Diabetes and obesity. The role of agonists glucagon-like peptide-1 of in the treatment of type 2 diabetes

Significant number of patients with type 2 diabetes mellitus are obese. It is known that even glucose intolerance, as well as diabetes, can lead to vascular complications. At the same time, weight loss can reduce the risk of type 2 diabetes in obese and pre-diabetic patients. According to available data, a significant decrease in the incretin effect is observed in patients with type 2 diabetes and obese individuals. Thus, a decrease in the incretin effect leads to a violation of the insulin response to the intake of carbohydrates, and, consequently, an increase in the level of glucose in the blood. It was also found that the decrease in the incretin effect in patients with type 2 diabetes can be associated with a lower secretion of glucagon-like peptide-1. The interest is represented by groups of antidiabetic drugs capable of regulating glycemia by affecting the secretion of insulin and glucagon, depending on its level. Such drugs include glucagon-like peptide-1 receptor agonists. The article shows the advantage of prolonged action in patients with type 2 diabetes and obesity of the glucagon-like peptide 1 receptor agonists (albiglutide, dulaglutide, exenatide with slow release) dosing 1 time a week

Initial investigation of efficacy and safety of a new dipeptidyl peptidase-4 inhibitor, gosogliptin, for type 2 diabetes in Russia

Current treatment strategies for type 2 diabetes mellitus (T2DM) are based on using safe and effective hypoglycaemic agents for preventing diabetic vascular complications and reducing the risks associated with weight gain and hypoglycaemia. These goals may be achieved using new agents with a fundamentally new mechanism of action: inhibitors of dipeptidyl peptidase-4 (DPP-4i). However, the wide distribution of this enzyme in the body is associated with extraglycaemic DPP-4i effects, both positive and negative. Thus, it is important to develop and implement new DPP-4i agents for clinical practice. Aim. To investigate the efficacy and safety of a novel DPP-4i, gosogliptin, for use as monotherapy and in combination with metformin vs. vildagliptin as monotherapy and in combination with metformin for patients with drug-naive type 2 diabetes in a multicentre, open, randomized clinical trial. Materials and methods. We enrolled 299 drug-naive type 2 diabetes patients; 149 patients were randomized to receive gosogliptin and 150 patients received tovildagliptin. These groups had similar baseline characteristics. After randomization, 12 weeks of monotherapy was administered to both groups. Further, it was decided to continue the monotherapy or in combination with metformin, depending on each patient. The results after the first 12 weeks are presented in this paper. Results. After 12 weeks of monotherapy, HbA1c levels decreased significantly from 8.61% to 7.41% (

Current data on the effectiveness of gliclazide and molecular mechanisms of action of the drug

With the growing prevalence of type 2 diabetes mellitus (T2DM) the possibility of treating it with available drugs is one of the main issues. Although glycemic control and reduction of micro- and macrovascular outcomes remain important aspects of treatment, the main limiting factors are the availability and cost of oral hypoglycemic agents. Although newer agents, such as sodium -glucose cotransporter 2 inhibitors, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor agonists, potentially being valuable for patients with insulin resistance and cardiovascular complications, they are relatively expensive and have limited availability. Second-generation sulfonylureas effectively reduce glycated hemoglobin and contribute to the prevention of micro- and macrovascular complications of T2DM The review substantiates the role of Gliclazide MR as a more affordable drug for the treatment of T2DM, the safety of which has been confirmed by many studies; cardio-and nephroprotective effects are shown, as well as mechanisms for influencing в-cells of the pancreas and extrapancreatic effects through activation of phospholipase C and the G-protein-сoupled-receptors (GPCR) are analyzed. The latest data on the assessment of adverse events of Gliclazide MR are presented in comparison with both other sulfonylureas and glucose-lowering drugs of other classes

Heart failure and diabetes mellitus: insight into comorbidity

Diabetes mellitus (DM) and heart failure (HF) are frequent comorbidities with a bidirectional relationship. Patients with HF have increased risk of developing DM, and those with DM are at greater risk of developing HF. HF does not fit clearly into the microangiopathy and macroangiopathy groups. It is known that coronary artery disease and arterial hypertension are the major causes of HF; however, it has been shown that DM can trigger functional and structural abnormalities in the myocardium via diabetic cardiomyopathy, a condition with either restrictive or dilated phenotype. While HF treatment is equally effective and safe in patients with and without DM, this statement is not applicable for antidiabetic treatment. Several antidiabetic drugs, such as rosiglitazone, pioglitazone and saxagliptin increase the risk of hospitalisation for HF, therefore these antidiabetic drugs are contraindicated in patients with DM and HF or patients at risk of developing HF. Despite a large number of clinical evidence, uncertainty about the safety of antidiabetic drugs in patients with HF always exists. In this review, the issues of DM treatment in patients with HF are addressed in detail

What are new opportunities for clinical practice the VERIFY study opens and which values for native diabetes patients? Joint conclusion on the advisory board results. November 6, 2019

According to key diabetic studies, the early use of metformin glucose lowering therapy is associated with a reduced risk of developing micro- and, in the long term, 10-year follow-up, macrovascular complications and cardiovascular mortality. Short-term studies results on combined glucose lowering therapy with metformin suggests that combination therapy can have several advantages on the one side from the effectiveness of glycemic control and on another side from positive effect on the development of complications of type 2 diabetes. The question of the start time of combined hypoglycemic therapy remains open. According to the results of recent large-scale studies, real world evidence data, careful glycemic control during the first year from the moment of diagnosis of type 2 diabetes is crucial for further management of the disease and slow the progression of complications. However, due to the fact that the clinical benefits of early combination therapy were not demonstrated in randomized clinical trials, this approach, despite the theoretical background, was not recommended for widespread use in international guidelines for the treatment diabetes patients. Russian algorithms on the treatment diabetes patients recommend combined glucose lowering therapy at the start of treatment at a HbA1c level of 1% higher than the target. A 5-year VERIFY study results were demonstrated long-term sustained glycemic control in combination with vildagliptin + metformin prescribed for native diabetes patients with relatively low HbA1c values, as well as the advantages of this approach in comparison with the standard strategy for phased intensification of monotherapy. The results of the VERIFY study provided a wealth of information to discuss early treatment intensification, the clinical benefits of this approach and a possible review of the treatment strategy for native diabetes patients

Diabetes mellitus type 2 in adults

Public organization “Russian Association of Endocrinologists”. Clinical guidelines.&nbsp

Diabetes mellitus type 1 in adults

Public organization “Russian Association of Endocrinologists”. Clinical guidlines

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Alogliptin – the new member of DPP-4 inhibitors class

This review presents data on the efficacy and safety of alogliptin, a new representative of the DPP-4 inhibitors, in adult patients with type2 diabetes mellitus (DM type 2) as monotherapy or in combination with metformin, pioglitazone, glibenclamide and insulin