Oral Metformin Research Articles

Antihyperglycemic Effects of Annona cherimola Miller and the Flavonoid Rutin in Combination with Oral Antidiabetic Drugs on Streptozocin-Induced Diabetic Mice.

Ethanolic extract obtained from Annona cherimola Miller (EEAc) and the flavonoid rutin (Rut) were evaluated in this study to determine their antihyperglycemic content, % HbA1c reduction, and antihyperlipidemic activities. Both treatments were evaluated separately and in combination with the oral antidiabetic drugs (OADs) acarbose (Aca), metformin (Met), glibenclamide (Gli), and canagliflozin (Cana) in acute and subchronic assays. The evaluation of the acute assay showed that EEAc and Rut administered separately significantly reduce hyperglycemia in a manner similar to OADs and help to reduce % HbA1c and hyperlipidemia in the subchronic assay. The combination of EEAc + Met showed the best activity by reducing the hyperglycemia content, % HbA1c, Chol, HDL-c, and LDL-c. Rutin in combination with OADs used in all treatments significantly reduced the hyperglycemia content that is reflected in the reduction in % HbA1c. In relation to the lipid profiles, all combinate treatments helped to avoid an increase in the measured parameters. The results show the importance of evaluating the activity of herbal remedies in combination with drugs to determine their activities and possible side effects. Moreover, the combination of rutin with antidiabetic drugs presented considerable activity, and this is the first step for the development of novel DM treatments.

Cost-effectiveness of Empagliflozin, in Addition to Metformin, in Patients with Type 2 Diabetes in Italy

BACKGROUND: Cardiovascular diseases represent the main cause of mortality and morbidity in type 2 diabetes mellitus (T2DM) patients. Empagliflozin is used as a treatment for T2DM because of its association with reduced risk of hospitalization for heart failure (hHF). Recently oral semaglutide, in association with metformin, has shown better results. This study analyzes the cost-effectiveness of empagliflozin versus oral semaglutide, in addition to metformin, in patients with T2DM who are inadequately controlled on metformin alone in Italy.METHODS: This analysis was conducted from the Italian National Health Service (SSN) perspective using the IQVIA Core Diabetes Model. For the base case analysis, a 50-year time horizon was chosen to capture the complications, their associated costs, and the final impact on life-years (LYs) and quality-adjusted life-years (QALYs) gained. Cohort baseline characteristics and efficacy data, were mainly sourced from the PIONEER 2 study. Health-state utilities and event disutilities were based on published sources. Drug acquisition and administration costs and patient management inputs were sourced from Italian-specific data. A sensitivity analysis and a range of scenario analyses were carried out.RESULTS: In the base case analysis treatment cost of empagliflozin plus metformin were significantly lower compared to oral semaglutide plus metformin both including and excluding the effect of empagliflozin on hHF (€-13.371/€-13.580; LYs -0.004/0.109 and QALYs -0.037/0.038). The sensitivity analysis confirmed the robustness of the model with empagliflozin plus metformin that was dominant in 63% and in 42% of simulations considering and non-considering the treatment effect on hHF, respectively.CONCLUSIONS: Empagliflozin 25 mg plus metformin is a cost-effective option versus oral semaglutide 14 mg plus metformin for patients with T2DM uncontrolled on metformin alone in Italy

Metformin combined with endoscopic therapy in patients with familial polyposis associated with carcinoma: A case report.

Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease, with a very high cancer rate. At present, endoscopic resection of polyps ≥ 1 cm is often chosen for patients with non-cancerous polyps who are unwilling to undergo surgery, and regular review is conducted. Once the polyps are pathologically confirmed to be cancerous, surgical resection of the diseased large intestine is generally recommended, but surgery often leads to a series of complications. So what do you do with cancer patients who don't want surgery? A 19-year-old woman presented with intermittent hematochezia with abdominal pain. A colonoscopy revealed hundreds of intestinal polyps. The patient had a family history of FAP, and there were hundreds of polyps in the intestine. The pathology was adenomatous, and some polyps became cancerous, which met the diagnostic criteria of FAP. Endoscopic examination was arranged for the patient, the resection of intestinal polyps ≥ 1 cm was given priority, and other polyps were removed as far as possible. After that, metformin 500 mg orally was given twice a day, and endoscopic follow-up was conducted every 6 months. During each endoscopic follow-up, intestinal polyps ≥ 1 cm were preferred to be removed, and other polyps were removed as far as possible. The patient's abdominal pain and blood in the stool disappeared after endoscopic treatment. Cancerous polyps were found at the second and third follow-up visits, but the patient always refused surgical treatment. After 4 years of follow-up, polyp load was significantly reduced, abdominal pain and bloody stool symptoms did not appear again, and imaging examination showed no tumor recurrence and metastasis. Endoscopic polyp resection is an important method to treat the clinical symptoms of FAP. Metformin combined with endoscopic therapy is a good alternative for patients with familial polyposis who do not want surgery. When the polyp is cancerous and the polyp is radically resected by the endoscope, if the patient refuses additional surgery, oral metformin combined with endoscopic follow-up can be considered.

Association Between Oral Metformin Use and the Development of Age-Related Macular Degeneration in Diabetic Patients: A Systematic Review and Meta-Analysis.

Metformin is a biguanide derivative that is commonly used for the treatment of diabetes mellitus (DM). It demonstrates antioxidative, anti-inflammatory, and antiangiogenic activity within the ocular tissue and thus may be implicated in the treatment of age-related macular degeneration (AMD). However, epidemiological studies have shown conflicting results. The Ovid MEDLINE/Embase, Cochrane Library, and Web of Science databases were systematically searched from inception through August 3, 2022. Studies reporting the association between metformin use and odds of AMD were enrolled. Adjusted odds ratios (ORs) of AMD were extracted and pooled with random-effects model meta-analysis. Subgroup analyses based on AMD subtypes, ethnicity, study design, sex, and confirmation of AMD diagnosis were conducted. A total of 9 observational studies with 1,446,284 participants were included in the analysis. The meta-analysis showed that metformin use was associated with a significant reduction in the odds of AMD (pooled ORs = 0.81, 95% confidence interval [CI] = 0.70-0.93). Subgroup analyses revealed that metformin use was not significantly associated with dry or wet AMD. Black (pooled ORs = 0.61, 95% CI = 0.58-0.64) and Hispanic populations (pooled ORs = 0.85, 95% CI = 0.81-0.89) demonstrated significantly lower odds of AMD. This systematic review and meta-analysis found that patients with DM with metformin usage were at lower odds of developing AMD. Future prospective clinical trials are needed to confirm this association.

Evidence for Involvement of GIP and GLP-1 Receptors and the Gut-Gonadal Axis in Regulating Female Reproductive Function in Mice.

Substantial evidence suggests crosstalk between reproductive and gut-axis but mechanisms linking metabolism and reproduction are still unclear. The present study evaluated the possible role of glucose-dependent-insulinotropic-polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1) in reproductive function by examining receptor distribution and the effects of global GIPR and GLP-1R deletion on estrous cycling and reproductive outcomes in mice. GIPR and GLP-1R gene expression were readily detected by PCR in female reproductive tissues including pituitary, ovaries and uterine horn. Protein expression was confirmed with histological visualisation of incretin receptors using GIPR-Cre and GLP1R-Cre mice in which the incretin receptor expressing cells were fluorescently tagged. Functional studies revealed that female GIPR-/- and GLP-1R-/- null mice exhibited significantly (p < 0.05 and p < 0.01) deranged estrous cycling compared to wild-type controls, indicative of reduced fertility. Furthermore, only 50% and 16% of female GIPR-/- and GLP-1R-/- mice, respectively produced litters with wild-type males across three breeding cycles. Consistent with a physiological role of incretin receptors in pregnancy outcome, litter size was significantly (p < 0.001-p < 0.05) decreased in GIPR-/- and GLP-1R-/- mice. Treatment with oral metformin (300 mg/kg body-weight), an agent used clinically for treatment of PCOS, for a further two breeding periods showed no amelioration of pregnancy outcome except that litter size in the GIPR-/- group was approximately 2 times greater in the second breeding cycle. These data highlight the significance of incretin receptors in modulation of female reproductive function which may provide future targets for pharmacological intervention in reproductive disorders.

