RESUMO
BACKGROUND: Lifestyle changes, especially regarding diet quality and physical activity, are important in the management of type 2 diabetes (T2D). This mixed-methods study explores self-initiated lifestyle changes in patients with T2D who followed a periodic fasting-mimicking diet (FMD). METHODS: Quantitative data were obtained from the Fasting In diabetes Treatment trial (November 2018 to August 2021) in which 100 participants with T2D, using metformin only or no medication, were randomised to receive a monthly 5-day FMD for twelve months next to usual care, or usual care only. Diet quality and physical activity questionnaires were completed at baseline, six and twelve months. Changes over time were analysed using linear mixed models. Focus groups were organized with FMD participants to explore experiences regarding self-initiated lifestyle changes. The qualitative data was analysed using the Theoretical Domains Framework. RESULTS: Questionnaires were available from 49 FMD participants and 43 controls. No differences in diet quality were found. Total physical activity in the FMD participants changed from 34.6 to 38.5 h per week (h/wk) from baseline to twelve months, while in controls it changed from 34.9 to 29.0 h/wk (between group difference, p = 0.03). In six focus groups with FMD participants (n = 20), individual participants perceived the FMD as an encouragement for (minor) lifestyle changes. There were no barriers to behaviour change related to the FMD. Important facilitators of healthy behaviour were an increase in awareness of the impact of lifestyle on health (knowledge), better physical fitness (physical) and health improvement (reinforcement). Facilitators unrelated to the FMD included family support (social influences) and opportunities in the neighbourhood (environmental context and resources), while barriers unrelated to the FMD were experiencing health problems (physical) and social events (social influences). CONCLUSIONS: Using an FMD for five consecutive days per month did not affect diet quality in between FMD periods in quantitative analysis, but increased the number of hours per week spent on physical activity. Qualitative analysis revealed self-initiated improvements in both diet quality and physical activity in individual participants using an FMD. Healthcare professionals could use an FMD programme as a 'teachable moment' to stimulate additional lifestyle changes. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03811587. Registered 22 January 2019.
Assuntos
Diabetes Mellitus Tipo 2, Exercício Físico, Jejum, Humanos, Diabetes Mellitus Tipo 2/dietoterapia, Diabetes Mellitus Tipo 2/psicologia, Masculino, Feminino, Pessoa de Meia-Idade, Jejum/fisiologia, Exercício Físico/fisiologia, Exercício Físico/psicologia, Idoso, Estilo de Vida, Grupos Focais, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Metformina/uso terapêutico, Dieta, Inquéritos e QuestionáriosRESUMO
PURPOSE: This study was undertaken to evaluate the potential risk of acute pancreatitis with empagliflozin in patients with type 2 diabetes (T2D) newly initiating empagliflozin. METHODS: Data from two large US claims databases were analyzed in an observational study of patients with T2D receiving metformin who were newly prescribed empagliflozin versus sulfonylurea (SU). Because dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have been associated with the risk of acute pancreatitis in some studies, patients on these agents were excluded. Using pooled analyses of data from the two databases (2014-2021), patients initiating empagliflozin were matched 1:1 within database to patients initiating SU using propensity scores (PS) that incorporated relevant demographic and clinical characteristics. Prespecified sensitivity analyses were performed for design parameters. RESULTS: The analyses identified 72 661 new users of empagliflozin and 422 018 new users of SUs, with both patient groups on concurrent metformin therapy. Baseline characteristics within treatment groups appeared to be similar across the 72 621 matched pairs. After mean follow-up of ~6 months, incidence rates of acute pancreatitis in the pooled matched cohort were 10.30 (95% confidence interval [CI] 9.29-11.39) events per 1000 patient-years (PY) for empagliflozin and 11.65 (95% CI 10.59-12.77) events per 1000 PY for SUs. On a background of metformin, patients newly initiating empagliflozin did not have an increased risk of acute pancreatitis compared with those initiating an SU (pooled PS matched hazard ratio 0.88 [0.76-1.02]) across 75621.42 PY of follow-up. CONCLUSIONS: The results of this voluntary post-approval safety study provide additional evidence that the use of empagliflozin for the treatment of T2D is not associated with an increased risk of acute pancreatitis.
