Pharmacotherapy Of Type Research Articles

Rational Pharmacotherapy in Type 2 Diabetes: Danish Data From 2002 to 2020 on Mortality, Diabetes- Related Outcomes, Adverse Events, and Medication Expenses.

Developments in pharmacotherapy and management of type 2 diabetes may have shifted the balance of treatment benefits versus harms and costs over the past decades. This study aimed to describe the trends in this balance. We followed the Danish population with type 2 diabetes between 2002 and 2020, analyzing their medication use in relation to treatment benefits (such as mortality and diabetes-related outcomes), adverse events, and medication costs. Using multivariate analyses, we adjusted for potential confounders, including age, sex, and socioeconomic status. The study included 461,805 individuals. From 2002 to 2020, the median age increased from 66 to 68 years, and the mean number of comorbidities increased from 5.2 to 8.8. The overall incidence of cardiovascular, renal, and other important adverse clinical outcomes decreased. Similarly, the rate of some adverse events, such as gastric bleeding, hypoglycemia, and falls declined, whereas the incidence of electrolyte imbalances and ketoacidosis increased. The average per-patient cost was reduced by 8%, but total medication expenses increased by 148% due to an expanding population size, lowered costs of most cardiovascular medications, and increasing costs for glucose-lowering drugs. Advancements in type 2 diabetes management have led to reduced risk of both diabetes-related outcomes and treatment harms, while maintaining relatively stable per-patient medication expenses. Although these trends are multifactorial, they suggest more rational pharmacotherapy. Still, increased risk of certain adverse events, along with increasing costs for glucose-lowering medications, underscores the need for ongoing vigilance and risk-benefit analysis.

Effect of Drugs Used in Pharmacotherapy of Type 2 Diabetes on Bone Density and Risk of Bone Fractures.

This review summarizes the complex relationship between medications used to treat type 2 diabetes and bone health. T2DM patients face an increased fracture risk despite higher bone mineral density; thus, we analyzed the impact of key drug classes, including Metformin, Sulphonylureas, SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists, and Thiazolidinediones. Metformin, despite promising preclinical results, lacks a clear consensus on its role in reducing fracture risk. Sulphonylureas present conflicting data, with potential neutral effects on bone. SGLT-2 inhibitors seem to have a transient impact on serum calcium and phosphorus, but evidence on their fracture association is inconclusive. DPP-4 inhibitors emerge as promising contributors to bone health, and GLP-1 agonists exhibit positive effects on bone metabolism, reducing fracture risk. Thiazolidinediones, however, demonstrate adverse impacts on bone, inducing loss through mesenchymal stem cell effects. Insulin presents a complex relationship with bone health. While it has an anabolic effect on bone mineral density, its role in fracture risk remains inconsistent. In conclusion, a comprehensive understanding of diabetes medications' impact on bone health is crucial. Further research is needed to formulate clear guidelines for managing bone health in diabetic patients, considering individual profiles, glycemic control, and potential medication-related effects on bone.

Early metformin initiation was not associated with incident dementia: a population‐based cohort study