Abstract 11469: Effects of Metformin and Donepezil on the Prevention of Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patient: A Randomized Controlled Trial

Introduction: Cardiotoxicity from doxorubicin (DOX) is the most concerning adverse event. Although data from preclinical studies showed that metformin and donepezil prevented myocardial injury and preserved mitochondrial function against DOX-induced cardiotoxicity, the beneficial effects of these drugs in clinical trial have not been established. Hypothesis: Oral administration with metformin or donepezil prior receiving DOX prevents DOX-induced cardiotoxicity in breast cancer patients. Methods: In this double-blind, placebo-controlled trial. We randomly assigned 111 female breast cancer patients to receive oral metformin 2000 mg (n=40), donepezil 10 mg (n=31), or placebo (n=40), once daily 1 day prior to DOX and continued during DOX treatment. Blood samples were obtained at baseline, after chemotherapy cycle 2 and 4. The primary outcome was the change of troponin-I (trop-I) from baseline. The secondary outcomes were the change in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline, and mitochondrial function in the peripheral blood mononuclear cells. Results: Baseline characteristics were similar between the groups, mean age was 51.93±10.45 years. The mean trop-I changed from baseline were 29.97±4.59 pg/ml in placebo group, 31.07±7.28 pg/ml in metformin group (p = 0.90 vs. placebo) and 30.97±5.07 pg/ml in donepezil group (p = 0.88 vs. placebo). The changes of NT-proBNP level and mitochondrial oxidative stress were comparable between placebo vs. metformin or donepezil groups. However, donepezil significantly decreased mitochondrial mass and mitochondrial maximal respiration after chemotherapy (Figure). Conclusion: In breast cancer patients undergoing chemotherapeutic treatment with DOX, metformin and donepezil did not prevent myocardial injury. Treatment with donepezil resulted in the decrease in mitochondrial mass and maximal respiration following chemotherapy that might caution its use in breast cancer.

RF28 | PSUN183 Intestinal microbiota composition in patients with type 2 diabetes and effects of 12 weeks of oral anti-diabetic treatment

Abstract Introduction The cause-effect relationships of dysbiosis and type 2 diabetes are complex and remain to be elucidated, very likely a two-way interaction. The aim of the study was to evaluate intestinal microbiota composition in patients with type 2 diabetes. Material and Methods This is a case-control study among patients with type 2 diabetes. Individuals were eligible if they were aged ≥18 years, were newly diagnosed with type 2 diabetes, had HbA1c levels ≥6.5 and ≤10.0%, and have been treated for oral antidiabetic agents for 3 months. The primary endpoint was the change from baseline in intestinal microbiota compositon after 12 weeks of treatment and comparison with healthy controls. Secondary endpoints were; change from baseline in intestinal microbiota composition after 12 weeks of oral antidiabetic monotherapy and comparison with healthy controls. A minimum of 5 mL fresh stool sample was collected at Day O of the study and 12 weeks later in a 15 mL Falcon tube and rapidly transferred to −80 °C to be stored in an upright position until DNA extraction. The V3 and V4 regions of the 16S rRNA gene were amplified following the 16S Metagenomic Sequencing Library Preparation. RESULTS: During the study period, 44 eligible patients were planned to enroll the study. Detailed analysis has been performed in 24 patients with type 2 diabetes (receiving oral antidiabetic treatment, metformin or linagliptin) and 10 age-matched healthy controls. The Chao-1 and Shannon Index were lower in the type 2 diabetes group before and after treatment groups (p&amp;lt;0.01 for both). PCoA plots were constructed to demonstrate separation of groups of samples for unweighted UniFrac distance, weighted UniFrac distance, and Bray–Curtis dissimilarity distance and no statistically significant differences between or within the type 2 diabetes and healthy control groups. At the first visit (before treatment), at phylum level, Bacteroidetes abundance have been observed in diabetic group, while Actinobacteria and Firmicutes in healthy controls. At genera level, we observed Gemmiger and Collinsella predominance in diabetes group; however, Faecalibacterium, Bacteroides and Alistipes in healthy controls. After 12 weeks of treatment, at genera level, Lactobacillus, Rothia and Collinsella increased in type 2 diabetes group however, microbiota composition was still different comparing the healthy controls. In patients receiving 12 weeks of metformin, Prevotella and Lactobacillus increased at genera level while Dialister and Ruminocococcus decreased. DISCUSSION: We report that there is a substantial change in the composition of the gut microbiota in patients with type 2 diabetes. We observed the beneficial effects as relative abundance of short chain fatty acid producing bacteria increased (eg, Prevotella, Lactobacillus) in metformin group. The interaction of the anti-diabetic drugs with gut microbiota have been less studied, further studies will highlight the clinical effect of these alteration in intestinal microbiota composition in diabetes. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:37 p.m. - 12:42 p.m.

