Title | Abstract | Num Citations | Date | Authors | Link |
Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial | Background: Combining metformin (XR) with dapagliflozin to initiate pharmacotherapy in patients with type 2 diabetes (T2D) and high baseline HbA1c may be advantageous. We conducted two randomised, double-blind, three-arm 24-week trials in treatment-naïve patients to compare dapagliflozin plus metformin, dapagliflozin alone and metformin alone. Methods: Eligible patients had baseline HbA1c 7.5–12%. Each trial had three arms: dapagliflozin plus metformin, dapagliflozin monotherapy and metformin monotherapy. Dapagliflozin in combination and as monotherapy was dosed at 5 mg (Study 1) and 10 mg (Study 2). Metformin in combination and as monotherapy was titrated to 2000 mg. The primary endpoint was HbA1c change from baseline; secondary endpoints included change in fasting plasma glucose (FPG) and weight. Results: In both trials, combination therapy led to significantly greater reductions in HbA1c compared with either monotherapy: −2.05 for dapagliflozin + metformin, −1.19 for dapagliflozin, and −1.35 for metformin (p < 0.0001) (Study 1); −1.98 for dapagliflozin + metformin, −1.45 for dapagliflozin and −1.44 for metformin (p < 0.0001) (Study 2). Combination therapy was statistically superior to monotherapy in reduction of FPG (p < 0.0001 for both studies); combination therapy was more effective than metformin for weight reduction (p < 0.0001). Dapagliflozin 10 mg was non-inferior to metformin in reducing HbA1c (Study 2). Events suggestive of genital infection were reported in 6.7%, 6.9% and 2.0% (Study 1) and 8.5%, 12.8% and 2.4% (Study 2) of patients in combination, dapagliflozin and metformin groups; events suggestive of urinary tract infection were reported in 7.7%, 7.9% and 7.5% (Study 1) and 7.6%, 11.0% and 4.3% (Study 2) of patients in the respective groups. No major hypoglycaemia was reported. Conclusion: In treatment-naïve patients with T2D, dapagliflozin plus metformin was generally well tolerated and effective in reducing HbA1c, FPG and weight. Dapagliflozin-induced glucosuria led to an increase in events suggestive of urinary tract and genital infections. | 198 | 13 March 2012 | R. R. Henry,A. V. Murray,M. H. Marmolejo,D. Hennicken,A. Ptaszynska,J. F. List | https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1742-1241.2012.02911.x |
Metformin: an old but still the best treatment for type 2 diabetes | The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have contributed to the decrease of adverse cardiovascular outcomes otherwise not attributable to metformin’s mere antihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently launched, introducing the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is increasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a neuroprotective effect. Metformin’s negligible risk of hypoglycemia in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an appropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an extended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin resistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes, cancer, and neuroprotection. | 289 | Feb 2013 | Lilian Beatriz Aguayo Rojas & Marilia Brito Gomes | https://dmsjournal.biomedcentral.com/articles/10.1186/1758-5996-5-6 |
Metformin: a review of its potential indications | Metformin is the most commonly prescribed drug for type 2 diabetes mellitus. In recent years, in addition to glucose lowering, several studies have presented evidence suggesting some potential role for metformin, such as antitumor effect, antiaging effect, cardiovascular protective effect, neuroprotective effect or an optional treatment for polycystic ovary syndrome. This paper will critically review the role of metformin to provide reference for doctors and researchers. | 114 | Aug 2017 | Yi-Wei Wang,#1,* Si-Jia He,#1,* Xiao Feng,1 Jin Cheng,1 Yun-Tao Luo,1 Ling Tian,2 and Qian Huang1 | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574599/ |
Metformin and Aging: A Review | Metformin is sometimes proposed to be an “anti-aging” drug, based on preclinical experiments with lower-order organisms and numerous retrospective data on beneficial health outcomes for type 2 diabetics. Large prospective, placebo-controlled trials are planned, in pilot stage or running, to find a new use (or indication) for an aging population. As one of the metformin trials has “frailty” as its endpoint, similar to a trial with a plant-derived senolytic, the latter class of novel anti-aging drugs is briefly discussed. Concerns exist not only for vitamin B12 and B6 deficiencies, but also about whether there are adverse effects of metformin on individuals who try to remain healthy by maintaining cardiovascular fitness via exercise. | 44 | Sep 2019 | Glossmann H.H.a · Lutz O.M.D.b | https://www.karger.com/Article/FullText/502257 |