AbstractBackgroundMetformin is the first‐line pharmacotherapy for type 2 diabetes. Although metformin was previously suggested to prevent dementia, most existing epidemiologic studies did not adequately address immortal time bias or confounding due to disease severity. We aim to determine the association of metformin with dementia risk using various bias mitigation strategies.MethodThis population‐based retrospective cohort study utilized data housed at ICES (https://www.ices.on.ca/). Using a validated algorithm for diabetes (Specificity = 99.1%, PPV = 91.4%), residents of Ontario, Canada ≥66 years newly diagnosed with diabetes from January 1, 2008 to December 31, 2017 entered the cohort. We excluded potential type 1 diabetes or advanced diabetes cases by excluding people with insulin as the first received glucose‐lowering medication. To select people at an early disease stage who could either initiate metformin or start lifestyle interventions alone, we excluded people with hemoglobin A1c <6.5% or ≥8.0% or estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2. Using a landmark analysis to address immortal time bias, the exposure was classified into “metformin monotherapy initiation within 180 days after new diabetes diagnosis” or “no glucose‐lowering medications within 180 days”. To mitigate reverse causality, a 1‐year lag period was applied to the end of the 180‐day landmark period, and therefore follow‐up started 1.5 year after cohort entry. Incident dementia was ascertained using a validated algorithm for Alzheimer’s disease and related dementias (Sensitivity = 79.3%, Specificity = 99.1%). Adjusted hazard ratios (aHR) and confidence intervals (CI) were obtained from propensity‐score weighted Cox proportional hazard models.ResultCompared to no or delayed metformin initiation (N = 22,369; 1,768 events; 117,414 person‐years), metformin initiation within 180 days (N = 12,331; 978 events; 65,761 person‐years) showed no association (aHR [95% CI] = 1.047 [0.956‐1.147]) with dementia risk over mean follow‐up of 5.28 years. The sensitivity analysis with a 1‐year landmark period also showed no association (aHR [95% CI] = 1.040 [0.942‐1.148]) when comparing metformin initiation within 1 year (N = 13,902; 1,047 events; 68,404 person‐years) to no or delayed initiation (N = 19,078; 1,433 events; 91,917 person‐years).ConclusionEarly metformin initiation was not associated with a lower dementia risk. The present study does not support metformin as a drug to prevent dementia.

Editor's Summaries of the Articles Published in This Issue of Precision Medicine Communications

In this issue, Rafiq et al, investigated noncancerous FDA-approved drugs for repurposing through molecular docking studies in Breast Cancer patients after their target cystic fibrosis transmembrane conductance regulator protein (CFTR) detection in breast cancer patients. Konain and colleagues evaluate the anticancer potential of commonly used angiotensin receptor blocker (ARB) telmisartan and validate it through molecular techniques, Bangash and friends investigate whether the efficacy and adverse effects of fluvoxamine are associated with polymorphism in the CYP2D6 gene in patients with depression; Mubarak and colleagues reviewed studies aimed at investigating resistance to Carbamazepine in epilepsy patients influenced by the polymorphism of genes encoding metabolic enzymes and drug transporters, while Riaz and Chen provide general information about Type 2diabetes mellitus, treatment challenges, and pharmacogenetic aspects of metformin pharmacotherapy in type 2 diabetes mellitus.

An Update on the Molecular and Cellular Basis of Pharmacotherapy in Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is a chronic illness with an increasing global prevalence. More than 537 million cases of diabetes were reported worldwide in 2021, and the number is steadily increasing. The worldwide number of people suffering from DM is projected to reach 783 million in 2045. In 2021 alone, more than USD 966 billion was spent on the management of DM. Reduced physical activity due to urbanization is believed to be the major cause of the increase in the incidence of the disease, as it is associated with higher rates of obesity. Diabetes poses a risk for chronic complications such as nephropathy, angiopathy, neuropathy and retinopathy. Hence, the successful management of blood glucose is the cornerstone of DM therapy. The effective management of the hyperglycemia associated with type 2 diabetes includes physical exercise, diet and therapeutic interventions (insulin, biguanides, second generation sulfonylureas, glucagon-like peptide 1 agonists, dipeptidyl-peptidase 4 inhibitors, thiazolidinediones, amylin mimetics, meglitinides, α-glucosidase inhibitors, sodium-glucose cotransporter-2 inhibitors and bile acid sequestrants). The optimal and timely treatment of DM improves the quality of life and reduces the severe burden of the disease for patients. Genetic testing, examining the roles of different genes involved in the pathogenesis of DM, may also help to achieve optimal DM management in the future by reducing the incidence of DM and by enhancing the use of individualized treatment regimens.

