Metformin Combination Therapy Research Articles

Effectiveness of dual combination therapy of acarbose plus metformin and acarbose plus myo-inositol in ameliorating the metabolic and endocrinologic complications of polycystic ovary syndrome – A randomized controlled trial

IntroductionPCOS, beyond being characterized by reproductive disturbances, is a complicated rapid expanding metabolic and endocrinologic disorder of the recent times. Nearly 70% PCOS women show resistance to insulin. AIM: The aim of the study is to determine and compare the effectiveness of acarbose plus metformin and acarbose plus myo-inositol combination therapy in alleviating the metabolic and endocrinologic complications of PCOS. Materials and methodsAn open labelled RCT was conducted on 168 PCOS women attending the gynaecology clinic at SRM MCH & RC, Chengalpattu and the trial was registered in CTRI (No. CTRI/2022/04/041877). Group A (n = 56) received metformin 500 mg/TID alone; group B (n = 54) received (acarbose 25 mg/TID for 4 weeks then 50 mg/TID for other 20 weeks) along with metformin 500 mg/TID and group C (n = 54) received (acarbose 25 mg/TID for 4 weeks then 50 mg/TID for other 20 weeks) along with myoinositol 1000 mg/BD. All parameters were measured at baseline and at the end of 6 months. ResultsSignificant reduction of LH, LH: FSH, TT, HOMA-IR was observed in all the groups. FSH increased only in metformin group. Increase in serum progesterone and reduction in FI, TGL, LDL were significant only in acarbose plus myo-inositol group. SHBG and HDL increased significantly only in acarbose plus metformin group. No changes in BMI, TC and VLDL were observed in any group. ConclusionTherefore, decrease in FI, HOMA-IR, TGL, LDL seen in acarbose plus myo-inositol group indirectly contributes to cardio-metabolic safety in PCOS. Similarly, a significant increase in SHBG levels with acarbose plus metformin group shows correction of the excess androgen and restoration of ovulation.

Expert opinion on the prescription practice of vildagliptin and its combinations in managing type 2 diabetes mellitus in Indian settings

Background: The aim of the study was to gather expert opinion regarding the use of vildagliptin and its combinations in T2DM in Indian settings. Methods: This cross-sectional study involved 24 questions and collected perspectives of experts across various clinical settings in India regarding the use of vildagliptin and its combinations for the management of type 2 diabetes mellitus (T2DM) in their clinical practice. Results: Among 195 participants, most clinicians (73%) advocated vildagliptin once-daily formulation for newly diagnosed young diabetics, elderly patients with long-standing diabetes, and those with uncontrolled diabetes as an add-on therapy. Around 92% favored vildagliptin for its weight-neutral nature, preservation of beta-cell function, minimal glycemic variation, and low risk of adverse effects. Most clinicians (66%) preferred initiating vildagliptin and metformin combination therapy in diabetic individuals aged 40 to 50 years, with 53% opting for it when HbA1c levels exceeded 8%. Approximately 83% favored this combination for young, elderly, and long-standing diabetic individuals. More than half (54%) of the clinicians preferred prescribing the fixed-dose combination (FDC) of vildagliptin and dapagliflozin to 11-25% of the patients. Conclusions: The survey underscored the effectiveness of vildagliptin and its combinations in managing T2DM. Clinicians widely endorsed vildagliptin once-daily formulation and vildagliptin and metformin therapy for diverse diabetic populations due to their efficacy and tolerability. They also advocated the use of vildagliptin and dapagliflozin therapy, especially in patients with specific comorbidities or higher HbA1c levels, citing its benefits in achieving better glycemic control and reducing disease progression.

Influencing factors of stroke in patients with type 2 diabetes: A systematic review and meta-analysis.