Metformin acutely lowers blood glucose levels by inhibition of intestinal glucose transport | Metformin is currently the most prescribed drug for treatment of type 2 diabetes mellitus in humans. It has been well established that long-term treatment with metformin improves glucose tolerance in mice by inhibiting hepatic gluconeogenesis. Interestingly, a single dose of orally administered metformin acutely lowers blood glucose levels, however, little is known about the mechanism involved in this effect. Glucose tolerance, as assessed by the glucose tolerance test, was improved in response to prior oral metformin administration when compared to vehicle-treated mice, irrespective of whether the animals were fed either the standard or high-fat diet. Blood glucose-lowering effects of acutely administered metformin were also observed in mice lacking functional AMP-activated protein kinase, and were independent of glucagon-like-peptide-1 or N-methyl-D-aspartate receptors signaling. [18F]-FDG/PET revealed a slower intestinal transit of labeled glucose after metformin as compared to vehicle administration. Finally, metformin in a dose-dependent but indirect manner decreased glucose transport from the intestinal lumen into the blood, which was observed ex vivo as well as in vivo. Our results support the view that the inhibition of transepithelial glucose transport in the intestine is responsible for lowering blood glucose levels during an early response to oral administration of metformin. | 29 | Apr 2019 | Olga Horakova, Petra Kroupova, Kristina Bardova, Jana Buresova, Petra Janovska, Jan Kopecky & Martin Rossmeisl | https://www.nature.com/articles/s41598-019-42531-0 |
Sustained efficacy of dapagliflozin when added to metformin in type 2 diabetes inadequately controlled by metformin monotherapy | Background and aims: The selective SGLT2 inhibitor dapagliflozin (DAPA) reduces hyperglycaemia independently of insulin secretion or action by inhibiting renal glucose reabsorption. This study (MB102014) is a randomised double-blind, placebo (PBO)-controlled trial of DAPA added to metformin (MET) in T2DM (n=546) inadequately controlled with MET alone. Previously reported short-term data at week 24 showed significant mean reductions in the primary [HbA1c] and secondary [fasting plasma glucose (FPG) and weight] endpoints with DAPA compared to PBO. Here we report efficacy and safety results at week 102 of the long-term extension. Materials and methods: Patients aged 18-77 years with HbA1c 7-10% received DAPA 2.5 mg, 5 mg, 10 mg or PBO, plus open-label MET (≥1500mg/d). Exploratory endpoints at week 102 included changes from baseline in HbA1c, FPG and weight, and were analyzed by longitudinal repeated measures analysis. Results: Overall 71.2% of patients completed 102 weeks of the study; fewer on PBO (63.5%) than on DAPA 2.5 mg, 5 mg, and 10 mg (68.3%, 73.0%, 79.8%), due mainly to more patients on PBO discontinuing for lack of efficacy. At week 102, all DAPA groups showed greater mean reductions from baseline in HbA1c, FPG and weight compared to PBO (table), effects that were similar to those observed at week 24 and maintained throughout the trial. More patients at week 102 also achieved a therapeutic response of HbA1c<7% with DAPA 2.5 mg, 5 mg, and 10 mg (20.7%, 26.4%, 31.5%) than with PBO (15.4%). Adverse events (AEs), serious AEs and AEs leading to discontinuation were balanced across all groups. Signs and symptoms suggestive of genital infection (GenInf) were reported in 11.7%, 14.6%, 12.6% (DAPA 2.5 mg, 5 mg, 10 mg) and 5.1% (PBO) of patients, with 1 discontinuation due to GenInf. Signs and symptoms suggestive of urinary tract infection (UTI) were reported in 8.0%, 8.8%, 13.3% (DAPA 2.5 mg, 5 mg, 10 mg) and 8.0% (PBO), with 1 discontinuation due to UTI. No event of pyelonephritis was reported. Conclusion: In comparison to PBO, DAPA added to MET over 102 weeks demonstrated greater and sustained improvements in glycaemic control, clinically meaningful reduction in weight, and no increased risk of hypoglycaemia in patients with T2DM inadequately controlled with MET alone. | Sep 2011 | C.J. Bailey, J.L. Gross, M. Yadav, N. Iqbal, T.A. Mansfield, J.F. List | https://research.aston.ac.uk/en/publications/sustained-efficacy-of-dapagliflozin-when-added-to-metformin-in-ty | |