Effect of the Ketogenic Diet on the Prophylaxis and Treatment of Diabetes Mellitus: A Review of the Meta-Analyses and Clinical Trials.

The exponentially growing frequency of diagnosing diabetes mellitus means that a verification of the previous dietetic approach to treating the disease seems justified. The simultaneous growth of interest in the ketogenic diet and the development of knowledge in this field have contributed to the increasingly frequent application of the ketogenic diet in diabetes treatment. This paper also deals with that issue; its aim includes an extensive analysis of the influence of the ketogenic diet on the prophylaxis and treatment of diabetes. The paper has been prepared based on a wide, meticulous analysis of the available literature on the subject. Among other findings, a favorable effect of that nutrition model has been demonstrated on the values of glycated hemoglobin, glucose, insulin, or other metabolic parameters in diabetes patients. The effect of the ketogenic diet on the pharmacotherapy of type 1 and type 2 diabetes has been presented and compared with the standard nutritional management plan recommended for that disease. Further research is needed in this field, especially studies with a long follow-up period. The discussed articles report interesting therapeutic advantages to the ketogenic diet in comparison with standard diets.

Clinical pharmacology of antidiabetic drugs: What can be expected of their use?

The pharmacotherapy of type 2 diabetes mellitus (T2DM) has markedly evolved in the last two decades. Classical antidiabetic agents (sulphonylureas, metformin, insulin) are now in competition with new glucose-lowering medications. Alpha-glucosidase inhibitors and thiazolidinediones (glitazones) were not able to replace older agents, because of insufficient efficacy and/or poor tolerability/safety. In contrast, incretin-based therapies, both dipeptidyl peptidase-4 inhibitors (DPP-4is or gliptins, oral agents) and glucagon-like peptide-1 receptor agonists (GLP-1RAs, subcutaneous injections) are a major breakthrough in the management of T2DM. Because they are not associated with hypoglycaemia and weight gain, DPP-4is tend to replace sulphonylureas as add-on to metformin while GLP-1RAs tend to replace basal insulin therapy after failure of oral therapies. Furthermore, placebo-controlled cardiovascular outcome trials demonstrated neutrality for DPP-4is, but cardiovascular protection for GLP-1RAs in patients with T2DM at high cardiovascular risk. More recently sodium-glucose cotransporter 2 inhibitors (SGLT2is or gliflozins, oral agents) also showed cardiovascular protection, especially a reduction in hospitalization for heart failure, as well as a renal protection in patients with and without T2DM, at high cardiovascular risk, with established heart failure and/or with chronic kidney disease. Thus, GLP-1RAs and SGLT2is are now considered as preferred drugs in T2DM patients with or at high risk of atherosclerotic cardiovascular disease whereas SGLT2is are more specifically recommended in patients with or at risk of heart failure and renal (albuminuric) disease. The management of T2DM is moving from a glucocentric approach to a broader strategy focusing on all risk factors, including overweight/obesity, and to an organ-disease targeted personalized approach.

Sodium-Glucose Cotransporter-2 Inhibitors-from the Treatment of Diabetes to Therapy of Chronic Heart Failure.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are currently the second-line pharmacotherapy in type 2 diabetes, particularly through their effectiveness in reducing glycemia, but also due to their cardioprotective and nephroprotective effects. In light of surprisingly satisfactory results from large, randomized trials on gliflozins, SGLT2 received the highest recommendation (Class IA) with the highest level of evidence (A) in the treatment algorithm for HF with reduced LVEF in recent ESC HF guidelines. This great breakthrough in the treatment of HF is due to different mechanisms of action of gliflozins that are reported to be able to change the natural course of HF by reducing the risk of both hospitalization and death. They are recommended regardless of the patient’s diabetes status. This review summarizes the up-to-date literature on their beneficial and pleiotropic impact on the cardiovascular system.

