Metformin as an adjunct therapy for the treatment of moderate to severe acne vulgaris: A randomized open‐labeled study

Insulin, insulin‐like growth factor‐1 (IGF‐1) and essential amino acids activate the mechanistic target of rapamycin complex 1 (mTORC1), the main nutrient‐sensitive kinase. Metformin, through inhibition of mTORC1 may improve acne. A 12‐week, randomized, open‐labeled study evaluated the efficacy and safety of metformin as an adjunct for moderate to severe facial acne. In total, 84 patients received either oral tetracycline 250 mg bd and topical benzoyl peroxide 2.5% with or without metformin 850 mg daily. Evaluations constituted lesion counts, the Cardiff Acne Disability Index (CADI), metabolic parameters and treatment success rate (Investigators Global Assessment score of 0 or 1 or improvement of two grades). Treatment success rates were higher in the metformin group (66.7% vs. 43.2%; p = .04). The mean percentage reduction from baseline in total lesion counts at Week 12 was greater in the metformin group (71.4% vs. 65.3%; p = .278). The CADI scores showed a greater mean reduction in the metformin group (4.82 vs. 4.22; p = .451). Metformin was equally efficacious in improving acne in lean and overweight subjects. Gastrointestinal symptoms were noted in 31.7% of subjects on metformin. This study presents favorable data for metformin as an adjunct for acne treatment. Further randomized placebo‐controlled studies are required.     

Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation

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西格列汀联合二甲双胍治疗肥胖型2型糖尿病的疗效及对体脂含量情况分析

目的研究肥胖型2型糖尿病患者联合采用西格列汀、二甲双胍治疗的临床效果。方法选择2018年10月—2020年4月该院100例肥胖型2型糖尿病患者为研究对象,采用随机数表法分成常规组和治疗组,每组50例。常规组予二甲双胍治疗,治疗组予二甲双胍+西格列汀治疗。比较两组治疗效果、血糖指标、体脂含量、胰岛功能指标及不良反应。。结果两组治疗效果比较,差异有统计学意义(P<0.05)。治疗后常规组血糖指标高于治疗组,差异有统计学意义(t=8.183、4.828、18.158,P<0.05)。治疗后常规组体脂含量高于治疗组,差异有统计学意义(t=5.993、7.657、4.420,P<0.05)。治疗后两组胰岛功能比较,差异有统计学意义(t=5.898、5.283、16.033,P<0.05)。常规组不良反应总发生率低于治疗组,但差异无统计学意义(χ²=0.136,P=0.712)。结论西格列汀、二甲双胍联合治疗肥胖型2型糖尿病效果确切。     

Comparison of myo-inositol and metformin on glycemic control,lipid profiles,and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome: a randomized controlled clinical trial

Abstract

This investigation was conducted to evaluate comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome (PCOS). This randomized controlled trial was conducted on 53 women with PCOS, aged 18–40 years old. Subjects were randomly allocated into two groups to take either myo-inositol (n?=?26) or metformin (n?=?27) for 12 weeks. Myo-inositol supplementation, compared with metformin, significantly reduced fasting plasma glucose (FPG) (β ?5.12?mg/dL; 95% CI, ?8.09, ?2.16; p=.001), serum insulin levels (β ?1.49 µIU/mL; 95% CI, ?2.28, ?0.70; p<.001), homeostasis model of assessment-insulin resistance (β ?0.36; 95% CI, ?0.55, ?0.17; p<.001), serum triglycerides (β 12.42?mg/dL; 95% CI, ?20.47, ?4.37; p=.003) and VLDL-cholesterol levels (β ?2.48?mg/dL; 95% CI, ?4.09, ?0.87; p=.003), and significantly increased the quantitative insulin sensitivity check index (β 0.006; 95% CI, 0.002, 0.01; p=.006) compared with metformin. Moreover, myo-inositol supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (p=.002) compared with metformin. Overall, taking myo-inositol, compared with metformin, for 12 weeks by women with PCOS had beneficial effects on glycemic control, triglycerides and VLDL-cholesterol levels, and gene expression of PPAR-γ.     

PCOS: diagnosis and management of related infertility

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. It is characterised by a combination of hyperandrogenism (either clinical or biochemical), chronic oligo/anovulation, and polycystic ovaries. It is frequently associated with insulin resistance and obesity. PCOS receives considerable attention because of its high prevalence and possible reproductive, metabolic, and cardiovascular consequences. It is the most common cause of anovulatory infertility. Ovulation induction with an aromatase inhibitor or anti-oestrogen is the first-line medical treatment. The aim of ovulation induction is monofollicular growth to avoid multiple pregnancy. The second-line treatments include gonadotrophins and laparoscopic ovarian drilling. The role and benefit of metformin in ovulation induction is uncertain. Woman with PCOS undergoing IVF are at significant risk of ovarian hyperstimulation syndrome. Women with PCOS are also at an increased risk of developing gestational diabetes, pregnancy-induced hypertension, and pre-eclampsia.     

Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects

PurposeFixed-combination drug products (FCDPs) for patients with type 2 diabetes mellitus (T2DM) may show efficacy comparable to their individual components (ICs) while improving adherence to treatment. This study evaluated the bioequivalence and safety of 2 dapagliflozin/saxagliptin/metformin extended-release (XR) FCDPs relative to their ICs: saxagliptin and dapagliflozin/metformin XR.MethodsThis randomized, open-label, single-dose, single-center crossover study was conducted in 84 healthy subjects aged 18–55 years. The primary objective was to evaluate the fed-state bioequivalence of a dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP and a dapagliflozin 10-mg/saxagliptin 5-mg/metformin 1000-mg XR FCDP relative to the ICs. Secondary objectives included the evaluation of the effect of food on the pharmacokinetic (PK) parameters of saxagliptin, dapagliflozin, and metformin in both FCDPs and characterization of the PK parameters of the active metabolite of saxagliptin, 5-hydroxy saxagliptin, in healthy subjects. PK parameters (AUC_0–∞, AUC_0–t, and C_max) were used to assess the bioequivalence of the 2 FCDPs with their ICs. The C_max and AUC_0–t of the study drugs were compared between female and male subjects to assess sex differences in exposure. Safety and tolerability of both FCDPs and ICs were also assessed with adverse events, vital signs (systolic and diastolic blood pressures and pulse rate), 12-lead ECG, physical examinations, and laboratory assessments.FindingsBoth dapagliflozin/saxagliptin/metformin XR FCDPs were bioequivalent to their ICs. For the dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP, the 90% CI for the geometric mean ratio of dapagliflozin C_max was slightly above the 80%–125% bioequivalence limit, which is unlikely to be clinically relevant. Food delayed the absorption of the study drugs in both FCDPs, which is unlikely to have a clinically relevant impact on efficacy. In both cohorts, exposure was higher in female subjects compared with male subjects, potentially due to the lower body weight of the female subjects. The safety profile and tolerability of the FCDPs were similar to those of their ICs, and no deaths or serious adverse events were reported.ImplicationsThese data support the use of the dapagliflozin/saxagliptin/metformin XR FCDP in patients with T2DM. ClinicalTrials.gov identifier: NCT03169959.     

Endogenous testosterone determines metformin action on prolactin levels in hyperprolactinaemic men: A pilot study

Metformin was found to reduce elevated prolactin levels in women but not in men. The current study was aimed at investigating whether endogenous testosterone determines the impact of metformin on lactotroph function in men. This prospective case‐control study included 28 men with recently diagnosed type 2 diabetes mellitus and mild or moderate hyperprolactinaemia, 14 of whom had low testosterone levels, while in the remaining 14 ones' testosterone levels were within the reference range. All participants received metformin (2.55‐3 g daily) for the following 4 months. Circulating levels of glucose, insulin, prolactin, testosterone, oestradiol, gonadotropins, sex hormone‐binding globulin adrenocorticotropic hormone, insulin‐like growth factor‐1, thyrotropin and free thyroid hormones were measured at the beginning and at the end of the study. Although metformin reduced plasma glucose levels and improved insulin sensitivity in both groups, this effect was stronger in participants with low testosterone levels. Only in patients with abnormally low testosterone levels, the drug decreased prolactin levels. This effect, which was accompanied by an increase in luteinizing hormone levels, was inversely correlated with baseline testosterone and calculated free testosterone levels, and positively with treatment‐induced improvement in insulin sensitivity. In both treatment groups, metformin produced a neutral effect on plasma levels of the remaining hormones. The obtained results suggest that endogenous testosterone may attenuate the impact of metformin on lactotropic cells.     

炔雌醇环丙孕酮片用于PCOS不孕治疗中的效果

目的 分析炔雌醇环丙孕酮片(达英-35)、二甲双胍联合克罗米芬序贯用于治疗多囊卵巢综合征不孕的临床效果.方法 选取在医院接受治疗的多囊卵巢综合征不孕患者88例,选取时间为2017年10月—2018年12月,随机将所有患者分为2组,即对照组(44例)、观察组(44例),对照组患者行炔雌醇环丙孕酮片、克罗米芬序贯治疗,观察组患者行达英-35、二甲双胍联合克罗米芬序贯治疗.结果 经过治疗后,观察组患者的妊娠率为86.36%,明显高于对照组患者的妊娠率,数据差异显著,P<0.05;治疗后,两组患者的LH、FSH、T、E2等激素水平与治疗前对比,差异显著,P<0.05;治疗后,观察组患者的LH、FSH、T、E2等激素水平与对照组对比,数据差异较明显,P<0.05.结论 多囊卵巢综合征不孕患者接受炔雌醇环丙孕酮片、二甲双胍联合克罗米芬序贯治疗,可以改善患者的激素水平,提高患者的妊娠几率.