Assuntos
Compostos Benzidrílicos, Diabetes Mellitus Tipo 2, Glucosídeos, Metformina, Pancreatite, Compostos de Sulfonilureia, Humanos, Compostos Benzidrílicos/efeitos adversos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/epidemiologia, Pancreatite/induzido quimicamente, Pancreatite/epidemiologia, Glucosídeos/efeitos adversos, Glucosídeos/uso terapêutico, Glucosídeos/administração & dosagem, Compostos de Sulfonilureia/efeitos adversos, Compostos de Sulfonilureia/uso terapêutico, Masculino, Feminino, Pessoa de Meia-Idade, Idoso, Metformina/efeitos adversos, Metformina/administração & dosagem, Metformina/uso terapêutico, Hipoglicemiantes/efeitos adversos, Hipoglicemiantes/administração & dosagem, Bases de Dados Factuais, Incidência, Vigilância de Produtos Comercializados/estatística & dados numéricos, Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Adulto, Estados Unidos/epidemiologia, Pontuação de PropensãoRESUMO
INTRODUCTION: There has been increasing evidence that the gut microbiota is closely related to type 2 diabetes (T2D). Metformin (Met) is often used in combination with saxagliptin (Sax) and repaglinide (Rep) for the treatment of T2D. However, little is known about the effects of these combination agents on gut microbiota in T2D. RESEARCH DESIGN AND METHODS: A T2D mouse model induced by a high-fat diet (HFD) and streptozotocin (STZ) was employed. The T2D mice were randomly divided into six groups, including sham, Met, Sax, Rep, Met+Sax and Met+Rep, for 4 weeks. Fasting blood glucose level, serum biochemical index, H&E staining of liver, Oil red O staining of liver and microbiota analysis by 16s sequencing were used to access the microbiota in the fecal samples. RESULTS: These antidiabetics effectively prevented the development of HFD/STZ-induced high blood glucose, and the combination treatment had a better effect in inhibiting lipid accumulation. All these dosing regimens restored the decreasing ratio of the phylum Bacteroidetes: Firmicutes, and increasing abundance of phylum Desulfobacterota, expect for Met. At the genus level, the antidiabetics restored the decreasing abundance of Muribaculaceae in T2D mice, but when Met was combined with Rep or Sax, the abundance of Muribaculaceae was decreased. The combined treatment could restore the reduced abundance of Prevotellaceae_UCG-001, while Met monotherapy had no such effect. In addition, the reduced Lachnospiraceae_NK4A136_group was well restored in the combination treatment groups, and the effect was much greater than that in the corresponding monotherapy group. Therefore, these dosing regimens exerted different effects on the composition of gut microbiota, which might be associated with the effect on T2D. CONCLUSIONS: Supplementation with specific probiotics may further improve the hypoglycemic effects of antidiabetics and be helpful for the development of new therapeutic drugs for T2D.
Assuntos
Adamantano, Glicemia, Carbamatos, Diabetes Mellitus Experimental, Diabetes Mellitus Tipo 2, Dieta Hiperlipídica, Dipeptídeos, Microbioma Gastrointestinal, Hipoglicemiantes, Metformina, Piperidinas, Animais, Microbioma Gastrointestinal/efeitos dos fármacos, Metformina/farmacologia, Metformina/uso terapêutico, Camundongos, Dieta Hiperlipídica/efeitos adversos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/microbiologia, Hipoglicemiantes/farmacologia, Hipoglicemiantes/uso terapêutico, Diabetes Mellitus Experimental/tratamento farmacológico, Carbamatos/farmacologia, Dipeptídeos/farmacologia, Masculino, Adamantano/análogos & derivados, Adamantano/farmacologia, Adamantano/uso terapêutico, Piperidinas/farmacologia, Piperidinas/uso terapêutico, Glicemia/análise, Glicemia/efeitos dos fármacos, Camundongos Endogâmicos C57BL, Quimioterapia Combinada, EstreptozocinaRESUMO
BACKGROUND: Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. CASE PRESENTATION: A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. CONCLUSIONS: M-B enema and suppository may be an effective treatment for chronic RP.
Assuntos
Enema, Metformina, Proctite, Neoplasias da Próstata, Lesões por Radiação, Humanos, Masculino, Proctite/tratamento farmacológico, Proctite/etiologia, Idoso, Metformina/uso terapêutico, Metformina/administração & dosagem, Neoplasias da Próstata/radioterapia, Neoplasias da Próstata/tratamento farmacológico, Lesões por Radiação/tratamento farmacológico, Doença Crônica, Resultado do Tratamento, Butiratos/uso terapêutico, Hemorragia Gastrointestinal/tratamento farmacológico, Hemorragia Gastrointestinal/terapia, Hemorragia Gastrointestinal/etiologia, SupositóriosRESUMO
OBJECTIVE: To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice. DESIGN: Cohort study emulating a comparative effectiveness trial (target trial). SETTING: Linked primary care, hospital, and death data in England, 2015-21. PARTICIPANTS: 75 739 adults with type 2 diabetes mellitus who initiated second line oral antidiabetic treatment with a sulfonylurea, DPP-4 inhibitor, or SGLT-2 inhibitor added to metformin. MAIN OUTCOME MEASURES: Primary outcome was absolute change in glycated haemoglobin A1c (HbA1c) between baseline and one year follow-up. Secondary outcomes were change in body mass index (BMI), systolic blood pressure, and estimated glomerular filtration rate (eGFR) at one year and two years, change in HbA1c at two years, and time to ≥40% decline in eGFR, major adverse kidney event, hospital admission for heart failure, major adverse cardiovascular event (MACE), and all cause mortality. Instrumental variable analysis was used to reduce the risk of confounding due to unobserved baseline measures. RESULTS: 75 739 people initiated second line oral antidiabetic treatment with sulfonylureas (n=25 693, 33.9%), DPP-4 inhibitors (n=34 464 ,45.5%), or SGLT-2 inhibitors (n=15 582, 20.6%). SGLT-2 inhibitors were more effective than DPP-4 inhibitors or sulfonylureas in reducing mean HbA1c values between baseline and one year. After the instrumental variable analysis, the mean differences in HbA1c change between baseline and one year were -2.5 mmol/mol (95% confidence interval (CI) -3.7 to -1.3) for SGLT-2 inhibitors versus sulfonylureas and -3.2 mmol/mol (-4.6 to -1.8) for SGLT-2 inhibitors versus DPP-4 inhibitors. SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in reducing BMI and systolic blood pressure. For some secondary endpoints, evidence for SGLT-2 inhibitors being more effective was lacking-the hazard ratio for MACE, for example, was 0.99 (95% CI 0.61 to 1.62) versus sulfonylureas and 0.91 (0.51 to 1.63) versus DPP-4 inhibitors. SGLT-2 inhibitors had reduced hazards of hospital admission for heart failure compared with DPP-4 inhibitors (0.32, 0.12 to 0.90) and sulfonylureas (0.46, 0.20 to 1.05). The hazard ratio for a ≥40% decline in eGFR indicated a protective effect versus sulfonylureas (0.42, 0.22 to 0.82), with high uncertainty in the estimated hazard ratio versus DPP-4 inhibitors (0.64, 0.29 to 1.43). CONCLUSIONS: This emulation study of a target trial found that SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in lowering mean HbA1c, BMI, and systolic blood pressure and in reducing the hazards of hospital admission for heart failure (v DPP-4 inhibitors) and kidney disease progression (v sulfonylureas), with no evidence of differences in other clinical endpoints.