PMON246 Prevalence of Hypertension and Metabolic Syndrome in Women with PCOS from France and Brazil

Abstract Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting women of reproductive age and has been associated with metabolic and reproductive abnormalities. Evidence from different geographic regions indicates that the metabolic features of PCOS may be influenced by ethnicity, lifestyle and sociocultural backgrounds. Also, metabolic disturbances seem to be found in higher frequency in referral than in unselected populations and from a clinical practice point of view, data from referral samples may be relevant for adjusting effective primary and secondary prevention strategies. Therefore, the aim of this study was to determine the prevalence of systemic arterial hypertension and metabolic syndrome (MBS) in women with PCOS from France and Brazil. We retrospectively assessed 314 French (FR) women and 236 Brazilian (BR) women with PCOS, according to the Rotterdam criteria, aging between 18 and 42 years and not using combined oral contraceptives or metformin. These women had been referred to the respective University Hospitals between 2014 to 2021 in France and 2014 to 2020 in Brazil. BR women had participated in previous studies conducted at our research center. Hypertension was defined according to the ACC/AHA 2017 and MBS according to the Joint Scientific Statement, 2009. Mean age was 26.0 (SD 5.9) years FR and 25.9 (SD 5.8) BR, p=0.87, and mean body mass index (BMI) was 27.1 (SD 6.8) FR and 31.3 (SD 7.5) BR P&amp;lt;0.001. The frequency of classical phenotype (A/B) was 83.7% in FR (n=262) and 77.1% in BR (n=182), p =0.071. Subsequent analyses were done including only women presenting the classical phenotype from each center. FR women with PCOS presented lower prevalence of overweight/obesity (53.7% FR vs. 84.6% BR, p&amp;lt;0.001), hypertension (32.6% FR vs. 71.6% BR, p&amp;lt;0.001) and MBS (12.5% FR vs. 38.5% BR, p&amp;lt; 0.001) than BR women with PCOS. Using logistic regression models for hypertension and MBS, it was found that both BMI and country contributed significantly for these prevalence results. In conclusion, women with PCOS living in France presented a less severe metabolic profile than those living in south Brazil. Differences in dietary pattern, lifestyle, socio-cultural features and ethnicity may have contributed to these results. Further studies are warranted to deeper characterize the influence of dietary composition and lifestyle on prevalence ratios of metabolic features in women living in France. Sources of Research Support: INCT-CNPq /FAPERGS Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Sex-specific effects of maternal metformin intervention during glucose-intolerant obese pregnancy on body composition and metabolic health in aged mouse offspring

Aims/hypothesisMetformin is increasingly used to treat gestational diabetes (GDM) and pregnancies complicated by pregestational type 2 diabetes or polycystic ovary syndrome but data regarding long-term offspring outcome are lacking in both human studies and animal models. Using a mouse model, this study investigated the effects of maternal metformin intervention during obese glucose-intolerant pregnancy on adiposity, hepatic steatosis and markers of metabolic health of male and female offspring up to the age of 12 months.MethodsC57BL/6J female mice were weaned onto either a control diet (Con) or, to induce pre-conception obesity, an obesogenic diet (Ob). The respective diets were maintained throughout pregnancy and lactation. These obese dams were then randomised to the untreated group or to receive 300 mg/kg oral metformin hydrochloride treatment (Ob-Met) daily during pregnancy. In male and female offspring, body weights and body composition were measured from 1 month until 12 months of age, when serum and tissues were collected for investigation of adipocyte cellularity (histology), adipose tissue inflammation (histology and quantitative RT-PCR), and hepatic steatosis and fibrosis (histochemistry and modified Folch assay).ResultsAt 12 months of age, male Ob and Ob-Met offspring showed increased adiposity, adipocyte hypertrophy, elevated expression of proinflammatory genes, hyperleptinaemia and hepatic lipid accumulation compared with Con offspring. Male Ob-Met offspring failed to show hyperplasia between 8 weeks and 12 months, indicative of restricted adipose tissue expansion, resulting in increased immune cell infiltration and ectopic lipid deposition. Female Ob offspring were relatively protected from these phenotypes but Ob-Met female offspring showed increased adiposity, adipose tissue inflammation, hepatic lipid accumulation, hyperleptinaemia and hyperinsulinaemia compared with Con female offspring.Conclusions/interpretationMaternal metformin treatment of obese dams increased offspring metabolic risk factors in a sex- and age-dependent manner. These observations highlight the importance of following up offspring of both sexes beyond early adulthood after interventions during pregnancy. Our findings illustrate the complexity of balancing short-term benefits to mother and child vs any potential long-term metabolic effects on the offspring when prescribing therapeutic agents that cross the placenta.Graphical abstract