Stroke stands as a significant macrovascular complication among individuals with Type 2 diabetes mellitus (T2DM), often resulting in the primary cause of mortality and disability within this patient demographic. Presently, numerous studies have been conducted to investigate the underlying causes of stroke in individuals with T2DM, yet the findings exhibit inconsistencies. This paper aims to consolidate and summarize the available evidence concerning the influential factors contributing to stroke among patients diagnosed with T2DM. We conducted a comprehensive search across multiple databases, including Cochrane Library, PubMed, Web Of Science, Embase, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Weipu up to August 2023. Google Scholar was also searched to retrieve gray literature. We calculated odds ratios (OR) and 95% confidence intervals (CI) using Stata software. Our analysis encompassed 43 observational studies, exploring factors across sociodemographic, biochemical, complications, and hypoglycemic agent categories. The findings identified several risk factors for stroke in patients with T2DM: age, gender, T2DM duration, hypertension, body-mass index (BMI), smoking, Glycated hemoglobin (HbA1c), estimated Glomerular Filtration Rate (eGFR), albuminuria, Triglycerides (TG), Low density lipoprotein cholesterol (LDL-C), Coronary heart disease (CHD), Atrial fibrillation (AF), diabetic retinopathy (DR), Peripheral vascular disease (PVD), and carotid plaque. Conversely, exercise, High density lipoprotein cholesterol (HDL-C), metformin (MET), pioglitazone, and metformin combination therapy emerged as protective factors. This study underscores the multitude of influencing factors contributing to stroke in people with T2DM patients, among which the microvascular complications of T2DM play an most important role. Therefore, we emphasize the importance of screening for microvascular complications in patients with T2DM. However, due to limitations arising from the number of articles reviewed, there remain areas where clarity is lacking. Further research efforts are warranted to expand upon and reinforce our current findings.

Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Potential use of sodium glucose co-transporter 2 inhibitors during acute illness: a systematic review based on COVID-19.

SGLT-2i are increasingly recognized for their benefits in patients with cardiometabolic risk factors. Additionally, emerging evidence suggests potential applications in acute illnesses, including COVID-19. This systematic review aims to evaluate the effects of SGLT-2i in patients facing acute illness, particularly focusing on SARS-CoV-2 infection. Following PRISMA guidelines, a systematic search of PubMed, Scopus, medRxiv, Research Square, and Google Scholar identified 22 studies meeting inclusion criteria, including randomized controlled trials and observational studies. Data extraction and quality assessment were conducted independently. Out of the 22 studies included in the review, six reported reduced mortality in DM-2 patients taking SGLT-2i, while two found a decreased risk of hospitalization. Moreover, one study demonstrated a lower in-hospital mortality rate in DM-2 patients under combined therapy of metformin plus SGLT-2i. However, three studies showed a neutral effect on the risk of hospitalization. No increased risk of developing COVID-19 was associated with SGLT-2i use in DM-2 patients. Prior use of SGLT-2i was not associated with ICU admission and need for MV. The risk of acute kidney injury showed variability, with inconsistent evidence regarding diabetic ketoacidosis. Our systematic review reveals mixed findings on the efficacy of SGLT-2i use in COVID-19 patients with cardiometabolic risk factors. While some studies suggest potential benefits in reducing mortality and hospitalizations, others report inconclusive results. Further research is needed to clarify optimal usage and mitigate associated risks, emphasizing caution in clinical interpretation.

Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice

BackgroundRadiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), whether autologous or allogeneic, individually or in combination therapy, in mitigating RISF.MethodsUsing a female C57BL/6J mouse model subjected to hind limb irradiation as a representative RISF model, we evaluated metformin, ASCs, or their combination in two contexts: prophylactic (started on day 1 post-irradiation) and therapeutic (initiated on day 14 post-irradiation, coinciding with fibrosis symptoms). We measured limb movement, examined skin histology, and analyzed gene expression to assess treatment efficacy.ResultsProphylactic metformin and ASCs, whether autologous or allogeneic, effectively prevented late fibrosis, with metformin showing promising results. However, combination therapy did not provide additional benefits when used prophylactically. Autologous ASCs, alone or with metformin, proved most effective against late-stage RISF. Prophylactic intervention outperformed late therapy for mitigating radiation skin damage. Co-culture studies revealed that ASCs and metformin downregulated inflammation and fibrotic gene expression in both mouse and human fibroblasts.ConclusionsOur study suggests metformin's potential as a prophylactic measure to prevent RISF, and the combination of ASCs and metformin holds promise for late-stage RISF treatment. These findings have clinical implications for improving the quality of life for those affected by radiation-induced skin fibrosis.

Combination therapy of metformin and atorvastatin against benzopyrene-induced lung cancer via inflammatory signaling pathway.