Assuntos
Diabetes Mellitus Tipo 2, Inibidores da Dipeptidil Peptidase IV, Hemoglobinas Glicadas, Hipoglicemiantes, Metformina, Inibidores do Transportador 2 de Sódio-Glicose, Compostos de Sulfonilureia, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Masculino, Feminino, Pessoa de Meia-Idade, Compostos de Sulfonilureia/uso terapêutico, Compostos de Sulfonilureia/administração & dosagem, Idoso, Metformina/uso terapêutico, Metformina/administração & dosagem, Hemoglobinas Glicadas/análise, Hemoglobinas Glicadas/metabolismo, Inibidores da Dipeptidil Peptidase IV/uso terapêutico, Inibidores da Dipeptidil Peptidase IV/administração & dosagem, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem, Administração Oral, Taxa de Filtração Glomerular/efeitos dos fármacos, Inglaterra/epidemiologia, Quimioterapia Combinada, Resultado do Tratamento, Estudos de Coortes, Pesquisa Comparativa da Efetividade, Índice de Massa Corporal, Pressão Sanguínea/efeitos dos fármacosRESUMO
Memory issues are a prevalent symptom in different neurodegenerative diseases and can also manifest in certain psychiatric conditions. Despite limited medications approved for treating memory problems, research suggests a lack of sufficient options in the market. Studies indicate that a significant percentage of elderly individuals experience various forms of memory disorders. Metformin, commonly prescribed for type 2 diabetes, has shown neuroprotective properties through diverse mechanisms. This study explores the potential of metformin in addressing memory impairments. The current research gathered its data by conducting an extensive search across electronic databases including PubMed, Web of Science, Scopus, and Google Scholar. Previous research suggests that metformin enhances brain cell survival and memory function in both animal and clinical models by reducing oxidative stress, inflammation, and cell death while increasing beneficial neurotrophic factors. The findings of the research revealed that metformin is an effective medication for enhancing various types of memory problems in numerous studies. Given the rising incidence of memory disorders, it is plausible to utilize metformin, which is an affordable and accessible drug. It is often recommended as a treatment to boost memory.
Assuntos
Transtornos da Memória, Metformina, Metformina/uso terapêutico, Metformina/farmacologia, Transtornos da Memória/tratamento farmacológico, Humanos, Animais, Estresse Oxidativo/efeitos dos fármacos, Fármacos Neuroprotetores/uso terapêutico, Fármacos Neuroprotetores/farmacologia, Memória/efeitos dos fármacos, Hipoglicemiantes/farmacologia, Hipoglicemiantes/uso terapêutico, Encéfalo/efeitos dos fármacos, Encéfalo/metabolismoRESUMO
BACKGROUND: The efficacy and safety of lobeglitazone sulfate has been reported only in the Korean population, and no study has been conducted in India. MATERIALS AND METHODS: In this 16-week randomized, double-blind, and multicenter study, the efficacy and safety of lobeglitazone sulfate 0.5 mg were evaluated with pioglitazone 15 mg. Type 2 diabetes mellitus (T2DM) patients with ≥7.5% glycated hemoglobin (HbA1c) ≤10.5% and on stable metformin dose were assigned to both treatment arms. The primary outcome was a mean change in HbA1c. Safety assessments included adverse events (AE), home-based glucose monitoring, vital parameters, electrocardiogram (ECG), and laboratory assessments. RESULTS: A total of 328 subjects were randomized equally in two groups. A statistically significant reduction in HbA1c at week 16 in the lobeglitazone group with the least square (LS) mean change: 1.01 [standard error (SE): 0.09] (p < 0.0001) was seen. The LS mean difference between the two groups was 0.05 (SE: 0.12) [95% confidence interval (CI): -0.18, 0.27], which was statistically significant (p = 0.0013). Statistically significant reductions were also observed in fasting and postprandial glucose. Treatment-emergent Aes (TEAE) were comparable between both groups. CONCLUSION: Lobeglitazone 0.5 mg once daily was found to be efficacious and safe in the treatment of T2DM in the Indian population. Lobeglitazone significantly improved glycemic parameters and was noninferior to pioglitazone; hence, it could be a promising insulin sensitizer in T2DM management in India.