A Comparative Study to Evaluate the Pharmacotherapy of Type II Diabetes in Patients Visiting Tertiary Care Teaching Hospital and Private Clinic

Introduction: Diabetes mellitus (DM) refers to a bunch of disorders of metabolism that share the phenotypic sign of hyperglycemia. Different variants of DM are caused due to the interaction of various genetic factors with environmental factors. Materials and Methods: This is prospective, comparative, and observational study. The study was conducted at SMBT Medical Institute and Research Centre Dhamangaon Nashik and private Diabetic clinic. Each center was 50 purposive sampling. Inclusion Criteria: All those patients who are diagnosed with Type II Diabetes and age of 18 years and above belonging to either gender were included in the study. Exclusion Criteria: Patients who are not willing to sign the informed consent were excluded from the study. Those individuals who are having Type I diabetes and suffering from co-morbid conditions such as hypertension, hyperthyroidism, and immune deficiency syndrome were excluded. Results: In our study, results revealed that mono and combination therapies for the treatment of type II DM. The present study revealed that most of the physicians initially prescribed mono therapy (25%) includes Metformin/Glibenclamide/Glimepiride/Gliclazide to control hyperglycemia followed by dual therapy (35%) FDC of Metformin + Pioglitazone/Metformin + Glipizide/Metformin + Glimepiride/Metformin + Saxagliptin/Metformin + Voglibose and triple therapy (40%) includes Metformin + Glimepiride + Pioglitazone in group A. In Group B, mono therapy (35%) and triple therapy (35%) were used more commonly over dual therapy (30%) to control hyperglycemic. Conclusion: Hence, while comparing between tertiary care versus private care hospital, Group A: Biguanide: Metformin and Sulfonylureas: Glibenclamide, Glipizide, Gliclazide, and Glimepiride was most commonly prescribed drug. In Group B: Dapagliflozin (Sodium-glucose co-transport-2 inhibitors) and Teneligliptin: Dipeptidyl peptidase-4 inhibitors were most commonly used in private hospital.

Prospects for application of phytopreparations in the complex treatment of type 2 diabetes mellitus

Diabetes mellitus (DM) occupies an important place in the structure of mortality, as well as among the causes of disability and deterioration in the quality of life of the population. In this regard, the study of phytopreparations is promising for practical medicine in order to identify new medicinal plants that actively affect metabolic processes to prevent complications of DM, and create new phytopreparations. That drugs could enhance the effect of sulfonamides and potentiate the effect of insulin, thereby reducing the dose of the latter, and it is important for long-term chronic diseases, such as DM.
 The aim. To study the prospects for the use of phytopreparations in the complex treatment of type 2 diabetes mellitus.
 Materials and methods. The analytical, logical, generalization methods were used in the work. The analytical method of the study involved deepening the search for phytopreparations and the prospects for their use in the complex treatment of type 2 diabetes mellitus and generalization of the data obtained. The logical method of exploratory research of promising phytopreparations was applied in a certain logical sequence, as a result of which the specificity, stage-by-stage and generalization of the relevance of the use of phytopreparations in the complex treatment of type 2 diabetes mellitus was provided for scientific research. The generalizing research method was to determine and prove the characteristics of phytopreparations (analysis and synthesis) and their advantages over synthetic drugs.
 Results and discussion. The main directions of herbal medicine for DM are associated with reproduction of the effects of insulin, normalization of glucose uptake, stimulation of regeneration of β-cells of the Langerhans islets, elimination of excess glucose from the body – phytopreparations with diuretic properties; elimination of hypoxia – phytopreparations-antihypoxants. In DM, herbal medicine will reduce the frequency of side effects in classical antidiabetic therapy. For any type of diabetes, herbal medicine is prescribed to patients as an improvement in the microcirculation of tissues, normalization of the functions of the cardiovascular and nervous systems, kidneys and eyes.
 Conclusions. Despite a wide range of drugs used to correct the hemodynamic and metabolic manifestations of the insulin resistance syndrome, they do not fully meet the needs of practical medicine due to the presence of pronounced side effects. In addition, the pharmaceutical market of herbal medicines is very limited and represented mainly by species of medicinal plants, which have certain inconveniences in their use. All this indicates the relevance of the search, creation and introduction of effective and, at the same time, low-toxic drugs based on the medicinal plant raw material into medical practice for the pharmacotherapy of type 2 diabetes and its complications

Metformin Targets Foxo1 to Control Glucose Homeostasis.

Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus (T2D). Metformin exerts its glucose-lowering effect primarily through decreasing hepatic glucose production (HGP). However, the precise molecular mechanisms of metformin remain unclear due to supra-pharmacological concentration of metformin used in the study. Here, we investigated the role of Foxo1 in metformin action in control of glucose homeostasis and its mechanism via the transcription factor Foxo1 in mice, as well as the clinical relevance with co-treatment of aspirin. We showed that metformin inhibits HGP and blood glucose in a Foxo1-dependent manner. Furthermore, we identified that metformin suppresses glucagon-induced HGP through inhibiting the PKA→Foxo1 signaling pathway. In both cells and mice, Foxo1-S273D or A mutation abolished the suppressive effect of metformin on glucagon or fasting-induced HGP. We further showed that metformin attenuates PKA activity, decreases Foxo1-S273 phosphorylation, and improves glucose homeostasis in diet-induced obese mice. We also provided evidence that salicylate suppresses HGP and blood glucose through the PKA→Foxo1 signaling pathway, but it has no further additive improvement with metformin in control of glucose homeostasis. Our study demonstrates that metformin inhibits HGP through PKA-regulated transcription factor Foxo1 and its S273 phosphorylation.

Weight Outcomes With Empagliflozin as Compared With Liraglutide in Veterans With Type 2 Diabetes Mellitus.

Glucagon-like peptide-1 agonists and sodium glucose cotransporter 2 inhibitors are associated with weight loss and improved cardiovascular outcomes, and are increasingly used in pharmacotherapy for type 2 diabetes mellitus (T2DM). To compare weight loss outcomes of empagliflozin and liraglutide in patients with T2DM and overweight/obesity not yet prescribed insulin but requiring additional pharmacotherapy to improve glycemic control. This is an observational, multisite, cohort study of veterans with T2DM prescribed liraglutide or empagliflozin. Participants were prescribed either empagliflozin or liraglutide prior to November 1, 2017, had a hemoglobin A1C (A1C) ≥7.0%, had a body mass index ≥27 kg/m2, and were not treated with insulin at baseline. The primary outcome was change in weight after 1 year using multiple regression. Secondary outcomes were the proportion achieving ≥5% weight loss and change in A1C. Weight loss was not significantly different between groups: -2.17 kg (95% CI: -2.91 to -1.42) in the liraglutide group (n = 298) and -2.81 kg (95% CI: -3.43 to -2.20) in the empagliflozin group (n = 247; P > 0.05). After adjusting for covariates, this effect remained nonsignificant. There was no difference in change in A1C between liraglutide (-0.83%; 95% CI: -1.05% to -0.62%) and empagliflozin (-0.71%; 95% CI: -0.89% to -0.53%; P > 0.05). There was no significant difference in weight outcomes after 1 year in veterans treated with liraglutide versus empagliflozin. Because both medications did show modest weight loss, both remain good options for patients needing an additional medication to improve glycemic control that is at least weight neutral.