Research Article Metformin Treatment in Type 2 Diabetes in Pregnancy: An Active Controlled, Parallel-Group, Randomized, Open Label Study in Patients with Type 2 Diabetes in Pregnancy | Aims: To assess the effect of metformin and to compare it with insulin treatment in patients with type 2 diabetes in pregnancy in terms of perinatal outcome, maternal complications, additional insulin requirement, and treatment acceptability. Methods: In this randomized, open label study, 206 patients with type 2 diabetes in pregnancy who met the eligibility criteria were selected from the antenatal clinics. Insulin was added to metformin treatment when required, to maintain the target glycemic control. The patients were followed up till delivery. Maternal, and perinatal outcomes and pharmacotherapeutic characteristics were recorded on a proforma. Results: Maternal characteristics were comparable in metformin and insulin treated group. 84.9% patients in metformin group required add-on insulin therapy at mean gestational age of 26.58 ± 3.85 weeks. Less maternal weight gain (P < 0.001) and pregnancy induced hypertension (P = 0.029) were observed in metformin treated group. Small for date babies were more in metformin group (P < 0.01). Neonatal hypoglycemia was significantly less and so was NICU stay of >24 hours in metformin group (P < 0.01). Significant reduction in cost of treatment was found in metformin group. Conclusion: Metformin alone or with add-on insulin is an effective and cheap treatment option for patients with type 2 diabetes in pregnancy | 47 | 1 Mar 2015 | Jahan Ara Ainuddin, Nasim Karim, Bahria University, Sidra Zaheer, Syed Sanwer, Anjum Ara Hasan | https://www.researchgate.net/publication/274256703_Research_Article_Metformin_Treatment_in_Type_2_Diabetes_in_Pregnancy_An_Active_Controlled_Parallel-Group_Randomized_Open_Label_Study_in_Patients_with_Type_2_Diabetes_in_Pregnancy |
Metformin in 2019 | Metformin is the first-line pharmacologic treatment for type 2 diabetes and the most commonly prescribed drug for this condition worldwide, either alone or in combination with insulin or other glucose-lowering therapies. Metformin is a biguanide, a drug class of herbal origin that has been widely used to treat diabetes since the 1950s.¹,2 Two other biguanides were withdrawn from clinical use because they caused lactic acidosis. Metformin was also taken off the US market due to concerns over lactic acidosis, but it subsequently has been proven safe and effective in lowering glucose levels and was reintroduced in 1995. Optimal metformin use requires clear understanding of its effects, dosing, safety, and alternatives. | 66 | 1 Apr 2019 | James Flory, Kasia Lipska | https://www.researchgate.net/publication/332583769_Metformin_in_2019 |
Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes | Objective: The purpose of this study was to evaluate the efficacy and safety of sitagliptin as an add-on to metformin therapy in patients with moderately severe (hemoglobin A1c ≥ 8.0% and ≤ 11.0%) type 2 diabetes mellitus (T2DM). Research design and methods: This was a multinational, randomized, placebo-controlled, parallel-group, double-blind study conducted in 190 patients with T2DM. After ≥ 6 weeks of stable metformin monotherapy (≥ 1500 mg/day), patients were randomized to either the addition of sitagliptin 100 mg once daily or placebo to ongoing metformin for 30 weeks. Main outcome measures: The primary efficacy endpoint was reduction in hemoglobin A1c (HbA1c) measured after 18 weeks of sitagliptin treatment. Key secondary endpoints included reduction in fasting plasma glucose (FPG) and 2-hour (2-h) postprandial plasma glucose (PPG) at 18 weeks, and HbA1c at 30 weeks. The proportion of patients meeting the goal of HbA1c < 7.0% was also analyzed. Results: Sitagliptin significantly reduced HbA1c, FPG, and 2-h PPG, compared with placebo (all p < 0.001). The net improvement in HbA1c was –1.0% at both 18 and 30 weeks, and a significantly greater proportion of patients treated with sitagliptin achieved HbA1c < 7.0% by the end of the study (22.1% vs. 3.3%, p < 0.001). Sitagliptin was well-tolerated. Compared with placebo, sitagliptin had a neutral effect on body weight and did not significantly increase the risk of hypoglycemia or gastrointestinal adverse events. Conclusions: Addition of sitagliptin 100 mg once daily to ongoing metformin therapy was well-tolerated and resulted in significant glycemic improvement in patients with moderately severe T2DM who were treated for 30 weeks. | 11 Jan 2008 | Itamar Raz,Yu Chen,Mei Wu,Shehla Hussain,Keith D. Kaufman,John M. Amatruda,Ronald B. Langdon,Peter P. Stein &Maria Alba | https://www.tandfonline.com/doi/abs/10.1185/030079908X260925 | |
Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial | Background Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population. Methods This was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (≥1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight. Results A total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P <0.0001), and -0.78% (P <0.0001) for dapagliflozin 2.5 to 5, and 10 mg, respectively. In addition, all dapagliflozin groups had sustained reductions from baseline in FPG (-1.07 to -1.47 mmol/l) and body weight (-1.10 to -1.74 kg) at 102 weeks, whereas increases were noted in placebo-treated patients for both of these outcomes. Events of hypoglycemia were rare and were not severe. Evidence suggestive of genital infection was reported in 11.7% to 14.6% of dapagliflozin patients and 5.1% of placebo patients, with one related discontinuation (dapagliflozin 5 mg). Evidence suggestive of urinary tract infection was reported in 8.0% to 13.3% of dapagliflozin patients and 8.0% of placebo patients, with one related discontinuation (dapagliflozin 2.5 mg). Conclusions Dapagliflozin added to metformin for 102 weeks enabled sustained reductions in HbA1c, FPG, and weight without increased risk of hypoglycemia in patients with type 2 diabetes who were inadequately controlled on metformin alone. | 20 February 2013 | Clifford J Bailey, Jorge L Gross, Delphine Hennicken, Nayyar Iqbal, Traci A Mansfield & James F List | https://link.springer.com/article/10.1186/1741-7015-11-43 | |
Metformin: A review of its use in the treatment type 2 diabetes | Metformin is now the most widely prescribed oral hypoglycemic agent. This review outlines its use in the treatment of type 2 diabetes. The main mechanisms of action include reduction of appetite and of intestinal carbohydrate absorption, inhibition of hepatic gluconeogenesis, and increased glucose uptake by peripheral tissues. Metformin has been established as the drug of choice for the first-line treatment of type 2 diabetes. According to broadly accepted guidelines, it should be administered early at diagnosis of this metabolic disorder, alongside diet and exercise. This agent may also be safely and efficaciously combined with all other oral hypoglycemic agents, enabling a useful additive effect. Additionally, it may be prescribed in conjunction with insulin. This combination aims to offset insulin resistance, reduce insulin requirements and minimize weight gain. Of greater importance, metformin has been consistently shown to have a favorable effect on cardiovascular risk factors and to improve cardiovascular outcomes. Interestingly, the efficacy of metformin is accompanied by excellent safety: caution is only needed to avoid the drug in patients with obvious contraindications (mainly chronic renal failure, congestive heart failure, chronic obstructive pulmonary disease, liver disease). Moreover, the cost-effectiveness of metformin has been established. Generally, metformin is an excellent choice both in the specialized setting and in primary health care. | 26 | January 2009 | N. Papanas, Efstratios Maltezos | https://www.researchgate.net/publication/303198715_Metformin_A_review_of_its_use_in_the_treatment_type_2_diabetes |
Metformin: New understandings, new uses | Metformin, a biguanide, has been available in the US for the treatment of type 2 diabetes mellitus for nearly 8 years. Over this period of time, it has become the most widely prescribed antihyperglycaemic agent. Its mechanism of action involves the suppression of endogenous glucose production, primarily by the liver. Whether the drug actually has an insulin sensitising effect in peripheral tissues, such as muscle and fat, remains somewhat controversial. Nonetheless, because insulin levels decline with metformin use, it has been termed an 'insulin sensitiser'. Metformin has also been shown to have several beneficial effects on cardiovascular risk factors and it is the only oral antihyperglycaemic agent thus far associated with decreased macrovascular outcomes in patients with diabetes. Cardiovascular disease, impaired glucose tolerance and the polycystic ovary syndrome are now recognised as complications of the insulin resistance syndrome, and there is growing interest in the management of this extraordinarily common metabolic disorder. While diet and exercise remain the cornerstone of therapy for insulin resistance, pharmacological intervention is becoming an increasingly viable option. We review the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits it provides over and above its effect on glucose levels alone. We also discuss its potential role for a variety of insulin resistant and prediabetic states, including impaired glucose tolerance, obesity, polycystic ovary syndrome and the metabolic abnormalities associated with HIV disease. | 258 | February 2003 | Ripudaman S Hundal, Silvio Inzucchi | https://www.researchgate.net/publication/10604640_Metformin_New_understandings_new_uses |