Assuntos
Diabetes Mellitus Tipo 2, Quimioterapia Combinada, Hemoglobinas Glicadas, Hipoglicemiantes, Metformina, Pioglitazona, Tiazolidinedionas, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Metformina/uso terapêutico, Metformina/administração & dosagem, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Hipoglicemiantes/efeitos adversos, Masculino, Pessoa de Meia-Idade, Método Duplo-Cego, Feminino, Tiazolidinedionas/uso terapêutico, Tiazolidinedionas/administração & dosagem, Hemoglobinas Glicadas/análise, Índia, Pioglitazona/uso terapêutico, Pioglitazona/administração & dosagem, Glicemia/análise, Glicemia/efeitos dos fármacos, Adulto, Resultado do Tratamento, Idoso, PirimidinasRESUMO
Obesity treatment is often burdensome for patients. We used the combination of moderate caloric restriction (CR) with hypoglycemic metformin to assess their multidirectional effect in obese patients. One group was treated only with moderate CR (n=21) the second was treated with moderate CR and 800 mg metformin twice daily (n=23). Serum was drawn before and after treatment. The following parameters were monitored: anthropometric, cardiovascular, inflammatory, metabolic, and markers characteristic for thyroid, liver, pancreas, and kidney functions. Both tested groups did not significantly differ in most tested parameters after the treatment. Two groups reduced anthropometric parameters (body mass, body mass index (BMI), waist circumference) and fat mass but also muscle and fat-free mass, improving systolic blood pressure, insulin and leptin concentration, insulin sensitivity, leptin to adiponectin ratio, and inflammatory markers. Unfortunately, there was little impact on improving dyslipidemia and the thyroid and liver parameters. Free triiodothyronine (fT3) and gamma glutamyl transferase (GGT) activity were decreased in both groups, but triglycerides were reduced only in patients treated with moderate CR. Metformin with CR treatment decreases uric acid and aspartate aminotransferase (AspAT) activity. Metformin treatment with moderate CR in obese patients mainly improved insulin sensitivity, resulting in a reduction of patients with glucose intolerance, improved anthropometric, cardiovascular, and inflammatory mediators, and only slightly enhanced liver and thyroid function. No changes in kidney and pancreas function were observed during the treatment. In conclusion, eight weeks of CR alone and CR with metformin in obese adults improved anthropometric and metabolic markers, reduced muscle mass, fT3, GGT, proinflammatory, and CV parameters, and displayed no changes in kidney and pancreas function. The group treated with metformin after the treatment was still more obese and had higher C-reactive protein (CRP) and homeostasis model assessment-an index of insulin resistance (HOMA-IR), but despite this, considerably reduced the number of patients with glucose intolerance.
Assuntos
Restrição Calórica, Hipoglicemiantes, Metformina, Obesidade, Humanos, Metformina/uso terapêutico, Obesidade/tratamento farmacológico, Obesidade/sangue, Obesidade/metabolismo, Restrição Calórica/métodos, Masculino, Feminino, Adulto, Pessoa de Meia-Idade, Hipoglicemiantes/uso terapêutico, Resistência à InsulinaRESUMO
AIM: To investigate the factors affecting metformin concentrations after chronic administration in patients with polycystic ovary syndrome (PCOS), focusing on the pharmacokinetic variability and its implications for personalized therapy. METHODS: This study enrolled 53 PCOS patients undergoing long-term metformin treatment at the Clinic for Gynecology and Obstetrics in Nis, Serbia, from February to December 2019. Pharmacokinetic parameters were measured from blood samples, and metformin concentrations were determined with validated analytical techniques. RESULTS: There was a significant variability in metformin concentrations among PCOS patients, with body mass index (BMI) identified as a major influencing factor. Higher BMI was associated with lower plasma metformin levels, a finding suggesting an altered pharmacokinetic profile in obese patients. CONCLUSIONS: This study highlights the critical role of BMI in influencing metformin pharmacokinetics in PCOS patients and underscores the need for personalized treatment strategies in patients with PCOS.
