Metformin: Myths, Misunderstandings and Lessons from History
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Use of Metformin in the Setting of Mild-To-Moderate Renal Insufficiency
Reviews/Commentaries/ADA Statements REVIEW Use of Metformin in the Setting of Mild-to-Moderate Renal Insufficiency 1 KASIA J. LIPSKA, MD hepatic gluconeogenesis without raising 2 CLIFFORD J. BAILEY, PHD, FRCP fi 3 insulin levels, it rarely leads to signi cant SILVIO E. INZUCCHI, MD hypoglycemia when used as a monother- apy (8,11). As a result, metformin is widely considered an ideal first-line agent for the treatment of type 2 diabetes, as common clinical conundrum faces despite multiple trials of intensive glu- recommended by several clinical guide- all U.S. practitioners treating pa- cose control using a variety of glucose- lines (12–14). A fi tients with type 2 diabetes. Today’s lowering strategies, there is a paucity of In addition to such bene ts, metfor- U.S. Food and Drug Administration pre- data to support specificadvantageswith min reduces the risk of developing di- scribing guidelines for metformin contra- other agents on cardiovascular outcomes abetes in individuals at high risk for the indicate its use in men and women with (5–7). disease (15) and has been considered as a serum creatinine concentrations $1.5 In the original UK Prospective Di- reasonable “off-label” approach in se- and $1.4 mg/dL ($132 and $123 abetes Study (UKPDS), 342 overweight lected individuals for diabetes prevention mmol/L), respectively. In a patient toler- patients with newly diagnosed diabetes (16). ating and controlled with this medication, were randomly assigned to metformin should it automatically be discontinued therapy (8). After a median period of 10 — as the creatinine rises beyond these cut years, this subgroup experienced a 39% HISTORICAL PERSPECTIVE De- fi points over time? Stopping metformin of- (P = 0.010) risk reduction for myocardial spite these proven bene ts, metformin ten results in poorly controlled glycemia infarction and a 36% reduction for total remains contraindicated in a large seg- and/or the need for other agents with their mortality (P = 0.011) compared with con- ment of the type 2 diabetic population, own adverse-effect profiles. -
Treatment Patterns, Persistence and Adherence Rates in Patients with Type 2 Diabetes Mellitus in Japan: a Claims- Based Cohort Study
Open access Research BMJ Open: first published as 10.1136/bmjopen-2018-025806 on 1 March 2019. Downloaded from Treatment patterns, persistence and adherence rates in patients with type 2 diabetes mellitus in Japan: a claims- based cohort study Rimei Nishimura,1 Haruka Kato,2 Koichi Kisanuki,2 Akinori Oh,2 Shinzo Hiroi,2 Yoshie Onishi,3 Florent Guelfucci,4 Yukio Shimasaki2 To cite: Nishimura R, Kato H, ABSTRACT Strengths and limitations of this study Kisanuki K, et al. Treatment Objective To determine real-world trends in antidiabetic patterns, persistence and drug use, and persistence and adherence, in Japanese ► This retrospective evaluation of administrative adherence rates in patients patients with type 2 diabetes mellitus (T2DM). with type 2 diabetes mellitus claims data (2011–2015) using the Japan Medical Design Retrospective evaluation of administrative claims in Japan: a claims-based Data Center (JMDC) and Medical Data Vision (MDV) data (2011–2015) using the Japan Medical Data Center cohort study. BMJ Open databases was conducted to determine real-world (JMDC) and Medical Data Vision (MDV) databases. 2019;9:e025806. doi:10.1136/ trends in antidiabetic drug use, and persistence and Setting Analysis of two administrative claims databases bmjopen-2018-025806 adherence, in Japanese patients with type 2 dia- for Japanese patients with T2DM. betes mellitus (T2DM); 40 908 and 90 421 patients ► Prepublication history and Participants Adults (aged ≥18 years) with an International additional material for this were included from the JMDC and MDV databases, Classification of Diseases, 10th Revision code of T2DM and paper are available online. To respectively. at least one antidiabetic drug prescription. -
The Na+/Glucose Co-Transporter Inhibitor Canagliflozin Activates AMP-Activated Protein Kinase by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels
Page 1 of 37 Diabetes Hawley et al Canagliflozin activates AMPK 1 The Na+/glucose co-transporter inhibitor canagliflozin activates AMP-activated protein kinase by inhibiting mitochondrial function and increasing cellular AMP levels Simon A. Hawley1†, Rebecca J. Ford2†, Brennan K. Smith2, Graeme J. Gowans1, Sarah J. Mancini3, Ryan D. Pitt2, Emily A. Day2, Ian P. Salt3, Gregory R. Steinberg2†† and D. Grahame Hardie1†† 1Division of Cell Signalling & Immunology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK 2Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada 3Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, Scotland, UK Running title: Canagliflozin activates AMPK Corresponding authors: Dr. D. G. Hardie, Division of Cell Signalling & Immunology, School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK; Dr. G.R. Steinberg, Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada Tel: +44 (1382) 384253; FAX: +44 (1382) 385507; e-mail: [email protected] Tel: +1 (905) 525-9140 ext.21691; email: [email protected] Word count in main text: 3,996 Number of Figures: 7 †these authors made equal contributions to this study ††joint corresponding authors Diabetes Publish Ahead of Print, published online July 5, 2016 Diabetes Page 2 of 37 Hawley et al Canagliflozin activates AMPK 2 ABSTRACT Canagliflozin, dapagliflozin and empagliflozin, all recently approved for treatment of Type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose re- uptake by SGLT2 in the kidney, without affecting intestinal glucose uptake by SGLT1. -
Valsartan in Combination with Metformin and Gliclazide in Diabetic
Patra et al. Future Journal of Pharmaceutical Sciences (2021) 7:157 Future Journal of https://doi.org/10.1186/s43094-021-00307-2 Pharmaceutical Sciences RESEARCH Open Access Valsartan in combination with metformin and gliclazide in diabetic rat model using developed RP-HPLC method Rasmita Patra, Yedukondalu Kollati, Sampath Kumar NS and Vijaya R. Dirisala* Abstract Background: Oral administration of biguanides (metformin) and sulfonylureas (gliclazide) are the most common approach of management of type 2 diabetes in humans. Among these diabetic patients, approximately 40–60% suffers from hypertension. Hence, the need of the day is application of polytherapy. A major challenge in polytherapy is the drug-drug interactions that may arise. Hence, this study is focused to develop a reverse phase high-performance liquid chromatography (RP-HPLC) method for concurrent estimation of diabetic drug metformin and hypertension drug valsartan using C18 column and find any possible pharmacokinetic interactions between the two drug combinations strategies, i.e., metformin-valsartan and gliclazide-valsartan in streptozotocin-induced diabetic rats. Result: The bioanalysis of drug-drug interaction pharmacokinetic result showed no significant difference in the tmax of single treatment of gliclazide and single treatment of metformin or upon co-administration with valsartan. Conclusion: Our study has shown that polytherapy of valsartan, a drug administered for hypertension along with hypoglycemic drugs metformin and gliclazide, can be advantageous and safe in patients suffering from both diabetes and hypertension. Keywords: RP-HPLC, Metformin, Valsartan, Gliclazide, Hypertension, Diabetes mellitus Background disease if left undetected or untreated. Such patients re- Diabetes has become a growing epidemic, and the per- quire polytherapy wherein drug-drug interactions may centage of patient population is increasing in leaps and lead to adverse side effects [5, 6]. -
Effect of Oral Hypoglycaemic Agents on Glucose Tolerance in Pancreatic Diabetes
Gut: first published as 10.1136/gut.13.4.285 on 1 April 1972. Downloaded from Gut, 1972, 13, 285-288 Effect of oral hypoglycaemic agents on glucose tolerance in pancreatic diabetes B. I. JOFFE, W. P. U. JACKSON, S. BANK, AND A. I. VINIK From the Department of Medicine, Witwatersrand University Medical School, Johannesburg, the Gastro- intestinal and Endocrine Research Units of Cape Town University Medical School, and the Chemical Pathology Department of Natal University, South Africa SUMMARY The short-term therapeutic effect of oral hypoglycaemic agents has been assessed in 12 patients with symptomatic diabetes secondary to chronic pancreatitis (pancreatic diabetes). In six patients who had moderate to severe carbohydrate intolerance, associated with severe insulino- paenia during arginine infusion, the potent sulphonylurea chlorpropamide produced no change in the fasting