-
Biomedicine & Pharmacotherapy =... Jun 2023Due to the strong association between diabetes and cancer incidents, several anti-diabetic drugs, including metformin, have been examined for their anticancer activity.... (Review)
Review
Due to the strong association between diabetes and cancer incidents, several anti-diabetic drugs, including metformin, have been examined for their anticancer activity. Metformin is a biguanide antihyperglycemic agent used as a first-line drug for type II diabetes mellitus. It exhibits anticancer activity by impacting different molecular pathways, such as AMP-inducible protein kinase (AMPK)-dependent and AMPK-independent pathways. Additionally, Metformin indirectly inhibits IGF-1R signaling, which is highly activated in breast malignancy. On the other hand, breast cancer is one of the major causes of cancer-related morbidity and mortality worldwide, where the human epidermal growth factor receptor-positive (HER2-positive) subtype is one of the most aggressive ones with a high rate of lymph node metastasis. In this review, we summarize the association between diabetes and human cancer, listing recent evidence of metformin's anticancer activity. A special focus is dedicated to HER2-positive breast cancer with regards to the interaction between HER2 and IGF-1R. Then, we discuss combination therapy strategies of metformin and other anti-diabetic drugs in HER2-positive breast cancer.
Topics: Humans; Female; Metformin; Breast Neoplasms; Diabetes Mellitus, Type 2; AMP-Activated Protein Kinases; Hypoglycemic Agents
PubMed: 37037091
DOI: 10.1016/j.biopha.2023.114676 -
Diabetes/metabolism Research and Reviews 2002This supplement focuses on the benefits of targeting insulin resistance through therapy with a new class of oral antidiabetic agents, the thiazolidinediones (TZDs) or... (Review)
Review
This supplement focuses on the benefits of targeting insulin resistance through therapy with a new class of oral antidiabetic agents, the thiazolidinediones (TZDs) or 'glitazones'. There are important differences between the three TZD class members that warrant discussion to enable physicians to make rational and informed therapeutic choices between the agents. Overall the TZDs appear to be similar in their effects on blood glucose, as all class members have demonstrated effective glycaemic control, both as monotherapy and in combination with sulphonylureas, metformin or exogenous insulin. The safety profiles of the three agents are more diverse, with what appear to be 'TZD class effects', (probably mediated via activation of peroxisome proliferator-activated receptor gamma [PPAR gamma]) and 'TZD-specific effects', which are unique to each agent and may be a consequence of differing chemical structures. While rosiglitazone and pioglitazone share some class effects with troglitazone, they have several characteristics that define them as unique agents. By tackling the control of type 2 diabetes through direct effects on insulin resistance, the TZDs represent an important new therapeutic tool for healthcare professionals.
Topics: Chromans; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Molecular Structure; Pioglitazone; Rosiglitazone; Thiazoles; Thiazolidinediones; Troglitazone
PubMed: 11921431
DOI: No ID Found -
Annals of Family Medicine 2010We conducted a study to examine the efficacy, effectiveness, and harms of pramlintide as adjunct therapy in adults and children with type 1 or type 2 diabetes. (Review)
Review
PURPOSE
We conducted a study to examine the efficacy, effectiveness, and harms of pramlintide as adjunct therapy in adults and children with type 1 or type 2 diabetes.
METHODS
We searched multiple bibliographic databases to January 2010, the US Food and Drug Administration Web site, and other sources to identify randomized controlled trials (RCTs) fulfilling inclusion criteria. Syntheses were qualitative because data were too heterogeneous for meta-analysis.