Assuntos
Índice de Massa Corporal, Hipoglicemiantes, Metformina, Síndrome do Ovário Policístico, Humanos, Síndrome do Ovário Policístico/tratamento farmacológico, Síndrome do Ovário Policístico/sangue, Metformina/farmacocinética, Metformina/sangue, Metformina/administração & dosagem, Metformina/uso terapêutico, Feminino, Adulto, Hipoglicemiantes/farmacocinética, Hipoglicemiantes/sangue, Hipoglicemiantes/uso terapêutico, Sérvia, Adulto Jovem, ObesidadeRESUMO
BACKGROUND: Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets that are currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. A levonorgestrel intrauterine device may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed. Metformin, a drug that is often used to treat people with diabetes, has been shown, in some human studies, to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain. This is an update of a review first published in 2017. OBJECTIVES: To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, PubMed, Embase, Google Scholar, OpenGrey, LILACS, and two trials registers from inception to 5 September 2022. We searched the bibliographies of all relevant studies, and contacted experts in the field for any additional trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cross-over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo, no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, extracted data from included studies, assessed the risk of bias in the included studies, and assessed the certainty of the evidence for each outcome. We resolved disagreements by discussion or by deferring to a third review author. When study details were missing, review authors contacted the study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. MAIN RESULTS: We included seven RCTs, in which a total of 387 women took part. In the comparison, Metformin plus megestrol versus megestrol alone, we rated the certainty of the evidence as low for the outcome, regression of endometrial hyperplasia. We rated the quality of the evidence as very low for the rest of the outcomes, in all three comparisons. Although there was a low risk of selection bias, there was a high risk of bias in the blinding of personnel and outcome assessment (performance bias and detection bias) in many studies. This update identified four new RCTs and six ongoing RCTs. Metformin versus megestrol We are uncertain whether metformin increases the regression of endometrial hyperplasia towards normal histology over megestrol (odds ratio (OR) 4.89, 95% confidence interval (CI) 1.56 to 15.32; P = 0.006; 2 RCTs, 83 participants; I² = 7%; very low-certainty evidence). This evidence suggests that if the rate of regression with megestrol is 61%, the rate of regression with metformin would be between 71% and 96%. It is unresolved whether metformin results in different rates of abnormal uterine bleeding or hysterectomy compared to megestrol. No study in this comparison reported progression of hyperplasia to endometrial cancer, recurrence of endometrial hyperplasia, health-related quality of life, or adverse effects during treatment. Metformin plus megestrol versus megestrol monotherapy The combination of metformin and megestrol may enhance the regression of endometrial hyperplasia towards normal histology more than megestrol alone (OR 3.27, 95% CI 1.65 to 6.51; P = 0.0007; 4 RCTs, 258 participants; I² = 0%, low-certainty evidence). This suggests that if the rate of regression with megestrol monotherapy is 54%, the rate of regression with the addition of metformin would be between 66% and 84%. In one study, 3/8 (37.5%) of participants who took metformin had nausea that settled without further treatment. It is unresolved whether the combination of metformin and megestrol results in different rates of recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, or hysterectomy compared to megestrol monotherapy. No study in this comparison reported abnormal uterine bleeding, or health-related quality of life. Metformin plus levonorgestrel (intrauterine system) versus levonorgestrel (intrauterine system) monotherapy We are uncertain whether there is a difference between groups in the regression of endometrial hyperplasia towards normal histology (OR 0.29, 95% CI 0.01 to 7.56; 1 RCT, 46 participants; very low-certainty evidence). This evidence suggests that if the rate of regression with levonorgestrel monotherapy is 96%, the rate of regression with the addition of metformin would be between 73% and 100%. It is unresolved whether the combination of metformin and levonorgestrel results in different rates of abnormal uterine bleeding, hysterectomy, or the development of adverse effects during treatment compared to levonorgestrel monotherapy. No study in this comparison reported recurrence of endometrial hyperplasia, progression of hyperplasia to endometrial cancer, or health-related quality of life. AUTHORS' CONCLUSIONS: Review authors found insufficient evidence to either support or refute the use of metformin, specifically megestrol acetate, given alone or in combination with standard therapy, for the treatment of women with endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials, yielding long-term outcome data are still needed to address this clinical question.
Assuntos
Hiperplasia Endometrial, Metformina, Ensaios Clínicos Controlados Aleatórios como Assunto, Humanos, Metformina/uso terapêutico, Feminino, Hiperplasia Endometrial/tratamento farmacológico, Hipoglicemiantes/uso terapêuticoRESUMO
Sodium-glucose co-transporters type 2 inhibitors (SLGT2i) are highly effective in controlling type 2 diabetes, but reported beneficial cardiovascular effects suggest broader actions on insulin resistance. Weight loss may be initially explained by glycosuria-induced net caloric output and secondary volumetric reduction, but its maintenance could be due to loss of visceral fat mass. Structured ultrasound (US) imaging of abdominal adipose tissue ("eco-obesity") is a recently described methodology used to measure 5 consecutive layers of abdominal fat, not assessable by DEXA or CT scan: superficial subcutaneous (SS), deep subcutaneous (DS), preperitoneal (PP), omental (Om) and right perirenal (RK). PP, Om and RK are predictors of metabolic syndrome (MS) with defined cut-off points. To assess the effect of SLGT2i on every fat depot we enrolled 29 patients with type 2 Diabetes (HbA1c 6.5-9%) and Obesity (IMC > 30 kg/m2) in an open-label, randomized, phase IV trial (EudraCT: 2019-000979-16): the Omendapa trial. Diabetes was diagnosed < 12 months before randomization and all patients were treatment naïve. 14 patients were treated with metformin alone (cohort A) and 15 were treated with metformin + dapaglifozin (cohort B). Anthropometric measures and laboratory tests for glucose, lipid profile, insulin, HOMA, leptin, ultrasensitive-CRP and microalbuminuria (MAL) were done at baseline, 3rd and 6th months. At 6th month, weight loss was -5.5 ± 5.2 kg (5.7% from initial weight) in cohort A and -8.4 ± 4.4 kg (8.6%) in cohort B. Abdominal circumference showed a -2.7 ± 3.1 cm and -5.4 ± 2.5 cm reduction, respectively (p = 0.011). Both Metformin alone (-19.4 ± 20.1 mm; -21.7%) or combined with Dapaglifozin (-20.5 ± 19.4 mm; -21.8%) induced significant Om fat reduction. 13.3% of cohort A patients and 21.4% of cohort's B reached Om thickness below the cut-off for MS criteria. RK fat loss was significantly greater in cohort B group compared to cohort A, at both kidneys. Only in the Met + Dapa group, we observed correlations between Om fat with leptin/CRP/MAL and RK fat with HOMA-IR. US is a useful clinical tool to assess ectopic fat depots. Both Metformin and Dapaglifozin induce fat loss in layers involved with MS but combined treatment is particularly effective in perirenal fat layer reduction. Perirenal fat should be considered as a potential target for cardiovascular dapaglifozin beneficial effects.
