Background: Glucagon-like peptide 1 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. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.
The article is a summary of personal experience and literature data from PubMed, Scopus, Web of Science, ClinicalTrials.gov databases. As a result of the analysis, the main problems faced by practical endocrinologists when administering insulin therapy to patients with type 2 diabetes mellitus (T2DM) have been determined. Insulin therapy remains an important component of glucose-lowering therapy in T2DM. A significant increase in the number of oral hypoglycemic agents has allowed delaying the start of insulin therapy but the treatment for T2DM without insulin is not real today. The current problems of insulin therapy are as follows: untimely start, insufficient titration of the dose of basal insulin, excessive use of basal and bolus insulins, the irrationality of the use of premixes and the basis bolus regimen of insulin therapy. There are methods to overcome each of these issues that have proven their effectiveness according to clinical trials and real clinical practice data. The combination of insulin and oral therapy plays an important role, the addition of oral hypoglycemic agents is effective at different stages of insulin therapy. One of the most promising options is the use of fixed combinations of basal insulin with glucagon-like peptide-1 receptor agonists. Fixed combinations can be used as initial therapy and are often the first step when changing other insulin therapy regimens. The use of fixed combinations can be an option for modification (simplification) of complex insulin therapy regimens, including the basal bolus regimen. Authors review current evidence and circumstances in which insulin can be used, consider individualized choices of alternatives and combination regimens, and offer some guidance on personalized targets and approaches to glycemic control in type 2 diabetes. In general, most of the modern problems of insulin therapy have options for successful overcome.
Basal insulin is the first and main component of insulin therapy in patients with type 2 diabetes mellitus (T2DM). Based on the shortcomings of human NPH insulin and the advantages provided by long-acting basal insulin analogues, they are recommended for priority use in patients with T2DM. The leading factor in the success of insulin therapy is titration of its dose with the achievement of the target range of glycemia. Data from clinical trials and real clinical practice indicate that simpler dose titration algorithms ensure better achievement of glycemic goals with a lower risk of hypoglycemia. In addition, simple dose titration algorithms are better accepted by patients and increase satisfaction with treatment. The leading societies of diabetologists ADA/EASD and AACE/ACE recommend the use of simple dose titration algorithms. Recent clinical trials on the effectiveness of the insulin glargine dose titration based on the INSIGHT algorithm, which, unlike the traditional options for changing the dose 1–2 times a week, involves a daily correction of the insulin glargine dose by 1 Unit, have proven its effectiveness and safety. Most patients prefer this type of insulin dose titration. The same titration algorithm can be used for a fixed combination of glargine with lixisenatide, which was also confirmed by the results of clinical trials. In general, simplified options for correcting the basal insulin dose have demonstrated their effectiveness and allow increasing the percentage of patients who manage to achieve the glycemic goal without increasing the risk of hypoglycemia. When prescribing basal insulin, physician must determine the target range of glycemia, demonstrate the titration algorithm that is acceptable for each insulin and which a patient will use to achieve the glycemic goal.
Diabetes is a term used to denote a wide range of diseases. Diabetes mellitus unites conditions quite different in pathogenesis, but the leading feature for them is hyperglycemia and the complications caused by it. Among non-endocrinologists, the term “diabetes”, which literally means the flow of water as if through a siphon, is mostly perceived precisely in the context of carbohydrate metabolism disorders and the need for hypoglycemic therapy. Diabetes insipidus the symptom of which is also polyuria, but which has a completely different pathogenesis and requires different treatment is quite often misunderstood precisely because of the use of the term “diabetes”. Incorrect perception of this pathological condition leads to the prescription of incorrect, unnecessary treatment or, on the contrary, to the cancellation of replacement therapy, which can lead to the development of serious adverse events, including irreversible ones. That is why it is urgent to change the name of diabetes insipidus with the exclusion of the term “diabetes” to eliminate misunderstandings and ensure the safety of patients. In October-November 2022, the working group for renaming diabetes insipidus synchronously published a statement in several leading medical sources on the feasibility of changing the name of diabetes insipidus. The working group of representatives of national and international endocrinology and pediatric endocrinology societies now proposes changing the name “diabetes insipidus” to “arginine vasopressin deficiency” for central etiology and “arginine vasopressin resistance” for nephrogenic etiology. The statement contains information about both the historical context and the rationale for the proposed name change. The main reason for the change is the issue of patient safety, as there is quite often confusion with diabetes mellitus, which leads to an inappropriate examination, unjustified treatment and can cause undesirable consequences, including serious ones. Changing the name of diabetes insipidus is also relevant for Ukraine, since the names of two different diseases in the Ukrainian language are even more similar than in the English version. That is why we consider it necessary to widely inform the medical community of Ukraine about the name change initiative and join its discussion and support.
The article presents the literature review of the possibilities of modern antidiabetic therapy in the prevention of chronic kidney disease in patients with type 2 diabetes mellitus. The mechanisms of development and features of kidney disease in type 2 diabetes mellitus are described. The results of most recent clinical trials for studying the possibility of nephroprotection with new groups of hypoglycemic agents are reviewed: dipeptidyl peptidase-4 inhi-bitors, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors. The advantages of usage and the nephroprotective effects of agonists of glucagon-like peptide-1 receptors and sodium-glucose loop cotransporter-2 inhibitors are determined. Particular attention is paid to the nephroprotective effect of sodium-glucose loop co-transporter inhibitors as the only class of drugs that have demonstrated a reduction in the rate of decrease in glomerular filtration rate in patients with diabetes. The expediency of further study of the efficacy of the combined use of sodium-glucose cotransporter-2 inhibitors and agonists of glucagon-like peptide-1 receptors in diabetic chronic kidney disease is indicated. For a long time, approaches to the treatment of diabetic kidney disease did not differ for patients with type 1 and type 2 diabetes. The studies of recent years have shown that new hypoglycemic drugs can not only lower blood glucose levels but also have a beneficial effect on renal function. The mechanisms of nephroprotective effects have not been fully studied, but it is clear that they are beyond the scope of improved glycemic control. The possibility of the nephroprotective effect of these drugs on a glomerular filtration rate in the range of 30–15 ml/min/1.73 m2 and below remains unexplored. The effect of the combined use of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors is also unclear: will this combination predominate over monotherapy, and, if so, to what extent?
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