Abstract P087: Metformin Treatment Decreases Blood Pressure But Does Not Ameliorate Hypertensive Cardio-Renal Damage In A Double Transgenic Rat Model

Introduction: Metformin (Met) is used as a first-line treatment in type II diabetes, reduces the cardiovascular (CV) risk in diabetes and may lead to decreased CV mortality independent of diabetes status. Met treatment has been shown to induce gut microbiome changes leading to enhanced production of protective short-chain fatty acids and potentially harmful metabolites (LPS). Our study aims to examine the effects of Met in a model of RAAS-mediated hypertension with cardio-renal damage. Methods: Four-week-old double transgenic rats (dTGR, transgenic for human renin and angiotensinogen) received oral Metformin (Met) or Vehicle (Veh) for 3 weeks. SD rats served as healthy controls. Flow cytometry (n=10 per group), echocardiography (n=14), radiotelemetric blood pressure (BP) measurements (n=5), clinical chemistry and gene expression analyses (n=14) were used to assess damage to kidney and heart. Results: Met treatment did not influence survival nor lead to lactate acidosis. Met treatment lowered BP significantly (systolic BP: Met: 218±5 mmHg, Veh: 237±3 mmHg). Interestingly, the decreased BP was accompanied by increased cardiac hypertrophy (heart weight to tibia length, SD: 34±1 g/m, Met: 40±1 g/m, Veh: 37±1 g/m). Echocardiographic systolic and diastolic function was deteriorated (EF: Met: 64±2 %, Veh: 68±4 %; E/A: Met: 0.75±0.1, Veh: 0.93±0.1). Plasma BNP and cardiac ß-to-α MHC ratio were higher in Met-treated dTGR. Intestines, spleens, kidneys and hearts of dTGR showed a strong pro-inflammatory phenotype with increased adaptive (e.g. cardiac T cells % of leucocytes: (SD: 10±0.003 %, Met: 15±0.01 %, Veh: 13±0.01 %) and innate (e.g. cardiac monocytes % of leucocytes: (SD: 2±0.001 %, Met: 3±0.004 %, Veh: 5±0.02 %) immune cell subsets in comparison to SD rats; with almost no differences between Met- and Veh-treated dTGR. Fecal metagenomic shotgun sequencing showed no large-scale taxonomic shifts between Veh- and Met-treated dTGR. Conclusion: dTGR display a pronounced pro-inflammatory immunophenotype across several organs. Met did not ameliorate hypertensive target organ damage in dTGR despite the BP lowering effect. These findings could help to understand the effects of Met on the microbiome, immunome and organ damage in the context of hypertension.