The most prevalent cause of lung cancer is smoking tobacco, but exposure to second hand smoke, air pollution, and certain chemicals and substances at work can also raise the risk of disease. In this study, we scrutinized the chemoprotective effect of the metformin and atorvastatin combination against benzo[a]pyrene (BaP)-induced lung cancer in mice of Swiss albino. BaP (50 mg/kg) was used for induction of lung cancer and mice were treated with metformin, atorvastatin or their combination. Metformin + atorvastatin combination significantly (p< 0.001) improved the body weight, liver weight, suppressed the lung weight and tumor incidence and altered the levels of immunocompetent cells, polyamines, lung tumor markers, lung parameters and antioxidant parameters, respectively. Metformin + atorvastatin combination also suppressed cytokines levels, inflammatory parameters and caspase parameters. On the basis of the results, we can conclude that metformin + atorvastatin combination remarkably suppressed lung cancer via the inflammatory pathway.

Suspected case of erythema multiforme major caused by combination therapy of glimepiride, voglibose, and metformin with clomiphene citrate in a polycystic ovary syndrome and type 2 diabetes patient in India

Suspected case of erythema multiforme major caused by combination therapy of glimepiride, voglibose, and metformin with clomiphene citrate in a polycystic ovary syndrome and type 2 diabetes patient in India

Effectiveness and Safety of Sodium-Glucose Cotransporter2 Inhibitors Added to Dual or Triple Treatment in Patients with Type2 Diabetes Mellitus.

We evaluated the effectiveness and safety of sodium-glucose cotransporter2 inhibitor (SGLT2i) add-on treatment in patients with type2 diabetes mellitus (T2DM) in the real-world setting. This single-center retrospective study used the clinical database of Seoul National University Hospital in South Korea. Patients who received metformin monotherapy or combination therapy with ≥ 1 other oral hypoglycemic medication and had a baseline glycosylated hemoglobin (HbA1c) between 7.0% and 10.5% were included. Propensity score matching was applied between patients treated with and without SGLT2 inhibitors (SGLT2i and non-SGLT2i groups, respectively). Changes in HbA1c from baseline to week26 were compared between the SGLT2i and non-SGLT2i groups, and risk of adverse events (AE) were also assessed. A total of 1106 patients were included. At week26, HbA1c was significantly more reduced by 0.35 percentage points in the SGLT2i group than in the non-SGLT2i group (95%CI 0.30-0.41, P < 0.001). Likewise, the proportion of patients achieving HbA1c < 7% was also significantly higher (51.9% vs. 37.6%, P < 0.05) in the SGLT2i group than in the non-SGLT2i group. The risk of adverse events in the SGLT2i group was mostly comparable with those in the non-SGLT2i group except for diseases of the liver, pain, hypertensive diseases, and metabolic disorders, which showed significantly higher odds in the SGLT2i group. SGLT2i add-on treatment is an effective and safe therapeutic option for patients with T2DM in the real-world practice setting.

Combination therapy of metformin and morin attenuates insulin resistance, inflammation, and oxidative stress in skeletal muscle of high-fat diet-fed mice.

Lipid accumulation, inflammation, and oxidative stress are the most important causes of muscle insulin resistance. The aim of this study was to investigate the single and combined treatment effects of metformin (MET) and morin (MOR) on lipid accumulation, inflammation, and oxidative stress in the skeletal muscle of mice fed a high-fat diet. The mice were supplemented with MET (230 mg/kg diet), MOR (100 mg/kg diet), and MET + MOR for 9 weeks. Our results revealed that single treatment with MET or MOR, and with a stronger effect of MET + MOR combined treatment, reduced body weight gain, improved glucose intolerance and enhanced Akt phosphorylation in the muscle tissue. In addition, plasma and muscle triglyceride levels were decreased after treatment with MET and MOR. The expression of genes involved in macrophage infiltration and polarization and pro-inflammatory cytokines showed that MET + MOR combined treatment, significantly reduced inflammation in the muscle. Furthermore, combined treatment of MET + MOR with greater efficacy than the single treatment improved several oxidative stress markers in the muscle. Importantly, combined treatment of MET and MOR could increase the expression of nuclear factor erythroid 2-related factor 2, the master regulator of the antioxidant response. These findings suggest that combination of MET with MOR might ameliorate insulin resistance, inflammation, and oxidative stress in the skeletal muscle of mice fed high-fat diet.