blood glucose level after two weeks of treatment. This contrasted with the significant reduction produced in a matched group of maturity-onset primary diabetics. The six patients with milder diabetes, and a greater (although still subnormal) insulin secretory capacity, showed an improvement in oral glucose tolerance during the first hour following glucose administration while on chlorpropamide. When the biguanide phenformin was substituted for chlorpropamide in five of these patients, a statistically insignificant improvement in glucose tolerance was observed during treatment. Applications of these findings to the practical management of pancreatic diabetes are briefly http://gut.bmj.com/ considered. Chronic pancreatitis is frequently complicated by and two women, ranging from 30 to 67 years of age. diabetes (pancreatic diabetes). Recent studies The diagnosis of pancreatitis was confirmed on the utilizing immunoassay procedures (Joffe, Bank, basis of a gross abnormality in at least two aspects of Jackson, Keller, O'Reilly, and Vinik, 1968; Anderson the pancreatic function test, namely, a low volume of on September 24, 2021 by guest. -
Dipeptidyl Peptidase-4 Inhibitors and Combinations
Dipeptidyl Peptidase-4 Inhibitors & Combinations Policy Number: C5169A CRITERIA EFFECTIVE DATES: ORIGINAL EFFECTIVE DATE LAST REVIEWED DATE NEXT REVIEW DATE 06/2016 10/30/2019 10/30/2020 J CODE TYPE OF CRITERIA LAST P&T APPROVAL/VERSION NA RxPA Q4 2019 20191030C5169-A PRODUCTS AFFECTED: KAZANO (alogliptin/metformin), KOMBIGLYZE XR (saxagliptin/metformin extended-release), NESINA (alogliptin), ONGLYZA (saxagliptin), OSENI (alogliptin/pioglitazone), JANUMET (sitagliptin/metformin), JANUMET XR (sitagliptin/metformin extended-release), JANUVIA (sitagliptin), JENTADUETO (linagliptin/metformin), JENTADUETO XR (linagliptin/metformin extended-release), KAZANO (alogliptin/metformin), KOMBIGLYZE XR (saxagliptin/metformin extended-release), NESINA (alogliptin), ONGLYZA (saxagliptin), OSENI (alogliptin/pioglitazone) TRADJENTA (linagliptin), JANUVIA (sitagliptin) DRUG CLASS: Dipeptidyl Peptidase-4 Inhibitor-(Biguanide Combinations), DPP-4 Inhibitor- Thiazolidinedione Combinations ROUTE OF ADMINISTRATION: Oral PLACE OF SERVICE: Retail Pharmacy AVAILABLE DOSAGE FORMS: Alogliptin Benzoate TABS 12.5MG,Alogliptin Benzoate TABS 25MG, Alogliptin Benzoate TABS 6.25MG, Alogliptin-Metformin HCl TABS 12.5-1000MG Alogliptin-Metformin HCl TABS 12.5-500MG, Janumet TABS 50-1000MG, Janumet TABS 50- 500MG, Janumet XR TB24 100-1000MG, Janumet XR TB24 50-1000MG, Janumet XR TB24 50- 500MG, Januvia TABS 100MG, Januvia TABS 25MG, Januvia TABS 50MG, Jentadueto TABS 2.5- 1000MG, Jentadueto TABS 2.5-500MG, Jentadueto TABS 2.5-500MG, Jentadueto TABS 2.5- 850MG, Jentadueto -
Polyhexamethylene Biguanide Hydrochloride) As Used in Cosmetics
Safety Assessment of Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride) as Used in Cosmetics Status: Tentative Report for Public Comment Release Date: September 26, 2017 Panel Date: December 4-5, 2017 All interested persons are provided 60 days from the above date to comment on this safety assessment and to identify additional published data that should be included or provide unpublished data which can be made public and included. Information may be submitted without identifying the source or the trade name of the cosmetic product containing the ingredient. All unpublished data submitted to CIR will be discussed in open meetings, will be available at the CIR office for review by any interested party and may be cited in a peer-reviewed scientific journal. Please submit data, comments, or requests to the CIR Executive Director, Dr. Bart Heldreth. The 2017 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Executive Director is Bart Heldreth, Ph.D. This report was prepared by Wilbur Johnson, Jr., M.S., Senior Scientific Analyst and Ivan Boyer, Ph.D., former Senior Toxicologist. © Cosmetic Ingredient Review 1620 L STREET, NW, SUITE 1200 ◊ WASHINGTON, DC 20036-4702 ◊ PH 202.331.0651 ◊ FAX 202.331.0088 ◊ [email protected] ABSTRACT: The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the safety of Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride), which functions as a preservative in cosmetic products. -
Objectives Anti-Hyperglycemic Therapeutics