A novel cocrystal of metformin hydrochloride with citric acid: Systematic synthesis and computational simulation

Pharmaceutical cocrystals have matured into an effective technique for tuning the physicochemical and mechanical properties of drugs in solid form simultaneously. Herein, in order to provide a novel cocrystal form of oral medicine metformin hydrochloride (MH), citric acid (CA) was selected as an efficient ligand after screening a variety of inorganic and organic acids. Thus, based on the principle of crystal engineering, we report a novel cocrystal: metformin hydrochloride - citric acid (MHCA) after the systematic screening, which was experimentally proved to be constituted with 1:1 stoichiometry. Compared with pure MH, MHCA has been proved higher solubility in water, methanol, and ethanol from 283.15 to 313.15 K. Through single-crystal X-ray diffraction (SC-XRD), the particular molecular structure of MHCA has been determined as the orthorhombic system and Pbca space group. Besides, the binding model of MH-CA was built for investigating the binding energy and stability between two components at 278, 298, and 318 K, which were found to be essential for the prediction and analysis of cocrystals. The contribution of different intermolecular interactions and the strength of molecular packing in the cocrystal also have been investigated by Hirshfeld surface analysis. It was found that the cocrystal structure was mainly stabilized by intermolecular hydrogen bonds existing as N—H···O between components, which indicated that the diffusion-combination trend of molecules enhanced the regular array of cocrystal. The results revealed that the molecules of MH and CA formed supramolecular cocrystals mainly induced by hydrogen bonds after passive contacts, such as co-crystallization or grind.

The role of GLP-1 receptor agonists in managing type 2 diabetes.

Glucagon-like peptide-1 (GLP-1) receptor agonists improve glycemic control in patients with type 2 diabetes mellitus, have cardioprotective and renoprotective effects, and do not cause weight gain or significant hypoglycemia. In fact, they have been found to be effective for weight loss in patients with obesity with and without diabetes. They are now the preferred drugs to add to the regimen when oral metformin by itself is not enough to meet the patient's hemoglobin A1c goal.

Modulation of autophagy, apoptosis and oxidative stress: a clue for repurposing metformin in photoaging

Long-term sun exposure is the commonest cause of photoaging, where mutual interplay between autophagy, oxidative stress, and apoptosis is incriminated. In combating photoaging, pharmacological approaches targeted to modulate autophagy are currently gaining more ground. This study aimed to examine repurposing metformin use in such context with or without the antioxidant coenzyme Q10 (coQ10) in ultraviolet A (UVA) irradiation-induced skin damage. The study was conducted on 70 female CD1 mice that were randomly assigned into seven groups (10/group): normal control, vehicle-treated-UVA-exposed mice, three metformin UVA-exposed groups (Topical 1 and 10%, and oral 300 mg/kg), topical coQ10 (1%)-treated mice, and combined oral metformin with topical coQ10-treated UVA-exposed mice. After UVA-exposure for 10 weeks (3 times/week), macroscopic signs of photoaging were evaluated. Mice were then euthanized, and the skin was harvested for biochemical estimation of markers for oxidative stress, inflammation, matrix breakdown, and lysosomal function. Histopathological signs of photoaging were also evaluated with immunohistochemical detection of associated changes in autophagic and apoptotic markers. Metformin, mainly by topical application, improved clinical and histologic signs of photoaging. This was associated with suppression of the elevated oxidative stress, IL-6, matrix metalloproteinase 1, and caspase, with induction of cathepsin D and subsequent change in anti-LC3 and P62 staining in skin tissue. In addition to metformin antioxidant, anti-inflammatory, and antiapoptotic activities, its anti-photoaging effect is mainly attributed to enhancing autophagic flux by inducing cathepsin D. Its protective effect is boosted by coQ10, which supports their potential use in photoaging.

The glucose tolerance test in mice: Sex, drugs and protocol.

To establish the impact of sex, dosing route, fasting duration and acute habituation stress on glucose tolerance test (GTT) measurements used in the preclinical evaluation of potential glucose-modulating therapeutics. Adult male and female C57Bl/6J mice, implanted with HD-XG glucose telemetry devices, were fasted for 16 hours or 6hours following acute habituation stress due to whole cage change, cage change with retention of used bedding or no cage change prior to intraperitoneal (IP) GTTs. To evaluate protocol refinement and sex on the ability of the GTT to detect drug effects, we administered 250 mg/kg oral metformin or 10nmol/kg IP exendin-4 using optimized protocols. Female mice were less sensitive to human intervention when initiating fasting. Following a 6-hour fast, retention of bedding whilst changing the cage base promotes quicker stabilization of basal blood glucose in both sexes. Prolonged fasting for 16 hours resulted in an exaggerated GTT response but induced pronounced basal hypoglycaemia. Following GTT protocol optimization the effect of exendin-4 and metformin was equivalent in both sexes, with females showing a more modest but more reproducible GTT response. Variations in GTT protocol have profound effects on glucose homeostasis. Protocol refinement and/or the use of females still allows for detection of drug effects, providing evidence that more severe phenotypes are not an essential prerequisite when characterizing/validating new drugs.