Assuntos
Compostos Benzidrílicos, Diabetes Mellitus Tipo 2, Glucosídeos, Metformina, Obesidade, Humanos, Metformina/uso terapêutico, Metformina/farmacologia, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/complicações, Diabetes Mellitus Tipo 2/metabolismo, Glucosídeos/uso terapêutico, Glucosídeos/farmacologia, Feminino, Masculino, Obesidade/tratamento farmacológico, Obesidade/complicações, Pessoa de Meia-Idade, Compostos Benzidrílicos/uso terapêutico, Compostos Benzidrílicos/farmacologia, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Inibidores do Transportador 2 de Sódio-Glicose/farmacologia, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/farmacologia, Idoso, Quimioterapia Combinada, AdultoRESUMO
Heart failure (HF) remains a significant problem for healthcare systems, requiring the use of intervention and multimodal management strategies. We aimed to assess the short-term effect of empagliflozin (EMPA) and metformin on cardiac function parameters, including ventricular dimension-hypertrophy, septal thickness, ejection fraction (EF), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with HF and mildly reduced EF. A case-control study included 60 newly diagnosed patients with HF. Patients were divided into two groups: Group E received standard HF treatment (carvedilol, bumetanide, sacubitril-valsartan, spironolactone) plus EMPA 10 mg daily, and Group M received standard HF treatment plus metformin 500 mg daily. After three months of treatment, Group E had a significantly higher EF than Group M compared to initial measurements (a change of 9.2% versus 6.1%, respectively). We found similar results in the left ventricular end-systolic dimension (LVESD), with mean reductions of 0.72 mm for Group E and 0.23 mm for Group M. Regarding cardiac indicators, the level of NT-proBNP was considerably decreased in both groups. However, the reduction was significantly greater in group E than in group M compared to the initial level (mean reduction: 719.9 vs. 973.6, respectively). When combined with quadruple anti-heart failure therapy, metformin enhanced several echocardiographic parameters, showing effects similar to those of EMPA when used in the same treatment regimen. However, the benefits of EMPA were more pronounced, particularly regarding improvements in EF and LVESD.
Assuntos
Compostos Benzidrílicos, Glucosídeos, Insuficiência Cardíaca, Metformina, Volume Sistólico, Humanos, Insuficiência Cardíaca/tratamento farmacológico, Insuficiência Cardíaca/fisiopatologia, Compostos Benzidrílicos/uso terapêutico, Compostos Benzidrílicos/farmacologia, Glucosídeos/uso terapêutico, Glucosídeos/farmacologia, Metformina/uso terapêutico, Metformina/farmacologia, Volume Sistólico/efeitos dos fármacos, Masculino, Feminino, Estudos de Casos e Controles, Pessoa de Meia-Idade, Idoso, Peptídeo Natriurético Encefálico/sangue, Fragmentos de Peptídeos/sangue, Ecocardiografia, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Inibidores do Transportador 2 de Sódio-Glicose/farmacologiaRESUMO
Polycystic ovary syndrome is the most common cause of oligo-ovulation and anovulation among women of reproductive age, contributing to infertility. This study aimed to compare the effects of green tea tablets and metformin on ovulation, menstrual cycle regularity, and antioxidant biomarkers in women with polycystic ovary syndrome (PCOS). In this clinical trial study, 94 women with PCOS were randomly assigned to three groups: green tea (n = 33), metformin (n = 29), and control (n = 32). Menstrual status and oxidative stress parameters, including total antioxidant capacity, thiol, and lipid peroxidation, were compared before and 3 months after the intervention among all three groups. Data analysis was conducted using SPSS software version 22 and employing the analysis of variance and paired t-tests. Following the intervention, the mean menstrual cycle duration in the green tea, metformin, and control groups was 32.22 ± 12.78, 48.72 ± 37.06, and 48.53 ± 31.04 days, respectively (P = 0.040). There was no statistically significant difference between the three groups in terms of biochemical, hormonal, and antioxidant indices before and after the intervention (P > 0.05). The intake of green tea tablets was associated with better outcomes in regulating the menstrual cycle in women with PCOS.
