No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Can metformin be used as a treatment for unresponsive oral ulcers? A case report
Abstract
Introduction
Aphthae are common lesions that occur inside the mouth on the mucous membrane, often associated with various diseases. The causal pathogenesis generally depends on the accompanying condition, but there is usually no serious underlying cause.
Case presentation
This case report describes a 33-year-old male patient with a 10-year history of recurrent oral ulcers and impaired glucose tolerance. The patient had previously been treated with glucocorticoids, which provided temporary relief. Laboratory tests and immune profiles were normal. After 1 week of treatment with metformin at a dose of 500 mg twice daily, the lesions were relieved, and the patient required further metformin treatment for three years without any recurrence.
Discussion
Metformin has been shown to have anti-inflammatory effects in preclinical studies, making it a potential treatment option for mucocutaneous manifestations. This case report highlights the clinical effectiveness of metformin in treating oral ulcers and suggests its potential as an alternative treatment option for this condition.
Conclusion
Further studies are needed to confirm the efficacy and safety of metformin in treating mucocutaneous manifestations.
ResearchGate has not been able to resolve any citations for this publication.
Diabetes mellitus is defined by hyperglycemia resulting from impaired insulin action or distress, or both. Metformin is widely prescribed to control the disease and the most common adverse events caused by its use are diarrhea, nausea and/or abdominal discomfort. We evaluated the frequency profile of gastrointestinal adverse events associated with the use of metformin. This is a cross-sectional observational study, in which the occurrence of diarrhea in patients with type 2 diabetes mellitus who started treatment with metformin hydrochloride at a dose of 500 mg of prolonged release was reported. 12 (41.37%) participants were male and 17 (58.62%) were female. Diarrhea was present (n=16) in more than half of the patients (55.2%) who used the drug. Patients had an average of 12 episodes of diarrhea per month. There was also the presence of abdominal discomfort (n=7), in which 24.1% reported being very high. The study showed that the extended-release drug metformin hydrochloride 500 mg can cause gastrointestinal adverse events at the start of treatment and lasts for approximately twelve days.
Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also has a plethora of pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver. It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism in the cardiomyocytes, hence minimizing the cardiovascular risks. Its anticancer, antiproliferative and apoptosis-inducing effects on malignant cells might prove instrumental in the malignancy of organs like the breast, kidney, brain, ovary, lung, and endometrium. Preclinical studies have also shown some evidence of metformin’s neuroprotective role in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and Huntington’s disease. Metformin exerts its pleiotropic effects through varied pathways of intracellular signalling and exact mechanism in the majority of them remains yet to be clearly defined. This article has extensively reviewed the therapeutic benefits of metformin and the details of its mechanism for a molecule of boon in various conditions like diabetes, prediabetes, obesity, polycystic ovarian disease, metabolic derangement in HIV, various cancers and aging.
Metformin is among the most widely used antidiabetic drugs. Studies over the past few years have identified multiple novel molecular targets and pathways that metformin acts on to exert its beneficial effects in treating type 2 diabetes as well as other disorders involving dysregulated inflammation and redox homeostasis. In this mini-review, we discuss the latest cutting-edge research discoveries on novel molecular targets of metformin in glycemic control, cardiovascular protection, cancer intervention, anti-inflammation, antiaging, and weight control. Identification of these novel targets and pathways not only deepens our understanding of the molecular mechanisms by which metformin exerts diverse beneficial biological effects, but also provides opportunities for developing new mechanistically based drugs for human diseases.
Unlabelled:
Although central nervous system demyelinating lesions as a side effect of tumor necrosis factor (TNF)-alpha inhibitors have been reported, this treatment is still used in some autoimmune diseases.
Case presentation:
A 34-year-old Syrian male presented with difficulty walking and tingling, and numbness on the left side of his body over the next 4 days, during golimumab treatment. Over the past 2 months, fatigue, recurrent calf spasms, and extremity numbness were found. Sense disturbance and hyper-reflexes of the lower extremities were found on neurological examination. MRI demonstrated variant demyelinating lesions. Steroid therapy was initiated, and golimumab was discontinued, with good outcomes as the symptoms have disappeared.
