Evaluation of the Vasoprotective Effects of Metformin versus Glibenclamide in Type 2 Diabetic Patients

Adiponectin (APN) is an adipokine with anti-inflammatory and anti-atherogenic properties decreased in type 2 diabetes mellitus (T2DM) that may influence endothelial function by regulating serum nitric oxide (NO) levels. The current study aimed to investigate the effect of two oral hypoglycemic drugs, Metformin and Glibenclamide (GLC), on circulating APN and NO levels and to find a correlation between APN and NO levels in type 2 diabetic patients. Fifty males and females previously diagnosed with T2DM were conducted in this trial and classified into groups: Group A involved 18 untreated patients with T2DM, group B involved 16 patients receiving Metformin monotherapy (1000 mg/day) for up to 1 year and group C involved 16 patients receiving GLC (5 mg/day) for up to 1 year. Circulating APN and NO were measured. Compared to GLC, Metformin therapy showed a significant increase in APN and NO levels in type 2 diabetic patients. Our findings established that Metformin has a protective effect on endothelial function, including increased APN and NO bioavailability, beyond its glucose-lowering effect.

Dispensation Patterns of Glucose-Lowering Drugs in Newly Diagnosed Type 2 Diabetes: Routine Data Analysis of Insurance Claims in Germany

Aims To describe dispensation patterns of glucose-lowering drugs in newly diagnosed type 2 diabetes in Germany. Materials and methods Based on claims data from four statutory health insurances (German Pharmacoepidemiological Research Database,>25 million insurants), all individuals with newly diagnosed type 2 diabetes were identified. Eligible patients had a first diagnosis for type 2 diabetes between January 2012 and December 2016. We analyzed the dispensation patterns of first-line glucose-lowering therapies initiated in the year after diabetes diagnosis and patterns of second-line therapies dispensed one year after first-line treatment. Results A total of 356,647 individuals with newly diagnosed type 2 diabetes were included (average age [SD]: 63.5 [13.4] years; 49.3% males). Of the 31.6% of individuals who were pharmacologically treated in the year after diagnosis, metformin monotherapy was most frequently dispensed (73.1%), followed by dual therapy of metformin and dipeptidyl peptidase-4 inhibitors (DPP-4is) (6.4%), and monotherapy with DPP-4is (2.9%). From 2012 through 2016, sulfonylurea dispensations were reduced by more than 50%. Dispensations for combination therapies with DPP-4is increased up to 10.6%. Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors contributed to 2% of all treatments. After a median of 5 months, 20.0% of individuals on pharmacological therapy initiated second-line glucose-lowering treatment. Conclusions Data from German statutory health insurances (2012 to 2016) showed that most individuals with newly diagnosed type 2 diabetes were dispensed metformin monotherapy in line with diabetes care guidelines. A substantial decrease in the use of sulfonylureas was observed after the introduction of DPP-4i and GLP-1 receptor agonists.

Type 2 diabetes mellitus in children and adolescents in the world and in Ukraine

Introduction. Recently, many studies have been devoted to the study of type 2 diabetes mellitus (DM2) worldwide. In most countries of the world, the increase in the prevalence of DM2 among children and adolescents is accompanied by an increase in childhood obesity. The presence of obesity or overweight in children can complicate the diagnosis of various types of DM. Detection and treatment of DM2 is extremely important for the society due to the wide range of severe diabetes complications.The aim of this work was to analyze the frequency of DM2 according to the Register of patients with DM, and to determine the state of glycemic control in children with DM2. Materials and methods. An analysis of glycemic control in children with DM2 who received various treatment regimens: with diet and lifestyle modifications, or with additional oral hypoglycemic agents (metformin monotherapy, or combination with insulin therapy). The glycemic control was assessed by measurement of glycated hemoglobin (HbA1c) level. Results. According to the data Register in Ukraine, the prevalence of DM among children has a tendency to rise — from 8.6 per 10 thousand children in 2005, to 13.14 — in 2019 year. The prevalence of DM2 in 2019 was 0.47 % of all cases of DM, and its prevalence contained 0.062 per 10 thousand children under 19 years of age with significant differences in the frequency of its diagnosis in different regions of Ukraine. We analyzed the state of glycemic control in children with DM2 aged from 9 up to 19 years old (Me 16.2 [15.5; 18.0]), with a disease duration 0.5—12 years (Me 4.5 [1.0] ; 7.5]). The age of diagnosis of DM2 was 2-17 years old (Me 11.7 [8.5; 15.0]), and 91.3 % of patients had obesity. Diet and lifestyle modifications were used in 34.8 % of patients, metformin monotherapy in 52.2 %, and metformin and insulin combination therapy in 13 % of patients. HbA1c values ​​ranged from 5.0 to 11.4 % (Me 7.2 % [5,8; 8,0]). The proportion of children who had ideal or optimal glycemic control (HbA1c 7.0—7.5 %) was 52.2 %, suboptimal (HbA1c 7.6—9.0 %) — 39.1 %, high-risk glycemic control (HbA1c> 9.1 %) — 8.7 % of children. The most unsatisfactory HbA1c levels ​​were registered in children who received metformin in combination with insulin (Me 10.6 % [10,15; 11,4]). Chronic complications of DM2 have not been reported.Conclusions. We found a low prevalence of DM2 among the pediatric population in Ukraine, more likely due to the low quality of its detection among children diagnosed with DM, as well as among children among high risk groups. Most children with DM 2 were obese. The majority of patients with DM2 (52.2 %) received metformin monotherapy, more than a third did not receive oral hypoglycemic agents. In most children with DM2 (52,2 %), the state of glycemic control corresponded to the optimal (< 7.5 %), but higher levels of HbA1c were found children who received metformin in combination with insulin.

Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome

The present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome. This study included patients who admitted in Jiangxi Provincial People’s Hospital from January 1, 2017 to December 31, 2019 and were diagnosed with metabolic syndrome. A total of 248 participants were randomly assigned to divide into three groups: dapagliflozin group; metformin group; dapagliflozin in combined with metformin group. Dapagliflozin group and metformin group were associated with similar improvements in components of metabolic syndrome. Relative to dapagliflozin or metformin monotherapy, dapagliflozin combined with metformin provided greater improvements in components of metabolic syndrome. So did HOMA-IR scores, fasting plasma insulin and inflammatory indicators (hsCRP, PMN/HDL-C and Monocytes/HDL-C). Dapagliflozin improved all components of metabolic syndrome in patients with metabolic syndrome. Furthermore, dapagliflozin combined with metformin showed more meaningful improvements in any of components of metabolic syndrome than dapagliflozin or metformin monotherapy.

Type 2 diabetes reversal with digital twin technology-enabled precision nutrition and staging of reversal: a retrospective cohort study

Background Type 2 diabetes reversal has been viewed in the literature primarily as a dichotomous event (reversed or not reversed), even though this viewpoint may not be optimal for clinicians or patients. This cohort study’s objectives were to define stages of type 2 diabetes reversal and measure changes in reversal stages before and after 90 days of digital twin-enabled precision nutrition therapy. Methods This study defines seven stages of diabetes reversal. The study is a retrospective pre/post comparison of changes in reversal stage, hemoglobin A1c (HbA1c), weight, body mass index (BMI), and other metrics measured before and after precision nutrition therapy. Reversal stages were defined as Stage 0: HbA1c < 5.7% without medication for > 1 year, Stage 1: HbA1c < 5.7% without medication for < 1 year, Stage 2: HbA1c < 6.5% without medication, Stage 3: estimated HbA1c (eA1c) between 5.7 and 6.4% without medication, Stage 4: estimated HbA1c (eA1c) between 5.7 and 6.4% with metformin monotherapy, Stage 5: dual oral therapy, Stage 6: > = 3 medications. Results Reversal stage information was available for 463 patients at baseline and 90 days. At baseline, the proportions of patients in each reversal stage were Stages 1 and 2: 0%, Stage 3: 1%, Stage 4: 8%, Stage 5: 6%, and Stage 6: 85%. After 90 days, the proportions in each reversal stage were Stage 1: 2%, Stage 2: 9%, Stage 3: 32%, Stage 4: 39%, Stage 5: 7%, and Stage 6: 11%, indicating significant progress. Reversal stage progression rates varied by patient subgroup. Conclusions Type 2 diabetes patients reached differing reversal stages during 90 days of precision nutrition therapy. Use of reversal stages may benefit patients during therapy. Trial registration This was a retrospective study that was approved by the Medisys Clinisearch Ethical Review Board (without registration number) in 2019.

Low risk of hypoglycemia and high efficacy of gliclazide MB: results of recent studies

Sulfonylureas are widely prescribed all over the world, mainly because of their high effectiveness. At the same time, the heterogeneity of the group is obvious, primarily in relation to the effect of drugs on the risk of developing hypoglycemic events. The review presents the results of new studies, including «Comparative effectiveness of gliclazide modified release versus sitagliptin as second-line treatment after metformin monotherapy in patients with uncontrolled type 2 diabetes» and results of a model-based meta-analysis of 24 antihyperglycemic drugs for type 2 diabetes, confirming the higher efficacy of modified release gliclazide (gliclazide MB) compared to DPP-4, as well as a low risk of hypoglycemic conditions. The results of recent studies, as well as the results of the ADVANCE and ADVANCE-ON studies, suggest that gliclazide MB is safe to use as a second-line drug, especially in patients with chronic kidney disease.

Oral Antidiabetics and Sleep Among Type 2 Diabetes Patients: Data From the UK Biobank

Previous small-scale studies have found that oral antidiabetic therapy is associated with sleep difficulties among patients with type 2 diabetes (T2D). Here, we used data from 11 806 T2D patients from the UK Biobank baseline investigation to examine the association of oral antidiabetic therapy with self-reported difficulty falling and staying asleep and daily sleep duration. As shown by logistic regression adjusted for, e.g., age, T2D duration, and HbA1c, patients on non-metformin therapy (N=815; 86% were treated with sulphonylureas) had a 1.24-fold higher odds ratio of reporting regular difficulty falling and staying asleep at night compared to those without antidiabetic medication use (N=5 366, P&lt;0.05) or those on metformin monotherapy (N=5 625, P&lt;0.05). Non-metformin patients reported about 8 to 10 minutes longer daily sleep duration than the other groups (P&lt;0.05). We did not find significant differences in sleep outcomes between untreated and metformin patients. Our findings suggest that non-metformin therapy may result in sleep initiation and maintenance difficulties, accompanied by a small but significant sleep extension. The results of the present study must be replicated in future studies using objective measures of sleep duration and validated questionnaires for insomnia. Considering that most T2D patients utilize multiple therapies to manage their glycemic control in the long term, it may also be worth investigating possible interactions of antidiabetic drugs on sleep.

Metformin monotherapy is an effective alternative for management of gestational diabetes mellitus in patients refusing insulin monotherapy

A clinical decision report using: Ghomian N, Vahed SHM, Firouz S, Yaghoubi MA, Mohebbi M, Sahebkar A. The efficacy of metformin compared with insulin in regulating blood glucose levels during gestational diabetes mellitus: A randomized clinical trial. J Cell Physiol. 2019;234(4):4695-4701. https://doi.org/10.1002/jcp.27238 for a patient with gestational diabetes mellitus (GDM) who does not wish to undergo insulin monotherapy.