9/22/2015 Some Newer Non-Insulin Therapies for Type 2 Diabetes:Present and future Faculty/presenter disclosure Speaker’s name: Dr. Robert G. Josse SGLT2 Inhibitors Grants/research support: Astra Zeneca, BMS, Boehringer Dopamine D2 Receptor Agonist Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Roche, Bile acid sequestrant sanofi, Consulting Fees: Astra Zeneca, BMS, Eli Lilly, Janssen, Merck, Dr Robert G Josse Division of Endocrinology & Metabolism Speakers bureau: Janssen, Astra Zeneca, BMS, Merck, St. Michael’s Hospital Professor of Medicine Stocks and Shares:None University of Toronto 100-year History of Objectives Anti-hyperglycemic Therapeutics 14 Discuss the mechanism of action of SGLT2 inhibitors, SGLT-2 inhibitor 12 Bromocriptine-QR dopamine D2 receptor agonists and bile acid sequestrants Bile acid sequestrant in the management of type 2 diabetes Number of 10 DPP-4 inhibitor classes of GLP-1 receptor agonist Amylinomimetic anti- 8 Glinide Basal insulin analogue Identify the benefits and risks of the newer non-insulin hyperglycemic Thiazolidinedione agents 6 Alpha-glucosidase inhibitor treatment options Phenformin Human Rapid-acting insulin analogue 4 Sulphonylurea insulin Metformin Intermediate-acting insulin Phenformin Describe the potential uses of these therapies in the 2 withdrawn Soluble insulin treatment of type 2 diabetes 0 1920 1940 1960 1980 2000 2020 Year UGDP, DCCT and UKPDS studies. Buse, JB © 1 9/22/2015 Renal handling of glucose Collecting (180 L/day) Glomerulus duct (1000 mg/L) Proximal =180 g/day Distal tubule S1 tubule Glucose ~90% filtration SGLT2 Inhibitors ~10% S3 Glucose reabsorption Loop No/minimal of Henle glucose excretion S1 segment of proximal tubule S3 segment of proximal tubule - ~90% glucose reabsorbed - ~10% glucose reabsorbed - Facilitated by SGLT2 - Facilitated by SGLT1 SGLT = Sodium-dependent glucose transporter Adapted from: 1. -
A Review on Evolution in Triglyceride Determination
Available online at www.derpharmachemica.com ISSN 0975-413X Der Pharma Chemica, 2018, 10(5): 84-88 CODEN (USA): PCHHAX (http://www.derpharmachemica.com/archive.html) Sodium-glucose co-transporter 2 (SGLT2) Inhibitors: New Target for Type 2 Diabetes Mellitus (T2DM) Review Swapna Vadlamani* Asst. proffesor, NIPER, Hyderabad, Andhra Pradesh, India ABSTRACT Introduction: Knocking out type2 diabetes by new insulin independent renal glucose transporters as targets, reducing the side effects related to high rise in glucose levels is a more efficient way to manage diabetes. Sodium-glucose co-transporter 2 (SGLT2) inhibitors block reabsorption of glucose back into the blood and stimulate secretion in urine in a way controlling blood glucose levels. Areas discussed: We emphasize in this review an overview of type 2 diabetes. New insulin independent targets, SGLT family inhibitors and their mechanism of action are briefly discussed. Molecular modeling studies carried out for new analogues of SGLT2 were indicated and also about current marketed SGLT drugs their safety issues are briefly outlined. Conclusion: SGLT2 inhibitors are very promising drugs for near future, where insulin sensitization is a problem. A combination of drugs related to insulin dependent pathway and also independent pathway like SGLT2/SGLT1 drugs will be more effective in glycemic control with lesser side effects. Keywords: Type II Diabetes, SGLT2 inhibitors INTRODUCTION Present scenario of food habits and absolutely very less physical activity is becoming the major cause for obesity finally leading to diabetes. Diabetes is said to be a rich man disease and mostly occurs at the later age of 40, but now one in every 5 persons at early age diagnosed turned to be diabetic mainly because of lifestyle changes. -
Type 2 Diabetes Treatment Recommendations Update
abetes & Di M f e o t a l b a o Cornell, J Diabetes Metab 2014, 5:8 n l r i s u m o DOI: 10.4172/2155-6156.1000414 J Journal of Diabetes and Metabolism ISSN: 2155-6156 Review Article Open Access Type 2 Diabetes Treatment Recommendations Update: Appropriate Use of Dipeptidyl Peptidase-4 Inhibitors Susan Cornell* Midwestern University, Chicago College of Pharmacy, Downers Grove, IL, USA Abstract In this article, recommendations from the 2012 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) position statement are discussed with an emphasis on the appropriate use of Dipeptidyl Peptidase-4 (DPP-4) inhibitors in individuals with Type 2 Diabetes Mellitus (T2DM). The 2012 ADA/EASD position statement emphasizes individualization