Discussion:
The incidence of demyelination following anti-TNF therapy is uncommon. Most studies have reported that the average time between the anti-TNFα inhibitor treatment and the demyelinating lesion presence is from 5 months to 4 years, and these lesions may appear even after the cessation of the anti-TNFα inhibitor; meanwhile, a total cure of the symptoms after treatment cessation happened in our case, which suggests a causal relation, although a temporal relationship, in this case, cannot be established. The authors believe that golimumab plays a role in the demyelinating lesions development, although it may be a clinical manifestation during the course of Behcet's disease.
Conclusion:
Caution should be taken for the side effects of Golimumab treatment, such as demyelinating lesions, and long-term monitoring of patients with Bechet disease is required.
Background
Behçet's disease is a multisystem autoimmune disorder of unknown origin, characterized by frequent oral and genital ulcerations, ocular and cutaneous lesions, arthritis, and it may also involve the gastrointestinal, and central nervous system. In this paper we discuss a case of Behcet syndrome presenting with isolated oral aphthous initially and spotlight on the clinical features and treatment.
Case report
A case of a 32-year-old male with repetitive oral aphthous on the tongue and the inner cheeks for four days with a history of frequent recurrence. The patient responded to topical triamcinolone acetonide and 5–10 mg/day prednisone. Three weeks later, there was a recurrence of oral aphthous, genitalia lesions, and blurred vision with left eye redness. A uveitis diagnosis was made, and the patient was placed on 75mg (1mg/kg) prednisone with a resultant response. There was another recurrence with all the previous symptoms, so the decision with Dopson treatment was made. The patient was placed on Dapsone, resulting in complete resolution of the lesions with no reproduction within and after six months of several recall visits. The diagnosis of Bechet syndrome was made.
Discussion
Aphthous ulcers may be seen in a variety of disorders, while recurrent and persistent >6 weeks, individual non-healing ulcers require a review of the diagnosis. Behcet disease usually appears 2–3 years after oral and genital ulcers, but oral aphthae may be its first manifestation in 10–20% of cases. AS oral ulcers are among the common complaints of the polyclinics-patients, it is recommended to educate the health professionals to diagnose these unusual cases in the first instance, thus avoiding underdiagnosed and the time management to reduce complications and improve the quality of life in these patients.
Conclusion
A case of Behçet's disease in a 32-year-old male who presented initially with oral mucosa and later caused uveitis and genitalia aphthae.
Rheumatoid arthritis (RA) is one of more than 100 types of arthritis. This chronic autoimmune disorder affects the lining of synovial joints in about 0.5% of people and may induce severe joints deformity and disability. RA impacts health life of people from all sexes and ages with more prevalence in elderly and women people. Significant improvement has been noted in the last two decades revealing the mechanisms of the development of RA, the improvement of the early diagnosis and the development of new treatment options. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs) remain the most known treatments used against RA. However, not all patients respond well to these drugs and therefore, new solutions are of immense need to improve the disease outcomes. In the present review, we discuss and highlight the recent findings concerning the different classes of RA therapies including the conventional and modern drug therapies, as well as the recent emerging options including the phyto-cannabinoid and cell- and RNA-based therapies. A better understanding of their mechanisms and pathways might help find a specific target against inflammation, cartilage damage, and reduce side effects in arthritis.
Purpose of Review
To assess current management of Behcet’s disease (BD). Controversies on therapeutic approaches to different manifestations, whether conventional immunosuppressives (IS) or biologic agents, should be chosen, and options for refractory disease are discussed.
Recent Findings
Glucocorticoids are still the main agents for remission-induction and azathioprine the first-line conventional IS in maintenance phase to prevent relapses of major organ involvement. Apremilast is shown to be a safe and effective option approved by the FDA for oral ulcers. Large case series confirmed the efficacy and safety of TNFα inhibitors and Interferon-α. Promising results are observed with IL-1 inhibitors, ustekinumab, secukinumab, and tocilizumab for refractory BD.
Summary
Although both conventional IS and biologic agents are effectively used to suppress inflammation in BD, there is still an unmet need for clear therapeutic strategies in the management for different manifestations. Further controlled studies with new biologic agents, anticoagulants and the benefit of concomitant IS usage with biologics are needed to optimize the management of BD.
