-up period (01/02/2020 to 03/04/2022) (discharge date)).RESULTS: Case fatality rate in patients with DM, who underwent COVID -19 was 17.1% (DM1–8.8%; DM2–17.5%). As a result of multivariate regression analysis of seven significant factors in DM1 and thirteen in DM2 (evaluated by univariate anlisys), a number of the most important predictors of risk for fatal outcome were identified: in DM1 these were age ≥65 years (OR =4.01, 95% CI: 1.42–11.36), presence of arterial hypertension (AH) (OR =2.72, 95% CI: 1.03 -7.16) and diabetic foot syndrome (DFS) (OR = 7.22, 95% CI: 1.98–26.29); for T2DM: age ≥ 65 years (OR =2.53, 95% CI: 1.96–3.27), male (OR =1.51, 95% CI: 1.23–1.84), duration DM ≥10 years (OR =2.01, 95% CI: 1.61–2.51), BMI ≥ 30 kg/m2 (OR =1.26, 95% CI: 1.02–1.55), ASCVD/CKD (OR =1.49, 95% CI: 1.01–2.04), history of diabetic coma (OR =12.97, 95% CI: 1.89–88.99) and presence of disability ( OR =1.40, 95% CI: 1.14–1.73). In T2DM, the type of antidiabetic therapy (ADT) prior to COVID -19 (last visit before the development of infection) had a significant impact: Insulin therapy (OR = 1.64, 95% CI: 1.30–2.07), sulfonylureas (SU) (OR =1.51, 95% CI: 1.23–1.84)); dipeptidyl peptidase-4 inhibitor (iDPP-4) therapy (OR =0.57, 95% CI: 0.39–0.83) and sodium-glucose cotransporter-2 inhibitor (iSGLT2) therapy (OR =0.64, 95% CI: 0.46–0.88). Vaccination was the most important protective factor in both types of DM: DM1 OR =0.19, 95% CI: 0.06–0.59; SD2 OR =0.20, 95% CI: 0.16–0.26.CONCLUSION: The common risk factor for fatal outcome in both DM1 and DM2 was age ≥65 years; in DM1 — history of hypertension and DFS, in DM2 — male sex, diabetes duration ≥10 years, BMI ≥30 kg/m2, history of ASCVD/CKD and diabetic coma, disability. In T2DM, significant differences in risk were observed depending on the type of ADT: insulin and SU therapy were factors that increased the risk of death, whereas therapy with iDPP-4 and iSGLT2 reduced the risk of death. Vaccination reduced the risk of death in DM1 and DM2 by 5.2 and 5-fold, respectively

Cardiovascular disease management in people with diabetes outside North America and Western Europe in 2006 and 2015

Aim: Optimal treatment of cardiovascular disease is essential to decrease mortality among people with diabetes, but information is limited on how actual treatment relates to guidelines. We analysed changes in therapeutic approaches to anti-hypertensive and lipid-lowering medications in people with Type 2 diabetes from 2006 and 2015. Methods: Summary data from clinical services in seven countries outside North America and Western Europe were collected for 39 684 people. Each site summarized individual-level data from outpatient medical records for 2006 and 2015. Data included: demographic information, blood pressure (BP), total cholesterol levels and percentage of people taking statins, anti-hypertensive medication (angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor blockers, thiazide diuretics) and antiplatelet drugs. Results: From 2006 to 2015, mean cholesterol levels decreased in six of eight sites (range: −0.5 to −0.2), whereas the proportion with BP levels > 140/90 mmHg increased in seven of eight sites. Decreases in cholesterol paralleled increases in statin use (range: 3.1 to 47.0 percentage points). Overall, utilization of anti-hypertensive medication did not change. However, there was an increase in the use of angiotensin II receptor blockers and a decrease in angiotensin-converting enzyme inhibitors. The percentage of individuals receiving calcium channel blockers and aspirin remained unchanged. Conclusions: Our findings indicate that control of cholesterol levels improved and coincided with increased use of statins. The percentage of people with BP > 140/90 mmHg was higher in 2015 than in 2006. Hypertension treatment shifted from using angiotensin-converting enzyme inhibitors to angiotensin II receptor blockers. Despite the potentially greater tolerability of angiotensin II receptor blockers, there was no associated improvement in BP levels.Centro de Endocrinología Experimental y Aplicad

Cardiovascular disease management in people with diabetes outside North America and Western Europe in 2006 and 2015

Aim: Optimal treatment of cardiovascular disease is essential to decrease mortality among people with diabetes, but information is limited on how actual treatment relates to guidelines. We analysed changes in therapeutic approaches to anti-hypertensive and lipid-lowering medications in people with Type 2 diabetes from 2006 and 2015. Methods: Summary data from clinical services in seven countries outside North America and Western Europe were collected for 39 684 people. Each site summarized individual-level data from outpatient medical records for 2006 and 2015. Data included: demographic information, blood pressure (BP), total cholesterol levels and percentage of people taking statins, anti-hypertensive medication (angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor blockers, thiazide diuretics) and antiplatelet drugs. Results: From 2006 to 2015, mean cholesterol levels decreased in six of eight sites (range: −0.5 to −0.2), whereas the proportion with BP levels > 140/90 mmHg increased in seven of eight sites. Decreases in cholesterol paralleled increases in statin use (range: 3.1 to 47.0 percentage points). Overall, utilization of anti-hypertensive medication did not change. However, there was an increase in the use of angiotensin II receptor blockers and a decrease in angiotensin-converting enzyme inhibitors. The percentage of individuals receiving calcium channel blockers and aspirin remained unchanged. Conclusions: Our findings indicate that control of cholesterol levels improved and coincided with increased use of statins. The percentage of people with BP > 140/90 mmHg was higher in 2015 than in 2006. Hypertension treatment shifted from using angiotensin-converting enzyme inhibitors to angiotensin II receptor blockers. Despite the potentially greater tolerability of angiotensin II receptor blockers, there was no associated improvement in BP levels.Centro de Endocrinología Experimental y Aplicad

Consensus position of endocrinologists and pathologists on coding causes of death in patients with diabetes mellitus (expert opinion)

Coding of the causes of death of patients with diabetes mellitus (DM) in the Russian Federation is one of the long-discussed problems, due to the comorbidity of diabetes and cardiovascular diseases (CVD) and a number of contradictions in the key regulatory documents regulating the statistics of mortality in this category of patients, which acquires particular relevance in the context of the coronavirus pandemic, due to its negative impact on the outcomes of the course of COVID-19 and mortality risks. In pursuance of the decisions of the Minutes of the meeting of the working group under the project committee of the National Project «Health» on identifying patterns in the formation of mortality rates of the population dated January 20, 2021 No. 1, chaired by Deputy Prime Minister of the Russian Federation T.A. Golikova, experts of two directions - endocrinology and pathological anatomy, prepared a Draft of agreed recommendations on the Rules for coding the causes of death of patients with diabetes, causing the greatest problems in terms of the use of ICD-10 when choosing the initial cause of death, including in the case of death from CVD and COVID-19

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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