The mechanisms of action of metformin | Metformin is a widely-used drug that results inclear benefits in relation to glucose metabolism anddiabetes-related complications. The mechanisms underlyingthese benefits are complex and still not fully understood.Physiologically, metformin has been shown to reduce hepaticglucose production, yet not all of its effects can be explainedby this mechanism and there is increasing evidence of a keyrole for the gut. At the molecular level the findings vary de-pending on the doses of metformin used and duration of treat-ment, with clear differences between acute and chronic admin-istration. Metformin has been shown to act via both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms; by inhibition of mitochondrial res-piration but also perhaps by inhibition of mitochondrial glyc-erophosphate dehydrogenase, and a mechanism involving thelysosome. In the last 10 years, we have moved from a simplepicture, that metformin improves glycaemia by acting on theliver via AMPK activation, to a much more complex picturereflecting its multiple modes of action. More work is requiredto truly understand how this drug works in its target popula-tion: individuals with type 2 diabetes | 834 | 3 August 2017 | Graham Rena, David G Hardie, Ewan R Pearson | https://www.researchgate.net/publication/318928248_The_mechanisms_of_action_of_metformin |
Metformin in patients with and without diabetes: A paradigm shift in cardiovascular disease management | With an increasing global burden of coronary artery disease (CAD), early detection and timely management of risk factors are crucial to reduce morbidity and mortality in such patients. Diabetes mellitus (DM) is considered an inde-pendent risk factor for the development of CAD. Metformin, an anti-diabetic drug, has been shown in pre-clinical and clinical studies, to lower the cardiovascular events in the DM patients. Growing evidence suggests that metformin has a protective effect on coronary artery beyond its hypoglycemic effects. Given its global availability, route of adminis-tration and cost, metformin provides an alternate/additional therapeutic option for primary and secondary preven-tion of CAD in DM and non-diabetics alike. Future prospective cohort-based studies and randomized clinical trials are needed to identify ‘at-risk’ population who may potentially benefit from metformin | 49 | April 2019 | Fei Luo, Avash Das, Jingfei Chen, Panyun Wu, Xiangping Li, Zhenfei Fang | https://www.researchgate.net/publication/332716445_Metformin_in_patients_with_and_without_diabetes_A_paradigm_shift_in_cardiovascular_disease_management |
Metformin Hydrochloride in the Treatment of Type 2 Diabetes Mellitus: A Clinical Review with a Focus on Dual Therapy | Type 2 diabetes mellitus typically involves abnormal beta-cell function that results in relative insulin deficiency, insulin resistance accompanied by decreased glucose transport into muscle and fat cells, and increased hepatic glucose output, all of which contribute to hyperglycemia. This review examines the pharmacology, pharmacokinetics, drug-interaction potential, adverse effects, and dosing guidelines for metformin hydrochloride, a biguanide agent for the treatment of type 2 diabetes. Clinical trial data are reviewed, including efficacy and tolerability information, with a focus on studies of dual metformin therapy (metformin plus another oral agent or insulin) published from 1998 to the present. Pharmacoeconomic considerations are also discussed. Primary research and review articles were identified through a search of MEDLINE (1966-May 2003) and International Pharmaceutical Abstracts (1970-May 2003) using the terms metformin and/or Glucophage. Web of Science (1995-May 2003) was used to search for additional abstracts. The package inserts for metformin and metformin combination products were consulted. All identified articles and abstracts were assessed for relevance, and all relevant information was included. Priority was given to the primary medical literature and clinical trial reports. Metformin is the only currently available oral antidiabetic/hypoglycemic agent that acts predominantly by inhibiting hepatic glucose release. Because patients with type 2 diabetes often have excess hepatic glucose output, use of metformin is effective in lowering glycosylated hemoglobin (HbA1c) by 1 to 2 percentage points when used as monotherapy or in combination with other blood glucose-lowering agents or insulin. Other