Metformin, one of the oldest oral antidiabetic agents and still recommended by almost all current guidelines as the first-line treatment for type 2 diabetes mellitus (T2DM), has become the medication with steadily increasing potential therapeutic indications. A broad spectrum of experimental and clinical studies showed that metformin has a pleiotropic activity and favorable effect in different pathological conditions, including prediabetes, type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM). Moreover, there are numerous studies, meta-analyses and population studies indicating that metformin is safe and well tolerated and may be associated with cardioprotective and nephroprotective effect. Recently, it has also been reported in some studies, but not all, that metformin, besides improvement of glucose homeostasis, may possibly reduce the risk of cancer development, inhibit the incidence of neurodegenerative disease and prolong the lifespan. This paper presents some arguments supporting the initiation of metformin in patients with newly diagnosed T2DM, especially those without cardiovascular risk factors or without established cardiovascular disease or advanced kidney insufficiency at the time of new guidelines favoring new drugs with pleotropic effects complimentary to glucose control. Moreover, it focuses on the potential beneficial effects of metformin in patients with T2DM and coexisting chronic diseases.
Introduction: The SCARE Guidelines were first published in 2016 and were last updated in 2018. They provide a structure for reporting surgical case reports and are used and endorsed by authors, journal editors and reviewers, in order to increase robustness and transparency in reporting surgical cases. They must be kept up to date in order to drive forwards reporting quality. As such, we have updated these guidelines via a DELPHI consensus exercise.
Methods: The updated guidelines were produced via a DELPHI consensus exercise. Members were invited from the previous DELPHI group, as well as editorial board member and peer reviewers of the International Journal of Surgery Case Reports. The expert group completed an online survey to indicate their agreement with proposed changes to the checklist items.
Results: 54 surgical experts agreed to participate and 53 (98%) completed the survey. The responses and suggested modifications were incorporated to the 2018 guideline. There was a high degree of agreement amongst the SCARE Group, with all SCARE Items receiving over 70% scores 7-9.
Conclusion: A DELPHI consensus exercise was completed, and an updated and improved SCARE Checklist is now presented.
Biguanides including metformin are drugs with a long history. They have been used to treat patients with type 2 diabetes since the 1960s. However, biguanides have not been widely used since the 1970s when one of the biguanides, phenformin, was found to cause lactic acidosis. The United Kingdom Prospective Diabetes Study (UKPDS) demonstrated that metformin not only had hypoglycemic action equivalent to sulfonylureas (SU) and insulin but also significantly lowered mortality and incidence of cardiovascular disease compared with SU or insulin treatment (1) while exerting a cardioprotective effect that lasted 10 years after the study ended (2). Metformin is also inexpensive. For these reasons, metformin is currently the first‐line drug in the A Consensus Report “Management of Hyperglycemia in Type 2 Diabetes” by the American Diabetes Association (ADA) / the European Association for the Study of Diabetes (EASD) (3).
Funding:
Boehringer Ingelheim Pharmaceuticals, Inc.
Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin–microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla, and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters. Our findings provide support for the notion that altered gut microbiota mediates some of metformin's antidiabetic effects.
Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance.
Objectives
Drug repositioning, that is, the use of a drug in an indication other than the one for which it was initially marketed, is a growing trend. Its origins lie mainly in the attrition experienced in recent years in the field of new drug discovery.
Key findings
Despite some regulatory and economic challenges, drug repositioning offers many advantages, and a number of recent successes have confirmed both its public health benefits and its commercial value. The first examples of successful drug repositioning mainly came about through serendipity like acetylsalicylic acid, thalidomide, sildenafil or dimethylfumarate.
Conclusion
The history of great‐repositioned drugs has given some solutions to various pathologies. Serendipity is not yet useful to find repositioning drugs. Drug repositioning is of growing interest. Nowadays, a more rational approach to the identification of drug candidates for repositioning is possible, especially using data mining.
Objective:
Behcet's disease (BD) is an autoimmune disorder that causes most commonly mouth and genital ulcerations and erythema nodules of the skin and currently has limited options of therapeutic medicines. Metformin is recently reported to suppress immune reaction, and we hypothesized that metformin could be an option for treatment of BD.
Methods:
Thirty patients with BD were enrolled in this perspective single-blinded, before-after study. We recorded the changes in the mucocutaneous activity index for BD (MAIBD), relapse frequency, C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) after metformin treatment to assess the changes in the disease activity. We also analyzed the changes in the protein and mRNA expression levels of Foxp3, interleukin-35 (IL-35), transforming growth factor-β (TGF-β), Ror-γt, IL-17, and tumor necrosis factor-α (TNF-α) in these patients using ELISA and qRT-PCR.