Preventive pharmacotherapy of type 2 diabetes mellitus in patients with early carbohydrate metabolism disorders: long-term efficacy and clinical outcomes

Актуальность профилактики сахарного диабета (СД) 2-го типа у пациентов с предиабетом увеличивается из-за неуклонного распространения заболевания. Целью работы было оценить эффективность медикаментозной профилактики в замедлении темпов конверсии впервые выявленных нарушенной толерантности к глюкозе и нарушенной гликемии натощак (НТГ/НГН) в СД 2-го типа. Участникам исследования (1136 человек), считавшимся здоровыми после диспансеризации, повторно провели скрининг СД 2-го типа с соблюдением правил преаналитической подготовки образцов крови. Пациентам с впервые выявленными НТГ/НГН была назначена терапия метформином и/или акарбозой, частоту конверсии НТГ/НГН в СД 2-го типа оценивали через 3 и 10 лет наблюдения. У 18,5% (n = 210) обследованных выявили различные категории нарушения углеводного обмена: СД 2-го типа — у 5,0%, НТГ — у 5,5%, НГН — у 8,0%. Пациентам с впервые выявленным СД 2-го типа была назначена сахароснижающая терапия, они были исключены из последующего наблюдения. Пациентам с НТГ/НГН (n = 151) рекомендовали изменение образа жизни и назначили терапию метформином (77%) или метформином и акарбозой (23%). Частота конверсии СД 2-го типа в течение 3 лет активного наблюдения составила 6,8% на фоне монотерапии метформином и 11,4% — на фоне комбинированной терапии метформином и акарбозой. По окончании периода активного наблюдения большинство пациентов (n = 85) самостоятельно прекратили терапию. Частота конверсии НТГ/НГН в СД 2-го типа через 10 лет после окончания активного наблюдения в группе без медикаментозной профилактики составила 38,8% и 0% — в группе ринимающих метформин (p < 0,01). Показано, что длительное применение метформина предупредило развитие СД 2-го типа в отдаленном периоде у 83,3% (p < 0,05).

METFORMIN EXERTS CARDIOPROTECTION IN ISOPROTERENOL-INDUCED CARDIOMYOPATHY IN RATS

Introduction. Due to neuropathy in diabetic patients, the dysfunction of the autonomic nervous system occurs, and cardiac activity undergone excess sympathetic stimulation which is named cardiac autonomic neuropathy. Patients with cardiac autonomic neuropathy are at higher risk of left ventricular hypertrophy and are predisposed to cardiovascular events. It was established that metformin, a first-line agent for the initial pharmacotherapy of type 2 diabetes mellitus, poses significant cardioprotective effects. Nevertheless, its activity in the myocardium, subjecting the increased sympathetic tone, remains poorly investigated.
 The aim of the study – to explore the effects of metformin on cardiac remodeling after prolonged isoproterenol administration at a low dose.
 Research Methods. To induce cardiomyopathy, Wistar rats were injected intraperitoneally with isoproterenol (Iso – 5 mg/kg) in the continuous presence of metformin (М – 100 mg/kg) or vehicle only for 7 consecutive days. Tissue samples were stained with Hematoxylin&Eosin using standard method. The serum level of brain natriuretic peptide was estimated using the Rat BNP ELISA Kit. Statistical comparison of multiple groups was performed by one-way ANOVA followed by Bonferroni Test using GraphPad Prism version 5.00.
 Results and Discussion. The results of investigation demonstrate that metformin treatment significantly aboli­shed cardiac hypertrophy in rats induced by isoproterenol administration at the daily dose 5 mg/kg for 7 days. Anti­hypertrophic effect of the drug was confirmed by its ability to diminish the serum level of brain natriuretic peptide. Structural fibrotic reorganization was prevented as well.
 Conclusions. Metformin exerts cardioprotection after prolonged isoproterenol administration at a low dose preventing hypertrophic and fibrotic remodeling and fetal genes reprogramming. Thus, it might be a potential tool in the prevention of cardiac remodeling in patients with sympathetic overactivity.