metabolic variables (eg, dyslipidemia, fibrinolysis) may be improved with the use of metformin. Body weight is often maintained or slightly reduced from baseline. Metformin is well tolerated and is associated with few clinically deleterious adverse events. The most important and potentially life-threatening adverse event associated with its use is lactic acidosis, which occurs very rarely. Metformin has multiple benefits in patients with type 2 diabetes. It can effectively lower HbA1c values, positively affect lipid profiles, and improve vascular and hemodynamic indices. Adverse effects are generally tolerable and self-limiting. The availability of products combining metformin with a sulfonylurea or rosiglitazone has expanded the array of therapies for the management of type 2 diabetes. | 161 | January 2004 | Stephen M Setter, Jason L Iltz, Jason Thams, R Keith Campbell | https://www.researchgate.net/publication/8898351_Metformin_Hydrochloride_in_the_Treatment_of_Type_2_Diabetes_Mellitus_A_Clinical_Review_with_a_Focus_on_Dual_Therapy |
Metformin and the Incidence of Cancer in Patients With Diabetes: A Nested Case-Control Study | Diabetes is asso ciated with an in-creased risk of vario us forms ofcancer, such as cancer of the liver,colon, pancreas, breast, bladder, and kid-ney. Metformin, widely given to patientswith type 2 diabetes, works by inhibit-in g hepatic glucose production throughan LKB1 (serine-threonine liver kinaseB1)/AMP-activated protein kinase (AMPK)–mediated mechanism. LKB1 is a well-recognized tumor suppressor. Activationof AMPK by LKB1 plays an importantrole in inhibiting cell growth. It has beensuggested that metformin use in patientswith diabetes may reduce their risk ofcancer (1). Some studies have reportedthat diabetic patients taking metforminshowed decreased cancer risk (2,3). How-ever, several studies have shown thatmetformin does not reduce the r isk ofcancer in patients with diabetes (4,5). Lit-tle information is available on the subjectconsidering non-Caucasian ethnicity. Weused representati ve National Hea lth In-surance datasets for Taiwan to form a co-hort to assess the total number of cancerincidences in relation to metformin useamong dia betic patients. | 23 | September 2013 | Shu-Yi Wang, Chieh-Sen Chuang, Chih-Hsin Muo, Shih-Te Tu, Ming-Chia Mellissa Lin, Fung-Chang Sung, Chia-Hung Kao | https://www.researchgate.net/publication/256085881_Metformin_and_the_Incidence_of_Cancer_in_Patients_With_Diabetes_A_Nested_Case-Control_Study |
Metformin and glitazones: Does similarity in biomolecular mechanism originate from tautomerism in these drugs? | This theoretical study attempts to find out similarity between metformin and glitazone class of antidiabetic drugs. It was found that some tautomeric forms of both metformin and thiazolidinedione ring of glitazones have similar molecular electrostatic potential (MESP) surface and may bind to a common complementary surface. Complexation and docking studies were also carried out in order to support this hypothesis. | 16 | January 2008 | Sandeep Sundriyal, Smriti Khanna, Rikta Saha, Prasad V Bharatam | https://www.researchgate.net/publication/202228609_Metformin_and_glitazones_Does_similarity_in_biomolecular_mechanism_originate_from_tautomerism_in_these_drugs |
Safety and Efficacy of Sitagliptin-Metformin in Fixed Combination for the Treatment of Type 2 Diabetes Mellitus | The biguanide, metformin, is considered rst-line treatment for type 2 diabetes. Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor acts through the incretin pathway and has a glucose dependent mode of action. The complementary hypoglycemic properties of these drugs make xed dose combination treatment an attractive prospect. Evidence from recent clinical trials suggests a benecial effect of the combination on efcacy, demonstrated by signicant improvement of hemoglobin A1c (HbA1c), fasting and postprandial glucose levels. The xed dose combination is likely to have greater patient tolerability compared with monotherapy with either agent because of low rates of hypoglycemia, weight neutrality, and lower rates of side effects. High acquisition cost and paucity of long-term safety data are, however, potential barriers to their wider use. An overview of the pharmacology and clinical outcomes from recent trials of the metformin-sitagliptin combination and how the combination could t into the type 2 diabetes treatment algorithm is presented in this review | 9 | September 2013 | Chitrabhanu Ballav, Stephen Gough | https://www.researchgate.net/publication/256541837_Safety_and_Efficacy_of_Sitagliptin-Metformin_in_Fixed_Combination_for_the_Treatment_of_Type_2_Diabetes_Mellitus |