RESULTS
Three published RCTs in type 1 diabetes and 4 in type 2 disease fulfilled inclusion criteria. All trials were conducted with adults, and none was longer than 52 weeks. In type 1 diabetes with intensive insulin therapy, pramlintide was as effective as placebo in lowering glycated hemoglobin (HbA(1c)) levels in one trial. Pramlintide was somewhat more effective than placebo in patients using conventional insulin therapy, with a between-group difference in HbA(1c) levels of 0.2% to 0.3% (2 studies). In patients with type 2 diabetes, pramlintide was more effective at reducing HbA(1c) levels than placebo when added to flexibly dosed glargine (without prandial insulin) and when added to fixed-dose insulin therapies, with or without oral hypoglycemic agents (between-group differences in HbA(1c) were approximately 0.4%). Weight loss was observed with pramlintide in both type 1 and type 2 diabetes, whereas placebo-treated patients tended to gain weight. Pramlintide-treated patients experienced more frequent nausea and severe hypoglycemia compared with patients treated with placebo.
CONCLUSIONS
Pramlintide was somewhat more effective than placebo as adjunct therapy for improving HbA(1c) levels and weight in adults with type 1 diabetes on conventional insulin therapy, or type 2 diabetes and inadequate glycemic control with their current therapies, with between-group differences in HbA(1c) levels in the range of 0.2% to 0.4%. Further research is needed to determine pramlintide's durability of hypoglycemic effect, as well as effects on patient-reported outcomes, morbidity, mortality, and long-term harms.
Topics: Blood Glucose; Databases, Bibliographic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Islet Amyloid Polypeptide; Qualitative Research
PubMed: 21060125
DOI: 10.1370/afm.1174 -
International Journal of Molecular... Aug 2020Metformin, a synthetic derivative of guanidine, is commonly used as an oral antidiabetic agent and is considered a multi-vector application agent in the treatment of... (Review)
Review
Metformin, a synthetic derivative of guanidine, is commonly used as an oral antidiabetic agent and is considered a multi-vector application agent in the treatment of other inflammatory diseases. Recent studies have confirmed the beneficial effect of metformin on immune cells, with special emphasis on immunological mechanisms. Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by various clinical courses. Although the pathophysiology of MS remains unknown, it is most likely a combination of disturbances of the immune system and biochemical pathways with a disruption of blood-brain barrier (BBB), and it is strictly related to injury of intracerebral blood vessels. Metformin has properties which are greatly desirable for MS therapy, including antioxidant, anti-inflammatory or antiplatelet functions. The latest reports relating to the cardiovascular disease confirm an increased risk of ischemic events in MS patients, which are directly associated with a coagulation cascade and an elevated pro-thrombotic platelet function. Hence, this review examines the potential favourable effects of metformin in the course of MS, its role in preventing inflammation and endothelial dysfunction, as well as its potential antiplatelet role.
Topics: Animals; Clinical Trials as Topic; Hemostasis; Humans; Hypoglycemic Agents; Metformin; Multiple Sclerosis
PubMed: 32825027
DOI: 10.3390/ijms21175957 -
Seminars in Oncology Feb 2016Multiple epidemiologic studies have documented an association between the anti-diabetic agent metformin and reduced cancer incidence and mortality. However, this effect... (Review)
Review
Multiple epidemiologic studies have documented an association between the anti-diabetic agent metformin and reduced cancer incidence and mortality. However, this effect has not been consistently demonstrated in animal models or more recent epidemiological studies. The purpose of this paper is to examine metformin's chemopreventive potential by reviewing relevant mechanisms of action, preclinical evidence of efficacy, updated epidemiologic evidence after correction for potential biases and confounders, and recently completed and ongoing clinical trials. Although repurposing drugs with well described mechanisms of action and safety profiles is an appealing strategy for cancer prevention, there is no substitute for well executed late phase clinical trials to define efficacy and populations that are most likely to benefit from an intervention.