Preventive pharmacotherapy of type 2 diabetes mellitus in patients with early carbohydrate metabolism disorders: long-term efficacy and clinical outcomes

Prevention of type 2 diabetes mellitus (T2DM) in prediabetic patients is a pressing concern due to its increasing prevalence. The aim of this study was to evaluate the efficacy of preventive pharmacotherapy in delaying progression of incident impaired glucose tolerance (IGT) and impaired fasting glycemia (IFG) to T2DM. The participants of the study (1,136 subjects) found healthy by a regular annual checkup underwent repeat screening for T2DM. Blood samples were processed following the guidelines for good preanalytical sample preparation. Patents with incident IGT/IFG were prescribed medication therapy with metformin or/and acarbose. The rate of IGT/IFG conversion to T2DM was evaluated in years 3 and 10 of observation. Carbohydrate metabolism disorders were detected in 18.5% (n = 210) of the re-screened patients: 5.0% had T2DM, 5.5% had IGT, 8.0% had IFG. Patients with incident T2DM were prescribed blood sugar lowering therapy and they were excluded from further analysis. Patients with IGT/IFG (n = 151) were given recommendations on lifestyle modification and prescribed metformin (77%) or a combination of metformin and acarbose (23%). Three years after the start of observation, the rate of conversion to T2DM was 6.8% in patients undergoing monotherapy with metformin and 11.4% in patients undergoing combination therapy with metformin and acarbose. After the active follow-up phase was over, the majority of the patients (n = 85) decided to discontinue preventive therapy without consulting their physicians. Ten years after the active follow-up phase, the rate of NGT/IFG conversion to T2DM was 38.8% in patients who had discontinued their treatment and 0% in patients still taking metformin (p < 0.01). Long-term therapy with metformin prevented progression to T2DM in the long run in 83.3% (p < 0.05).

Możliwości personalizacji farmakoterapii cukrzycy typu 2 na podstawie profilu genetycznego pacjenta

Możliwości personalizacji farmakoterapii cukrzycy typu 2 na podstawie profilu genetycznego pacjenta

Agonism of receptors in the gut–pancreas axis in type 2 diabetes: are two better than one?

Pharmacotherapy for type 2 diabetes has become complex with the advent of a large number of treatment options. Major goals of therapy include achieving glycaemic targets (glycated haemoglobin [HbA1c] ≤7%) to minimise the development and progression of microvascular and, to a lesser extent, macrovascular complications, while avoiding hypoglycaemia. 1 Inzucchi SE Bergenstal RM Buse JB et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015; 38: 140-149 Crossref PubMed Scopus (2102) Google Scholar Obesity is a key risk factor of type 2 diabetes—hence, the terminology diabesity. 2 Zimmet P Alberti KG Shaw J Global and societal implications of the diabetes epidemic. Nature. 2001; 414: 782-787 Crossref PubMed Scopus (4542) Google Scholar Weight loss, even when modest, might improve not only glycaemic control and cardiovascular risk but also hepatic steatosis—the non-alcoholic fatty liver disease that is now the most common cause of chronic liver disease globally. 3 Diehl AM Day C Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med. 2017; 377: 2063-2072 Crossref PubMed Scopus (619) Google Scholar MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a studyMEDI0382 has the potential to deliver clinically meaningful reductions in blood glucose and bodyweight in obese or overweight individuals with type 2 diabetes. Full-Text PDF

Investigation of hypoglycemic properties of ginger extract on type 2 diabetes mellitus experimental model, caused by dexamethasone

Topicality. In pharmacotherapy of type 2 diabetes mellitus and metabolic syndrome, whose complex of disorders develops against the background of insulin resistance, medicinal plants are used as an important prophylactic and therapeutic additon, which causes the urgency of developing new domestic anti-diabetic herbal medicinal products.Aim. To study the anti-hyperglycemic properties of the extract of ginger on the experimental model of type 2 diabetes induced by dexamethasone.Materials and methods. Type 2 diabetes mellitus was reproduced by subcutaneous administration of dexamethasone at a dose of 0.125 mg/kg to rats for 13 days. Antihyperglycemic effect was assessed on day 14 for the concentration of glucose and insulin in the blood serum and the insulin resistance index.Results and discussion. The results of the study showed that ginger extract in doses of 50 and 80 mg/kg had a pronounced antihyperglycemic effect, which, according to obtained results, is implemented due to its ability to improve the sensitivity of peripheral tissues to the action of insulin, and thus to reduce the manifestations of insulin resistance.The use of the extract of ginger in a dose of 80 mg/kg revealed the most pronounced correction of the parameters of carbohydrate metabolism. The severity of the anti-hyperglycemic effect of the extract of ginger at a dose of 80 mg/kg is comparable to the effect of harvesting Arfazetine.Conclusions. The obtained results justify the expediency of further studying the extract of ginger at a dose of 80 mg/kg as a promising antidiabetic agent.

Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes.

Despite a position as the first-line pharmacotherapy in type 2 diabetes, the glucose-lowering mechanisms of metformin remain to be fully clarified. Gut-derived modes of action, including suppression of bile acid reabsorption and a resulting increase in glucagon-like peptide-1 (GLP-1) secretion, have been proposed. The aim of this study was to assess the GLP-1 secretory and glucometabolic effects of endogenously released bile, with and without concomitant single-dose administration of metformin in patients with type 2 diabetes. Randomized, placebo-controlled, and double-blinded crossover study. This study was conducted at Center for Diabetes Research, Gentofte Hospital, Denmark. Fifteen metformin-treated patients with type 2 diabetes; all participants completed the study. Four experimental study days in randomized order with administration of either 1500 mg metformin or placebo in combination with intravenous infusion of cholecystokinin (0.4 pmol × kg-1 × min-1) or saline. Plasma GLP-1 excursions as measured by baseline-subtracted area under the curve. Single-dose metformin further enhanced bile acid-mediated induction of GLP-1 secretion (P = 0.02), whereas metformin alone did not increase plasma GLP-1 concentrations compared with placebo (P = 0.17). Metformin, both with (P = 0.02) and without (P = 0.02) concomitant cholecystokinin-induced gallbladder emptying, elicited reduced plasma glucose excursions compared with placebo. No GLP-1-mediated induction of insulin secretion or suppression of glucagon was observed. Metformin elicited an enhancement of the GLP-1 response to cholecystokinin-induced gallbladder emptying in patients with type 2 diabetes, whereas no derived effects on insulin or glucagon secretion were evident in this acute setting.

Marked recovery from glucotoxicity of β-cell function after medical nutrition therapy without pharmacotherapy in type 2 diabetic outpatients with extreme hyperglycemia: a pilot retrospective study.

We investigated whether glucotoxicity of β-cell function could be eliminated after medical nutrition therapy (MNT) without forced correction of hyperglycemia by anti-diabetic medications including exogenous insulin administration. We analyzed newly diagnosed type 2 diabetic outpatients with hemoglobin A1c (HbA1c) of 10.1 ± 1.5%, who were treated by MNT at least for three months, without any aid of anti-diabetic medications. The β-cell function was calculated as the product of the ΔIns0-120/ΔGlu0-120 and the Matsuda index, where ΔIns0-120/ΔGlu0-120 represents the ratio of the incremental concentrations of insulin to those of glucose during the 0- to 120-min time periods under a 75-g oral glucose tolerance test. After MNT, HbA1c levels were reduced to 7.0 ± 1.0% (p < 0.001). The β-cell function was significantly improved (n = 13; p = 0.001; effect size d = 1.9). Fasting plasma glucose became below 7.0 mmol/l in 57% (8/13), and 120-minute plasma glucose became below 11.1 mmol/l in 43% (6/13). The β-cell function after MNT was significantly correlated with HbA1c levels achieved after MNT (Pearson's correlation coefficient r = -0.62, p = 0.025). In conclusion, the β-cell dysfunction was ameliorated after MNT without glucose-lowering pharmacotherapy in newly diagnosed type 2 diabetic outpatients who presented extreme hyperglycemia.