Essay Example on Pharmacological Management and Interventions in the Prevention of type 2 Diabetes









Mellitus Currently accepted interventions can be divided into 2 levels LEVEL 1 Lifestyle modification with diet and exercise see other group contribution LEVEL 2 Lifestyle modification Medication or surgical intervention Progression to level 2 interventions have been supported by clinical trials Prevention 2015 Ramachandran et al 2006 Defronzo et al 2010 GR et al 2008 and are applicable when level 1 interventions have failed to reach the intended goal or when participation in intensive lifestyle intervention programs is impossible These interventions should be particularly considered in cases of combined IFG IGT Management of preventing diabetes should aim at Delaying or preventing the onset of diabetes Preserving beta cell function Preventing or delaying microvascular and macrovascular complications Pharmacological therapy can improve insulin sensitivity preserve beta cell function promote weight loss and delay CHO metabolism Smith Marsh 2013 Yet should a lifestyle condition be managed with lifelong medication Medication could influence patient and doctor indicating no need for further lifestyle modification 

Medication used needs to be safe and effective with a low side effect profile in long term use Gillies et al 2007 CDC estimates 79 000000 prediabetics in USA of which only 40 50 will progress to T2DM during their lifetime DeFronzo and Abdul Ghani 2011 This could mean a large number of unnecessarily treated patients This will result in a significant financial burden and cost effectiveness needs to be considered ADA guidelines 2018 recommend Metformin use where lifestyle modification has failed or in high risk patients Metformin is recommended due to its long term safety record American Diabetes Association 2018 NICE recommends Metformin to support lifestyle changes where HBA1c or FBG has deteriorated despite an intensive lifestyle program or inability to participate in a program HCPs should continue offering advice on diet and physical activity NICE supports introduction of Orlistat where the BMI is 28 with review after 12 weeks and discontinuation if weight loss 5 body weight AACE ACE guidelines recommend use of medication if lifestyle fails to produce improvement after 6 months and for high risk patients Recommended as initial weight loss medications for prediabetes are phentermine orlistat lorcaserin phentermine topiramate ER naltrexone bupropion liraglutide and to consider antihyperglycemic medication 

Recommended are Acarbose and Metformin as both have a 25 30 risk reduction are well tolerated and safe If normoglycaemia is not achieved introduction of thiazolidinediones TZD and GLP1agonists is advocated with caution TZD s can reduce risk by 60 75 but their use is associated with side effects of subcutaneous fat gain water retention heart failure and an increased fracture risk Due to its side effects rosiglitazone is no longer commercially available GLP1 agonist Liraglutide plus lifestyle management showed a potential benefit in weight management in the SCALE study when compared to placebo in non diabetic patients with increased BMI It took 2 7 times longer than placebo for patients to develop diabetes NNT to normoglycaemia was 3 le Roux et al 2017 Drug Mechanism of action Clinical Trials Results Side effects Biguanides Metformin Suppression of Hepatic gluconeogenesis by stimulating AMPK pathway in liver and improve activation of CLOCK genes in some peripheral tissues DPP 2 8 years 31 reduction 10 years 18 Megaloblastic anaemia in longterm therapy dose dependent Metformin induces Vitamin B12 malabsorption Indian Diabetes IDPP 1 Study 25 reduction Lactic Acidosis discontinue if eGF 30ml min Meta analysis 31 RCT 40 reduction GLINT Alpha glucosidase Ascarbose Slows CHO absorption and decreases

 Post Prandial hyperglycaemia decreasing workload of pancreas Stop NIDDM 3 3 years 35 8 reduction Also showed reduction MI 91 and new onset hypertension flatulence and diarrhoea TZDs Pioglitazone ACTNOW piogliazone 3 75 years reduced risk conversion by 72 Weight gain oedema Increased fracture risk Rosiglitazone Withdrawn from market DREAM Rosiglit rampril 60 reduction CCF Oedema CANOE low dose Rosiglit metformin 3 9 years 66 reduction Low incidence adverse events Lipase inhibitors Orlistat Xenical Slow intestinal fat absorption XENDOS Xenical Prevention of Diabetes in Obese Subjects 4 years 37 3 decrease risk compared lifestyle changes alone and greater weight loss 5 8 Kg Torgerson et al 2004 Sjöström et al 2004 Phentermine topiramate 71 79 2 years Garvey et al 2014 Basal Insulin Glargine ORIGIN DPPOS 31 56 reduction diabetes incidence DPP 4 Inhibitor Vildagliptin 12 week Double blind 32 reduction PPG GLP1agonists Exenatide Liraglutide Animal models 12 week restoration of islet cell structure and reversal of IFG or IGT SCALE Obesity and prediabetes trial 2017 Liraglutide 3 years 80 reduction diabetes posthoc 66 le Roux et al 2017 SAEs reported 15 similar to placebo group 13 increased numbers of gallbladder and pancreatitis related events Breast neoplasms and increased heart rate Table adapted from Portero McLellan et al 2014 Table adapted from Portero McLellan et al 2014 More recently bariatric surgery has been proposed to morbidly obese patients BMI 35kg m3 with prediabetes after failure of lifestyle interventions yielding good results regarding weight loss and return to normoglycemia However due to the high morbidity of the procedure each case should be assessed on its merits and the procedures should not be recommended for the management of prediabetes alone

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