The potential role of insulin-like growth factor 1 in acne vulgaris and its correlation with the clinical response before and after treatment with metformin.

Acne vulgaris (AV) is a complex and multifactorial inflammatory disease affecting the pilosebaceous follicles. Optimum treatment of AV is important to reduce the disease severity and recurrence. To evaluate the role of metformin in the treatment of acne vulgaris by reducing the level of insulin-like growth factor 1. Fifty patients with AV were included in the study. Their ages ranged from 16 to 30 years, and they had different grades of the disease. IGF-1 levels were measured in all patients before and after the treatment with metformin. After 4 months of therapy, there was a clinical improvement detected by an improvement in the global acne grading system (GAGS) score and also a significant decrease in IGF-level. IGF-1 may have an important role in the pathogenesis of acne; also we can presume that oral metformin is an effective and safe line in the treatment of AV.

Application of Gestational Blood Glucose Control During Perinatal Period in Parturients with Diabetes Mellitus: Meta-Analysis of Controlled Clinical Studies.

BackgroundGestational diabetes mellitus (GDM) is a common metabolic disorder. Hyperglycemia may cause gestational hypertension, increase the probability of infection, abnormal embryonic development, and increase the abortion rate. Oral hypoglycemic drugs may be another effective means of blood glucose control in addition to insulin injection. We included controlled clinical studies for meta-analysis to understand the effect of oral hypoglycemic drugs in gestational diabetes.MethodsThe databases were searched with the keywords “Glycemic control” & “gestational diabetes”: Embase (January, 2000–August, 2021), Pubmed (January, 2000–August, 2021), Web of Science (January, 2000–August, 2021), Ovid (January, 2000–August, 2021), and ClinicalTrials.org to obtain the randomized controlled trial (RCT) literatures related to the treatment of gestational diabetes with oral hypoglycemic drugs, after screening, the R language toolkit was used for the analysis.ResultsA total of 10 articles with a total of 1,938 patients were included, 7 studies used metformin as an hypoglycemic agent. Meta-analysis showed that oral metformin had no significant difference in fasting blood glucose levels after the intervention compared with insulin injection [MD = −0.35, 95%CI(−0.70,1.40), Z = 0.66, P = 0.51], with no significant difference in postprandial blood glucose levels after intervention [MD = −2.20, 95%CI(−5.94,1.55), Z = −1.15, P = 0.25], and no statistical difference in glycosylated hemoglobin [MD = 0.10, 95%CI(−0.17,−0.04), Z = −0.94, P = 0.31]. Metformin was more conducive to reducing maternal weight during pregnancy than insulin [MD = −1.55, 95%CI(−2.77,−0.34), Z = −2.5, P = 0.0123], metformin reduced the abortion rate compared with insulin [RR = 0.81, 95%CI(0.63,1.05), Z = −2.61, P = 0.015], and reduced cesarean section rate [RR = 0.66, 95%CI(0.49,0.90), Z = −3.95, P = 0.0001].DiscussionThe application of oral hypoglycemic drug metformin in blood glucose control of gestational diabetes can play a hypoglycemic effect equivalent to insulin and can control the weight of pregnant women, reduce the rate of abortion and cesarean section, and improve pregnancy outcomes.

Ameliorating Effect on Glycolipid Metabolism of Spirulina Functional Formulation Combination from Traditional Chinese Medicine.