Assuntos
Ciclo Menstrual, Metformina, Ovulação, Síndrome do Ovário Policístico, Comprimidos, Chá, Humanos, Síndrome do Ovário Policístico/tratamento farmacológico, Feminino, Metformina/uso terapêutico, Metformina/farmacologia, Ciclo Menstrual/efeitos dos fármacos, Adulto, Ovulação/efeitos dos fármacos, Adulto Jovem, Antioxidantes/uso terapêutico, Estresse Oxidativo/efeitos dos fármacosRESUMO
The coronavirus disease (COVID-19) pandemic has continued for 5 years. Sporadic cases continue to occur in different locations. Type 2 diabetes mellitus (T2DM) is associated with a high risk of a poor prognosis in patients with COVID-19. Successful control of blood glucose levels can effectively decrease the risks of severe infections and mortality. However, the effects of different treatments were reported differently and even adversely. This retrospective study included 4,922 patients who have been diagnosed as COVID-19 and T2DM from 138 Hubei hospitals. The clinical characteristics and outcomes were compared and calculated their risk for death using multivariate Cox regression and Kaplan-Meier curves. After adjustment of age, sex, comorbidities, and in-hospital medications, metformin and alpha-glucosidase inhibitor (AGI) use performed lower all-cause mortality (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI]: 0.24-0.71; p = 0.001 for metformin; 0.53, 0.35-0.80, p = 0.002 for AGIs), while insulin use was associated with increased all-cause mortality (adjusted HR, 2.07, 95% CI, 1.61-2.67, p < 0.001). After propensity score-matched (PSM) analysis, adjusted HRs for insulin, metformin, and AGIs associated with all-cause mortality were 1.32 (95% CI, 1.03-1.81; p = 0.012), 0.48 (95% CI, 0.23-0.83, p = 0.014), and 0.59 (95% CI, 0.35-0.98, p = 0.05). Therefore, metformin and AGIs might be more suitable for patients with COVID-19 and T2DM while insulin might be used with caution.
Assuntos
COVID-19, Diabetes Mellitus Tipo 2, Hipoglicemiantes, Metformina, Humanos, Diabetes Mellitus Tipo 2/mortalidade, Diabetes Mellitus Tipo 2/tratamento farmacológico, COVID-19/mortalidade, Masculino, Feminino, Estudos Retrospectivos, Pessoa de Meia-Idade, China/epidemiologia, Idoso, Metformina/uso terapêutico, Hipoglicemiantes/uso terapêutico, SARS-CoV-2, Insulina/uso terapêutico, Inibidores de Glicosídeo Hidrolases/uso terapêutico, AdultoRESUMO
OBJECTIVE: This study aims to examine the short-term effects of oral metformin (MET) on serum anti-müllerian hormone (AMH) levels and to verify its impact on AMH concentrations in women with polycystic ovary syndrome (PCOS). METHODS: The literature search, extending from January 2000 to April 2023, was conducted using databases such as PubMed, Embase, and the Cochrane Central, resulting in the inclusion of 20 studies. These selected studies, evaluated for quality using the Newcastle-Ottawa Scale, investigated changes in AMH levels before and after treatment, with durations ranging from less than three months to over six months. The reported outcomes were quantified as standardized mean differences (SMD) with 95% confidence intervals (CI). This comprehensive systematic review and meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42023420705. The statistical analyses were performed using Review Manager 5.4.1. RESULTS: â The study incorporated 20 articles, consisting of 12 prospective studies, 7 randomized controlled trials (RCT), and 1 cross-sectional study. â¡ Serum AMH levels in patients with PCOS diminish subsequent to the oral administration of MET. ⢠Across the spectrum of studies analyzed, a pronounced degree of heterogeneity is evident, potentially ascribed to differential parameters including body mass index (BMI), daily pharmacological dosages, the temporal extent of treatment regimens, criteria of PCOS, and detection Methods. ⣠The impact of MET on AMH levels exhibits a dose-responsive trend, with escalating doses of MET being associated with progressively greater declines in AMH concentrations in the patient population. ⤠For women with PCOS receiving MET therapy, a minimum treatment duration of three months may be necessary to observe a reduction in serum AMH levels. CONCLUSIONS: The results of this meta-analysis indicate that MET treatment exerts a suppressive effect on serum AMH levels in women with PCOS. It appears that a treatment duration of at least three months is required to achieve a significant decrease in AMH concentrations. Furthermore, the influence of MET on AMH is dose-dependent, with higher doses correlating with more pronounced reductions in AMH levels among the patients studied.