Cost Utility Analysis Vildagliptin dan Glimepiride dalam Mencegah Komplikasi Mikrovaskuler menggunakan Model Markov

Microvascular complications can occur due to type 2 diabetes mellitus (DM). The cost of therapy increases due to the use of various antidiabetic drugs over a long period. This research is a pharmacoeconomic study that uses the Markov Model to compare costs and utilities in type 2 DM patients who receive metformin+glimepiride and metformin+vildagliptin therapy. Primary data was collected through the EQ5D questionnaire at Cirebon Harbor Hospital and secondary data (transition probability) was collected through a literature study. Characteristics of type 2 DM patients show that the majority of people suffering from this condition are aged between 55 and 59 years. Primary data from the hospital shows that the cost of therapy for controlled type 2 DM patients who receive combination therapy of metformin + glimepiride, and metformin + vildagliptin is Rp. 1,699,400, Rp. 5,807,786, and Rp. 10,100,426, respectively. Secondary data from articles treating type 2 DM shows that the 55-59 year age group is the largest. With an ICER of 61,493,943/QALYS, microvascular prevention in T2DM patients receiving the metformin+vildagliptin combination in Indonesia is considered effective and able to reduce the number of microvascular cases. This is based on the ICER value compared to the Indonesian Government's GDP, namely Rp. 71,030,183.3. This study shows that replacing glimepiride with vildagliptin for the prevention of microvascular complications is cost-effective and has better utility and effectiveness in reducing the incidence of microvascular complications. The use of vildagliptin can be recommended to reduce costs and the risk of microvascular complications.

Comparison of the efficacy of anti-diabetic medications as add-on to metformin in type 2 diabetes mellitus from a real-world database

BackgroundMetformin is recommended as a first-line drug in the guidelines of the treatment for type 2 diabetes mellitus. However, high-quality evidence from clinical trials directly comparing the degree of hypoglycemic effect of combination therapy of metformin and a hypoglycemic agent with a different mechanism of action with that of monotherapy of a hypoglycemic drug is lacking. We aimed to examine whether combination therapy of hypoglycemic agents with metformin showed antagonism, addition, or synergism compared to monotherapy with hypoglycemic agents other than metformin regarding hemoglobin A1c levels.MethodsThis retrospective cohort study used a medical information database in Japan. Non-insulin anti-hyperglycemic agents with different mechanisms of action were classified into eight drug classes. A monotherapy cohort and a combination therapy added to the metformin cohort were defined. The change in hemoglobin A1c levels was evaluated to compare the treatment effect between the cohorts.ResultsA total of 13,359 patients with type 2 diabetes mellitus in the monotherapy cohort and 1,064 in the metformin combination therapy cohort were identified. A comparison of the change from baseline HbA1c level by drug class between the two cohorts showed a similar trend. Among those treated with dipeptidyl peptidase-4 inhibitor and sodium-glucose co-transporter-2 inhibitor, no clinically significant difference was observed between the two cohorts (0.00% and -0.07% for unadjusted, 0.15% and -0.03% for propensity score matching-adjusted, and 0.09% and -0.01% for inverse probability treatment weighting-adjusted analysis).ConclusionsAccording to the results of this study, the effect of dipeptidyl peptidase-4 inhibitor or sodium-glucose co-transporter-2 inhibitor added to metformin seems to be additive with respect to the reduction in hemoglobin A1c.

A Study on Enhancing Pancreatic Islet Function in Type 2 Diabetes and Coronary Heart Disease Patients with Liraglutide and Metformin Combination Therapy

Objective: To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease. Methods: 60 patients with type 2 diabetes and coronary heart disease admitted from February 2022 to August 2023 were selected as research subjects. They were randomly assigned to either control or treatment groups, with 30 patients in each. The control group received metformin alone, while the treatment group received liraglutide in combination with metformin. Various indicators, including blood sugar levels, pancreatic islet function, and cardiac function between the two groups were compared. Results: The results of FPG, 2hPG, HbA1c, HOMA-IR, NT-proBNP, and LVEDD in the treatment group were lower than those in the control group, whereas the values of FINS, HOMA-β, E/A, and LVEF in the treatment group were higher than those in the control group (P &lt; 0.05). Conclusion: The use of liraglutide in combination with metformin significantly benefits patients with type 2 diabetes and coronary heart disease. It leads to improved pancreatic islet function, better blood sugar control, and enhanced cardiac function. This combination therapy is recommended for clinical adoption.