of treatment, with glycated hemoglobin (A1C) targets being determined for each patient based on life expectancy, complications, disease duration, comorbidities, such as cardiovascular disease or cognitive impairment, and the risk of hypoglycemia and other adverse events. Patients’ attitudes and support systems should also be considered. Recommendations for pharmacotherapy are less prescriptive and should be based on a patient’s needs, preferences, and tolerances. In general, metformin is recommended as first- line therapy for most patients, although combination of 2 noninsulin agents or insulin alone should be considered in patients with baseline A1C ≥ 9.0%. Add-on therapy to metformin will likely be needed to achieve and maintain glycemic control as the disease progresses. It is important to avoid therapies that increase the risk of weight gain or and, especially in older patients, hypoglycemia. As discussed in this review, DPP-4 inhibitors are well tolerated and effectively lower A1C and improve β-cell function without increasing the risk of hypoglycemia and weight gain. -
Assessing the Value of Treatment For
Tim Wilsdon ASSESSING THE VALUE OF Lilian Li TREATMENT FOR DIABETES TO PATIENTS, THE HEALTHCARE SYSTEM, AND WIDER SOCIETY – A CASE STUDY ON CHINA TABLE OF CONTENTS EXECUTIVE SUMMARY .................................................................................................................................... 4 1. INTRODUCTION ................................................................................................................................... 11 1.1. Background ............................................................................................................................12 1.2. Our approach .........................................................................................................................13 1.3. The structure of the report .....................................................................................................13 2. DIABETES ............................................................................................................................................. 14 2.1. Access to medicines for diabetes..........................................................................................20 2.2. The value of treatment for diabetes .......................................................................................25 2.3. The value of medicines for diabetes in HICs and MICs .........................................................31 3. POLICY IMPLICATIONS ..................................................................................................................... -
Phenformin Hydrochloride
456 Antidiabetics 4. Levien TL, et al. Nateglinide therapy for type 2 diabetes melli- 2. Wolffenbuttel BHR, Huijberts MSP. Aminoguanidine, a poten- ing then treatment with pioglitazone should be stopped; treat- tus. Ann Pharmacother 2001; 35: 1426–34. tial drug for the treatment of diabetic complications. Neth J Med ment should also be stopped if jaundice develops. 1993; 42: 205–8. 5. Fonseca V. et al. Addition of nateglinide to rosiglitazone mono- 1. Maeda K. Hepatocellular injury in a patient receiving pioglita- therapy suppresses mealtime hyperglycemia and improves over- 3. Abdel-Rahman E, Bolton WK. Pimagedine: a novel therapy for zone. Ann Intern Med 2001; 135: 306. all glycemic control. Diabetes Care 2003; 26: 1685–90. diabetic nephropathy. Expert Opin Invest Drugs 2002; 11: 2. May LD, et al. Mixed hepatocellular-cholestatic liver injury af- 6. Campbell IW. Nateglinide—current and future role in the treat- 565–74. ter pioglitazone therapy. Ann Intern Med 2002; 136: 449–52. ment of patients with type 2 diabetes mellitus. Int J Clin Pract 4. Thornalley PJ. Use of aminoguanidine (pimagedine) to prevent 3. Pinto AG, et al. Severe but reversible cholestatic liver injury af- 2005; 59: 1218–28. the formation of advanced glycation endproducts. Arch Biochem ter pioglitazone therapy. Ann Intern Med 2002; 137: 857. Biophys 2003; 419: 31–40. 4. Chase MP, Yarze JC. Pioglitazone-associated fulminant hepatic Preparations failure. Am J Gastroenterol 2002; 97: 502–3. Proprietary Preparations (details are given in Part 3) 5. Farley-Hills E, et al. Fatal liver failure associated with pioglita- Arg.: Nateglin; Starlix; Braz.: Starlix; Canad.: Starlix; Chile: Gluconol; Star- zone.