Topics: Animals; Anticarcinogenic Agents; Chemoprevention; Diabetes Mellitus; Drug Repositioning; Humans; Hypoglycemic Agents; Incidence; Metformin; Neoplasms; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 26970131
DOI: 10.1053/j.seminoncol.2015.09.009 -
Molecules (Basel, Switzerland) Jun 2020is a plant with high bioactive potential. It contains marrubiin, a labdane diterpene that is characteristic for this genus, as well as a complex mixture of phenolic... (Review)
Review
is a plant with high bioactive potential. It contains marrubiin, a labdane diterpene that is characteristic for this genus, as well as a complex mixture of phenolic compounds. According to numerous studies, acts as a good antioxidant agent, and due to this, it could potentially be useful in treatments of cancer, diabetes mellitus, and liver diseases. In addition, its anti-inflammatory, wound-healing, antihypertensive, hypolipidemic, and sedative potential are discussed. Apart from that, its antimicrobial activity, especially against Gram+ bacteria, fungi, herpes simplex virus, and parasites such as , , and was recorded. Additionally, it could be used as a chicken lice repellent, herbicide, and natural insecticide against mosquito larvae and natural molluscicide. In veterinary medicine, can be used as an anthelmintic against the eggs and larvae of bovine strongyles parasites, and as an antibiotic against bovine mastitis caused by resistant bacterial strains. Due to the mentioned benefits, there is a tendency for the cultivation of in order to ensure high-quality raw material, but more firm scientific evidence and well-designed clinical trials are necessary for the well-established use of herb and its preparations.
Topics: Animals; Anthelmintics; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Antioxidants; Biological Control Agents; Cattle; Cattle Diseases; Humans; Hypoglycemic Agents; Marrubium; Phytochemicals; Plants, Medicinal; Protective Agents; Wound Healing
PubMed: 32599693
DOI: 10.3390/molecules25122898 -
Molecules (Basel, Switzerland) Sep 2020Like in many developing countries, in Mexico, the use of medicinal plants is a common practice. Based on our own field experience, there are at least 800 plants used for... (Review)
Review
Like in many developing countries, in Mexico, the use of medicinal plants is a common practice. Based on our own field experience, there are at least 800 plants used for treating diabetes nowadays. Thus, their investigation is essential. In this context, this work aims to provide a comprehensive and critical review of the molecules isolated from Mexican hypoglycemic plants, including their source and target tested. In the last few years, some researchers have focused on the study of Mexican hypoglycemic plants. Most works describe the hypoglycemic effect or the mechanism of action of the whole extract, as well as the phytochemical profile of the tested extract. Herein, we analyzed 85 studies encompassing 40 hypoglycemic plants and 86 active compounds belonging to different classes of natural products: 28 flavonoids, 25 aromatic compounds, other than flavonoids, four steroids, 23 terpenoids, 4 oligosaccharides, and 1 polyalcohol. These compounds have shown to inhibit α-glucosidases, increase insulin secretion levels, increase insulin sensitivity, and block hepatic glucose output. Almost half of these molecules are not common metabolites, with a narrow taxonomic distribution, which makes them more interesting as lead molecules. Altogether, this analysis provides a necessary inventory useful for future testing of these active molecules against different hypoglycemic targets, to get a better insight into the already described mechanisms, and overall, to contribute to the knowledge of Mexican medicinal plants.