Assuntos
Metformina, Hormônios Peptídicos, Síndrome do Ovário Policístico, Feminino, Humanos, Hormônio Antimülleriano, Síndrome do Ovário Policístico/complicações, Síndrome do Ovário Policístico/tratamento farmacológico, Administração Oral, Índice de Massa Corporal, Metformina/uso terapêuticoRESUMO
OBJECTIVE: Non-small-cell lung cancer (NSCLC) is a deadly form of cancer that exhibits extensive intercellular communication which contributed to chemoradiotherapy resistance. Recent evidence suggests that arrange of key proteins are involved in lung cancer progression, including gap junction proteins (GJPs). METHODS AND RESULTS: In this study, we examined the expression patterns of GJPs in NSCLC, uncovering that both gap junction protein, beta 2 (GJB2) and gap junction protein, beta 2 (GJB3) are increased in LUAD and LUSC. We observed a correlation between the upregulation of GJB2, GJB3 in clinical samples and a worse prognosis in patients with NSCLC. By examining the mechanics, we additionally discovered that nuclear factor erythroid-2-related factor 1 (NFE2L1) had the capability to enhance the expression of connexin26 and connexin 31 in the NSCLC cell line A549. In addition, the use of metformin was discovered to cause significant downregulation of gap junction protein, betas (GJBs) by limiting the presence of NFE2L1 in the cytoplasm. CONCLUSION: This emphasizes the potential of targeting GJBs as a viable treatment approach for NSCLC patients receiving metformin.
Assuntos
Carcinoma Pulmonar de Células não Pequenas, Neoplasias Pulmonares, Metformina, Humanos, Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico, Carcinoma Pulmonar de Células não Pequenas/genética, Carcinoma Pulmonar de Células não Pequenas/metabolismo, Neoplasias Pulmonares/tratamento farmacológico, Neoplasias Pulmonares/genética, Neoplasias Pulmonares/metabolismo, Metformina/farmacologia, Metformina/uso terapêutico, Conexinas/genética, Conexinas/metabolismo, Conexinas/uso terapêutico, Junções Comunicantes/metabolismo, Fator 1 Relacionado a NF-E2/metabolismoRESUMO
Cancer continues to pose a significant global health challenge, as evidenced by the increasing incidence rates and high mortality rates, despite the advancements made in chemotherapy. The emergence of chemoresistance further complicates the effectiveness of treatment. However, there is growing interest in the potential of metformin, a commonly prescribed drug for type 2 diabetes mellitus (T2DM), as an adjuvant chemotherapy agent in cancer treatment. Although the precise mechanism of action of metformin in cancer therapy is not fully understood, it has been found to have pleiotropic effects, including the modulation of metabolic pathways, reduction in inflammation, and the regulation of cellular proliferation. This comprehensive review examines the anticancer properties of metformin, drawing insights from various studies conducted in vitro and in vivo, as well as from clinical trials and observational research. This review discusses the mechanisms of action involving both insulin-dependent and independent pathways, shedding light on the potential of metformin as a therapeutic agent for different types of cancer. Despite promising findings, there are challenges that need to be addressed, such as conflicting outcomes in clinical trials, considerations regarding dosing, and the development of resistance. These challenges highlight the importance of further research to fully harness the therapeutic potential of metformin in cancer treatment. The aims of this review are to provide a contemporary understanding of the role of metformin in cancer therapy and identify areas for future exploration in the pursuit of effective anticancer strategies.
Assuntos
Diabetes Mellitus Tipo 2, Metformina, Neoplasias, Humanos, Metformina/farmacologia, Metformina/uso terapêutico, Diabetes Mellitus Tipo 2/tratamento farmacológico, Proliferação de Células, Quimioterapia Adjuvante, Hiperplasia, Neoplasias/tratamento farmacológicoRESUMO
FUNDING: No external funding.
Assuntos
Diabetes Mellitus, Neoplasias Hematológicas, Metformina, Humanos, Metformina/uso terapêuticoRESUMO
The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.
Assuntos
Diabetes Mellitus Tipo 2, Metformina, Humanos, Metformina/uso terapêutico, Receptores Ativados por Proliferador de Peroxissomo, Hipoglicemiantes/uso terapêutico, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/induzido quimicamente, Quimioterapia CombinadaRESUMO
BACKGROUND: Combining cytotoxic chemotherapy or novel anticancer drugs with T-cell modulators holds great promise in treating advanced cancers. However, the response varies depending on the tumor immune microenvironment (TIME). Therefore, there is a clear need for pharmacologically tractable models of the TIME to dissect its influence on mono- and combination treatment response at the individual level. METHODS: Here we establish a patient-derived explant culture (PDEC) model of breast cancer, which retains the immune contexture of the primary tumor, recapitulating cytokine profiles and CD8+T cell cytotoxic activity. RESULTS: We explored the immunomodulatory action of a synthetic lethal BCL2 inhibitor venetoclax+metformin drug combination ex vivo, discovering metformin cannot overcome the lymphocyte-depleting action of venetoclax. Instead, metformin promotes dendritic cell maturation through inhibition of mitochondrial complex I, increasing their capacity to co-stimulate CD4+T cells and thus facilitating antitumor immunity. CONCLUSIONS: Our results establish PDECs as a feasible model to identify immunomodulatory functions of anticancer drugs in the context of patient-specific TIME.