Regulation of Protein-Induced Apoptosis and Autophagy in Human Hepatocytes Treated with Metformin and Paclitaxel In Silico and In Vitro.

Metformin and paclitaxel therapy offer promising outcomes in the treatment of liver cancer. Combining paclitaxel with metformin enhances treatment effectiveness and mitigates the adverse effects associated with paclitaxel alone. This study explored the anticancer properties of metformin and paclitaxel in HepG2 liver cancer cells, MCF-7 breast cancer cells, and HCT116 colon cancer cells. The results demonstrated that the combination of these agents exhibited a lower IC50 in the tested cell lines compared to paclitaxel monotherapy. Notably, treating the HepG2 cell line with this combination led to a reduction in the G0/G1 phase and an increase in the S and G2/M phases, ultimately triggering early apoptosis. To further investigate the interaction between the cellular proteins with paclitaxel and metformin, an in silico study was conducted using proteins chosen from a protein data bank (PDB). Among the proteins studied, AMPK-α, EGFRK, and FKBP12-mTOR exhibited the highest binding free energy, with values of -11.01, -10.59, and -15.63 kcal/mol, respectively, indicating strong inhibitory or enhancing effects on these proteins. When HepG2 cells were exposed to both paclitaxel and metformin, there was an upregulation in the gene expression of AMPK-α, a key regulator of the energy balance in cancer growth, as well as apoptotic markers such as p53 and caspase-3, along with autophagic markers including beclin1 and ATG4A. This combination therapy of metformin and paclitaxel exhibited significant potential as a treatment option for HepG2 liver cancer. In summary, the combination of metformin and paclitaxel not only enhances treatment efficacy but also reduces side effects. It induces cell cycle alterations and apoptosis and modulates key cellular proteins involved in cancer growth, making it a promising therapy for HepG2 liver cancer.

Lack of Association of the HMGA1 Gene Variants with Metabolic Syndrome Risk and Response to Oral Anti-Diabetic Drugs

Background: Metabolic syndrome (Mets) is partially heritable. High mobility group AT-hook1 (HMGA1), an architectural transcription factor, affects the homeostasis of glucose. The marked inter-individual differences between T2DM patients in response to oral anti-diabetic drugs have become an issue for effective prescribing and dosing. The objective of this study was designed to assess whether different SNPs of the HMGA1 gene are associated with metabolic syndrome, and clarify the effect of these variants on response to combination therapy of metformin, sitagliptin, and glimepiride used by Mets with diabetes patients.&#x0D; Methods: From February until Augusts 2022, a total of 91 Iraqi participants (61 patients with metabolic syndrome and 30 controls). The diabetes patients were divided into two groups’ responders and non-responders, based on their HbA1c. Polymorphisms in HMGA1 and genotyping were identified by Sanger sequencing of genomic DNA.&#x0D; Results: The high prevalence of CC and GG genotypes of rs1023028442 and rs112081775 respectively was seen in the Iraqi population. Minor allele frequency of rs1023028442 was higher among metabolic patients without diabetes with (MAF=0.08) compared to the control group with (MAF= 0%). While (MAF=0.1) of rs112081775 was seen in metabolic patients without diabetes compared to (MAF=0.02) in the control group. The non-significant difference in genotyping and allele carriage frequencies of the HMGA1 gene was seen between total metabolic syndrome patients and the control group. Based on their response to therapy non-significant difference was seen between those with wild and carrier genotypes.&#x0D; Conclusions: This study suggests a lack of association of the rare HMGA1 gene variants with metabolic syndrome risk and response to oral anti-diabetic drugs.

Investigating the Insulin Sensitizing Effects of Metformin and Myo-Inositol in Polycystic Ovary Syndrome: A Randomized Controlled Trial Protocol