Topics: Animals; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Insulin Secretion; Medicine, Traditional; Mexico; Molecular Structure; Phytochemicals; Plant Extracts; Plants, Medicinal; alpha-Glucosidases
PubMed: 32927754
DOI: 10.3390/molecules25184145 -
Diabetes/metabolism Research and Reviews Feb 2019Persons with type 1 or type 2 diabetes have a significantly higher fracture risk than age-matched persons without diabetes, attributed to disease-specific deficits in... (Review)
Review
Persons with type 1 or type 2 diabetes have a significantly higher fracture risk than age-matched persons without diabetes, attributed to disease-specific deficits in the microarchitecture and material properties of bone tissue. Therefore, independent effects of diabetes drugs on skeletal integrity are vitally important. Studies of incretin-based therapies have shown divergent effects of different agents on fracture risk, including detrimental, beneficial, and neutral effects. The sulfonylurea class of drugs, owing to its hypoglycemic potential, is thought to amplify the risk of fall-related fractures, particularly in the elderly. Other agents such as the biguanides may, in fact, be osteo-anabolic. In contrast, despite similarly expected anabolic properties of insulin, data suggests that insulin pharmacotherapy itself, particularly in type 2 diabetes, may be a risk factor for fracture, negatively associated with determinants of bone quality and bone strength. Finally, sodium-dependent glucose co-transporter 2 inhibitors have been associated with an increased risk of atypical fractures in select populations, and possibly with an increase in lower extremity amputation with specific SGLT2I drugs. The role of skeletal muscle, as a potential mediator and determinant of bone quality, is also a relevant area of exploration. Currently, data regarding the impact of glucose lowering medications on diabetes-related muscle atrophy is more limited, although preclinical studies suggest that various hypoglycemic agents may have either aggravating (sulfonylureas, glinides) or repairing (thiazolidinediones, biguanides, incretins) effects on skeletal muscle atrophy, thereby influencing bone quality. Hence, the therapeutic efficacy of each hypoglycemic agent must also be evaluated in light of its impact, alone or in combination, on musculoskeletal health, when determining an individualized treatment approach. Moreover, the effect of newer medications (potentially seeking expanded clinical indication into the pediatric age range) on the growing skeleton is largely unknown. Herein, we review the available literature regarding effects of diabetes pharmacotherapy, by drug class and/or by clinical indication, on the musculoskeletal health of persons with diabetes.
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Musculoskeletal System
PubMed: 30467957
DOI: 10.1002/dmrr.3100 -
British Journal of Pharmacology Feb 2022Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has undergone a revolutionary turnaround from discovery to clinically approved therapeutic. Rapid progress in... (Review)
Review
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has undergone a revolutionary turnaround from discovery to clinically approved therapeutic. Rapid progress in drug design and formulation has led from initial development of short- and long-acting drugs suitable for daily or weekly parenteral administration, respectively, through to the most recent approval of an orally active GLP-1 agent. The current review outlines the biological action profile of GLP-1 including the various beneficial metabolic responses in pancreatic and extra-pancreatic tissues, including the gastrointestinal tract, liver, bone and kidney as well as the reproductive cardiovascular and CNS. We then briefly consider clinically approved GLP-1 receptor ligands and recent advances in this field. Given the sustained evolution in the area of GLP-1 drug development and excellent safety profile, as well as the plethora of metabolic benefits, clinical approval for use in diseases beyond diabetes and obesity is very much conceivable. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.
Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Heart; Humans; Hypoglycemic Agents; Ligands; Obesity
PubMed: 33822370
DOI: 10.1111/bph.15485 -
Biological & Pharmaceutical Bulletin 2022We studied the effect of dietary fibers (DFs) on the levels of free hypoglycemic agents in vitro, i.e., glimepiride and the biguanides buformin and metformin. The levels...
We studied the effect of dietary fibers (DFs) on the levels of free hypoglycemic agents in vitro, i.e., glimepiride and the biguanides buformin and metformin. The levels of free buformin and free metformin were not affected by mixtures of DFs, i.e., cellulose, chitosan, pectin (PE), and glucomannan (GM), in fluids of pH 1.2 and 6.8 (similar to the pH of the stomach and intestines, respectively). However, the free biguanide level was significantly reduced by mixing with PE or sodium alginate (AL), in water. The free glimepiride level was reduced in the mixture of AL, PE, and GM (in a solution with a pH of 6.8). The changes in aqueous AL solution pH seemed to reflect the free metformin levels. Therefore, the effects of DFs on free drug levels were dependent on drug type, hypoglycemic agent, and mixing solution. In this study, the oral regimen concentrations of the drug and DFs were used. Based on these results, it is important to consider the interactions between hypoglycemic agents and DFs.
Topics: Hypoglycemic Agents; Buformin; Metformin; Dietary Fiber
PubMed: 36328507
DOI: 10.1248/bpb.b22-00385