Insulin resistance is the major factor involved in the pathogenesis of type 2 diabetes. Although the oral drug metformin (MH) is widely used to reduce hyperglycemia, it is associated with adverse effects. Therefore, there is an urgent need to search for safe and natural foods that do not cause adverse effects as alternatives to commercial drugs. In this study, the active substances from Spirulina platensis, Grifola frondosa, Panax ginseng, and chromium-rich yeast were used to obtain Spirulina functional formulations (SFFs), and its therapeutic effects on mice with glycolipid metabolism disorder (GLD) were investigated. Results showed that SFFs not only improved glycolipid metabolism and reduced inflammation in mice with GLD but also showed good regenerative effects on the liver, jejunum, and cecum tissues. Moreover, SFFs could inhibit the growth of harmful microbes in the intestine and promote the proliferation of beneficial bacteria, thereby promoting the production of short-chain fatty acids and further regulating GLD. Additionally, SFFs significantly increased the expression of INS, INSR, IRS-1, PI3K, AKT-1, and GLUT-4 genes and significantly decreased that of GSK-3β in the INS/PI3K/GLUT-4 signaling pathway. Therefore, the findings of this study suggest that SFFs can be further developed as a new class of therapeutic agents against GLD.

Metformin Protects Cardiovascular Health in People With Diabetes.

BackgroundMetformin is the most commonly used drug for patients with diabetes, but there is still some controversy about whether it has a protective effect on cardiovascular health. We therefore used the National Health and Nutritional Examination Survey (NHANES) database to analyze the impact of metformin use on cardiovascular health in patients with diabetes.MethodsWe extracted the demographic data and laboratory test results of all people with diabetes in the NHANES database from January 2017 to March 2020. The outcomes were seven indicators of cardiovascular health from the American Heart Association, each was scored as 0, 1, and 2 to represent poor, moderate, and ideal health statuses, respectively. The scores for the indicators (excluding diet and glycemic status) were summed, and the sum score was then considered to indicate unhealthy (0–5) or healthy (>5). Multivariate logistic regression analysis was used, and subgroup analyses were performed by age, alcohol consumption, education, and marital status.ResultsThis study included 1,356 patients with diabetes, among which 606 were taking metformin. After adjusting for all included variables, oral metformin in patients with diabetes had a protective effect on the cardiovascular health of patients (OR = 0.724, 95% CI = 0.573–0.913, P = 0.007). Subgroup analysis indicated that metformin protects the cardiovascular health of people with diabetes more clearly in those who are young (OR = 0.655, 95% CI = 0.481–0.892, P = 0.007), married (OR = 0.633, 95% CI = 0.463–0.863, P = 0.003), and drink alcohol (OR = 0.742, 95% CI = 0.581–0.946, P = 0.016).ConclusionThis study found that metformin has a protective effect on the cardiovascular health of patients with diabetes. The study findings support the general applicability of metformin.

MET-PREVENT: metformin to improve physical performance in older people with sarcopenia and physical prefrailty/frailty – protocol for a double-blind, randomised controlled proof-of-concept trial

IntroductionSkeletal muscle dysfunction is central to both sarcopenia and physical frailty, which are associated with a wide range of adverse outcomes including falls and fractures, longer hospital stays, dependency and...

Real World Study of Effectiveness of Gemigliptin Add-On Therapy in Type 2 Diabetes Mellitus

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antidiabetic agents that increase endogenous levels of incretin hormones and lead to an increased insulin level and a reduced glucagon level in a glucose-dependent way. Gemigliptin, is a potent, selective, competitive, and long-acting DPP-4 inhibitor. The objective of our study was to evaluate the realworld efficacy and safety of gemigliptin. Materials and methods: A real-world prospective, observational, single-center study conducted in the Endocrinology Department, of a tertiary care hospital. 60 patients were included with 22 (36.7%) female patients. The treatment options consisted of uncontrolled metformin monotherapy, dual combination therapy, triple oral anti-hyperglycemic agents, metformin, and basal insulin combination. Weight, body mass index (BMI), fasting plasma glucose (FPG), 2 hours post postprandial glucose (PPG), HbA1c% were documented at baseline and followed up at 3 months. Results: The baseline HbA1c, FPG and PPG were 9.50 ± 2.24 %, 176.71 ± 67.076 mg/dL, 243.37 ± 93.97 mg/dl respectively. After 3 months of additional gemigliptin therapy, HbA1c, FPG, and PPG were significantly reduced to 8.24 ± 1.83%, 144.32 ± 50.664, 184.93 ± 69.66 respectively. Conclusions: In real world settings, gemigliptin, a new DPP-4 inhibitor was found to be effective, safe and well tolerated as add-on therapy in adult type 2 diabetes mellitus (T2DM) subjects.