Introduction: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by ovulatory dysfunction, hyperandrogenism, and metabolic dysregulation. Insulin resistance (IR) is a common hallmark of PCOS and contributes to metabolic dysfunction. A combination of lifestyle changes and symptom management treatments can help manage the condition. Metformin and myo-inositol (MI) have been shown to improve insulin sensitivity and reduce excess androgen levels in women with PCOS, but there is a lack of research on the effects of combinatory therapy of MI and metformin. This study aims to investigate the hypothesis that a combination of MI and metformin will result in improved insulin sensitivity and clinical outcomes of PCOS. Methods: The study is a double-blinded, randomized controlled trial examining 60 women diagnosed with PCOS that demonstrate the presence of IR. Participants are randomized to one of the following treatments over a six-month period: metformin (MET), inositol (INO), combined metformin and inositol (MET-INO) or placebo-control (CON). BMI, LH:FSH ratio, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were assessed at day 0, day 84 and day 168. Anticipated Results: It is anticipated that the MET-INO group will have the most profound effects following intervention, with a decrease in BMI by 3-4%, a decrease in LH:FSH ratio by 30-40%, and a decrease in HOMA-IR by 1-1.5. MET group is expected to have a significant decrease in BMI by 2-3%, a decrease in LH:FSH ratio by 20-30%, and a decrease in HOMA-IR by 0.5-1.5. The INO group is anticipated to experience a significant decrease in BMI by 1-2%, a decrease in LH:FSH ratio by 10-20%, and a decrease in HOMA-IR by 0.2-0.4. Conclusion: The findings of this study suggest that a combination therapy of metformin and MI may offer a more effective treatment option for improving insulin sensitivity in women with PCOS, compared to metformin or inositol treatment alone. These results have important implications for patients with PCOS and clinicians managing their care. Future studies should further investigate the effectiveness and long-term effects of these treatments.

Influence of rutin and its combination with metformin on vascular functions in type 1 diabetes

The present work examined the effect of oral administration of rutin and its combination with metformin, an antidiabetic drug on blood glucose, total cholesterol and triglycerides level and vascular function in streptozotocin (STZ) -induced diabetic rats. Male Sprague Dawley rats were rendered diabetic by a single intraperitoneal injection of STZ (50 mg/kg). Rutin and metformin were orally administered to diabetic rats at a dose of 100 mg/kg and 300 mg/kg body weight/day, respectively, for 4 weeks. Plasma analysis was conducted to determine changes in the plasma glucose and lipid levels. Rat aortic ring reactivity in response to endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) relaxants, and to the α1-adrenergic agonist phenylephrine (PE) were recorded. Histology of pancreas, liver and kidney were evaluated. In results, rutin and metformin alone and in combination has led to significant improvements in blood glucose, cholesterol and triglyceride levels compared to diabetic group. Diabetic aortic rings showed significantly greater contraction in response to PE, and less relaxation in response to ACh and SNP. Treatment with rutin and metformin in combination significantly reduced PE-induced contraction and increased ACh-induced and SNP-induced relaxation in diabetes when compared to rutin or metformin alone. Significant histological improvements were seen with combination therapy. In conclusion, rutin and metformin combination therapy has the most potentiality for restoring blood glucose and lipid level as well as vascular function.

Combination of Pioglitazone and Metformin Actions on Liver Lipid Metabolism in Obese Mice.

Despite the increasing prevalence rate of nonalcoholic fatty liver disease (NAFLD) worldwide, efficient pharmacotherapeutic regimens against NAFLD still need to be explored. Previous studies found that pioglitazone and metformin therapy could partly ameliorate NAFLD, but their combination therapy effects have not been researched. In the present study, we assessed the protective effects of metformin and pioglitazone combination therapy on liver lipid metabolism in high-fat diet (HFD)-fed mice and investigated the molecular mechanism. Male C57BL/6 mice were divided into five groups: normal control; HFD control; metformin monotherapy; pioglitazone monotherapy and combined therapy. After 8 weeks of pharmacological intervention, glucose and lipid metabolism characteristics, hepatic histology, lipidomics profiling and RNA-seq analysis were performed. The combination of pioglitazone and metformin significantly ameliorated HFD-induced metabolic disturbance and the hepatic oil red O area. A lipidomics analysis showed that combined therapy could significantly reduce the high levels of free fatty acids (FFA), diacylglycerol and triglycerides, while a set of glycerophospholipids and sphingolipids were increased in the combined therapy group. Consistently, an RNA-seq analysis also showed a remarkable reduction in genes associated with FFA uptake and de novo lipogenesis, including Cd36, Fads1, Fads2, Fasn, Scd1, Elovl5 and Pklr in the combined therapy group. Pioglitazone and metformin might have a synergistic protective effect on NAFLD by improving hepatic lipid profiles in HFD-induced mice. Further studies are needed to verify the clinical effects.