Results:
Of the 30 patients enrolled, 26 completed the trial. After the treatment, favorable responses were achieved in 88.46% (23/26) of the patients, and partial remission was obtained in 11.54% (4/26) of them. During the treatment, 8 patients complained of gastrointestinal side effects, for which 4 chose to withdraw from the study in the first week. Our results showed that metformin treatment decreased MAIBD and relapse frequency in the patients, and significantly lowered the clinical inflammatory indexes including CRP and ESR. The results of ELISA and qRT-PCR revealed that metformin treatment obviously increased Foxp3 and TGF-β expressions at both the protein and mRNA levels and significantly decreased the levels of ROR-γt, IL-17 and TNF-α as well as IL-35 level in these patients.
Conclusions:
Metformin treatment relieves the clinical symptoms, reduces the inflammatory reaction indexes and regulates the Treg/Th17 axis in patients with BD, suggesting the potential of metformin as a candidate medicine for treatment of BD.
Circulating autoantibodies and immune complex deposition are pathological hallmarks of systemic lupus erythematosus (SLE). B cell differentiation into plasma cells (PCs) and some T cell subsets that function as B cell helpers can be therapeutic targets of SLE. Mechanistic target of rapamycin (mTOR) signaling is implicated in the formation of B cells and germinal centers (GCs). We assessed the effect of metformin, which inhibits mTOR, on the development of autoimmunity using Roquin(san/san) mice. Oral administration of metformin inhibited the formation of splenic follicles and inflammation in kidney and liver tissues. It also decreased serum levels of anti-dsDNA Abs without affecting serum glucose levels. Moreover, metformin inhibited CD21(high)CD23(low) marginal zone B cells, B220(+)GL7(+) GC B cells, B220(-)CD138(+) PCs, and GC formation. A significant reduction in ICOS(+) follicular helper T cells was found in the spleens of the metformin-treated group compared with the vehicle-treated group. In addition, metformin inhibited Th17 cells and induced regulatory T cells. These alterations in B and T cell subsets by metformin were associated with enhanced AMPK expression and inhibition of mTOR-STAT3 signaling. Furthermore, metformin induced p53 and NF erythroid-2-related factor-2 activity in splenic CD4(+) T cells. Taken together, metformin-induced alterations in AMPK-mTOR-STAT3 signaling may have therapeutic value in SLE by inhibiting B cell differentiation into PCs and GCs.
Impaired glucose tolerance and impaired fasting glucose form an intermediate stage in the natural history of diabetes mellitus. From 10 to 15 percent of adults in the United States have one of these conditions. Impaired glucose tolerance is defined as two-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol) on the 75-g oral glucose tolerance test, and impaired fasting glucose is defined as glucose levels of 100 to 125 mg per dL (5.6 to 6.9 mmol per L) in fasting patients. These glucose levels are above normal but below the level that is diagnostic for diabetes. Patients with impaired glucose tolerance or impaired fasting glucose have a significant risk of developing diabetes and thus are an important target group for primary prevention. Risk factors for diabetes include family history of diabetes, body mass index greater than 25 kg per m2, sedentary lifestyle, hypertension, dyslipidemia, history of gestational diabetes or large-for-gestational-age infant, and polycystic ovary syndrome. Blacks, Latin Americans, Native Americans, and Asian-Pacific Islanders also are at increased risk for diabetes. Patients at higher risk should be screened with a fasting plasma glucose level. When the diagnosis of impaired glucose tolerance or impaired fasting glucose is made, physicians should counsel patients to lose 5 to 7 percent of their body weight and engage in moderate physical activity for at least 150 minutes per week. Drug therapy with metformin or acarbose has been shown to delay or prevent the onset of diabetes. However, medications are not as effective as lifestyle changes, and it is not known if treatment with these drugs is cost effective in the management of impaired glucose tolerance.
Therapeutic potentials of metformin in management of oral mucosal ulcer in rats: a histological study[J]
- Liang
Criteria for diagnosis of Behçet’s disease. International study group for Behcet’s disease
- Wechsler