Type 2 diabetes clusters in the Novosibirsk region

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a heterogeneous disease. Determination of different T2DM phenotypes will improve the prediction of metabolic disorders, the risk of complications and individual diabetes therapy.AIM: To identify clusters of T2DM in patients with different duration of diabetes with a study of the frequency of diabetic complications and drug therapy in the Novosibirsk region.MATERIALS AND METHODS: The study was carried out at Diamodul in the period 2013–2017 in the Novosibirsk region. K-means cluster analysis was performed in 2805 T2DM patients aged 44 to 75 years with a duration of diabetes of 7.84±6.53 years based on 5 variables — HbA1c, age at diagnosis, BMI, C-peptide, sex.RESULTS: Cluster analysis identified three clusters: cluster 1 in 1003 patients (35.7%) with preserved β-cell function, age of T2DM diagnosis 51.72±8.29 years and BMI 33.50±5.74 kg/m2, in men there was a 27% higher risk of developing diabetic nephropathy compared to women. Cluster 2 in 432 patients (15.4%) with increased function of β-cells, the age of diagnosis of T2DM was older — 52.91±7.75 years, patients had a higher BMI of 35.64±7.21 kg/m2 and more high diastolic blood pressure, earlier development of diabetic retinopathy, nephropathy and polyneuropathy, and better response to metformin therapy and combined therapy with metformin and sulfonylurea. Cluster 3 in 1370 patients (48.8%) with reduced function of β-cells, the age of diagnosing T2DM was younger — 49.63±8.32 years, patients had a lower BMI of 33.09±6.36 kg/m2 and had longer diabetes, high fasting glucose levels, males were associated with a higher risk of developing diabetic nephropathy (by 26%) compared with women, the first line of therapy was insulin therapy in 52.8% of patients.CONCLUSION: The conducted study in T2DM patients with different duration of diabetes confirmed the possibility of using cluster analysis to identify phenotypes of T2DM in the Russian population by five variables (HbA1c, age at the time of diagnosis, BMI, C-peptide, gender). A high incidence of early development of diabetic polyneuropathy, nephropathy and retinopathy was revealed in a cluster with increased function of β-cells, male gender was risk factor for diabetic nephropathy and polyneuropathy.

864-P: Effects on Glycemic Control by Combination Therapy of Gliclazide-Metformin and Insulin in Type 2 Diabetes Mellitus Patients

Background: Diabetes mellitus is most common non-communicable diseases. Purpose of this study was to observe the effects on glycemic control by combination therapy of gliclazide-metformin and insulin in type 2 diabetes mellitus patients according to baseline HbA1c, fasting blood glucose (FBG) and blood glucose 2 hours after breakfast. Methods: An observational study was conducted at Endocrinology Outpatient Department of Dhaka Medical College Hospital, Dhaka and Outpatient Department of Ibrahim General Hospital, Mirpur, Dhaka over a period of one year (July 2018 to June 2019). Total 110 type 2 diabetic patients were selected purposively. The patients were divided into two groups. In group I, 55 patients treated with gliclazide (80mg) and metformin (500mg) combination therapy twice daily for consecutive 12 weeks and in group II, 55 patients treated with Insulin (premixed 30/70) twice daily for consecutive 12 weeks. Results: After 12 weeks of treatment HbA1c level reduced from (mean ± SD) 8.94 ± 0.91 to 7.82 ± 1.86 in group I and 10.07 ± 1.28 to 7.90 ± 1.01in group II. FBG level reduced from 10.05 ± 1.57 to 7.96 ± 1.62 in group I and 11.61 ± 2.62 to 7.60 ± 1.23 in group II. Blood glucose 2 hours ABF level reduced from 14.00 ± 2.04 to10.99 ± 1.41 in group I and 16.70 ± 3.61to 10.71 ± 1.52 in group II. In group I, 36.4% patients achieved HbA1c target level, 40% patients achieved FBG target level and 25.5% patients achieved blood glucose 2 hrs ABF target level. In group II, 29.1% patients achieved HbA1c target level, 56.4% patients achieved FBG target level and 29.1% patients achieved blood glucose 2 hrs ABF target level Conclusion: This study showed improvement in the overall glycemic control (HbA1c, FBG and blood sugar 2hours ABF) during the study period. Both groups of drugs are effective in controlling blood glucose but individual group has unique beneficial effect. Key words: Type 2 diabetes mellitus, Glycemic control, Glicazide-Metformin Disclosure M.Saifuddin: None.