CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM--2016 EXECUTIVE SUMMARY.

Abbreviations: A1C = hemoglobin A1C AACE = American Association of Clinical Endocrinologists ACCORD = Action to Control Cardiovascular Risk in Diabetes ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure ACEI = angiotensinconverting enzyme inhibitor AGI = alpha-glucosidase inhibitor apo B = apolipoprotein B ARB = angiotensin II receptor blocker ASCVD = atherosclerotic cardiovascular disease BAS = bile acid sequestrant BMI = body mass index BP = blood pressure CHD = coronary heart disease CKD = chronic kidney disease CVD = cardiovascular disease DKA = diabetic ketoacidosis DPP-4 = dipeptidyl peptidase 4 EPA = eicosapentaenoic acid FDA = Food and Drug Administration GLP-1 = glucagon-like peptide 1 HDL-C = high-density-lipoprotein cholesterol LDL-C = low-densitylipoprotein cholesterol LDL-P = low-density-lipoprotein particle Look AHEAD = Look Action for Health in Diabetes NPH = neutral protamine Hagedorn OSA = obstructive sleep apnea SFU = sulfonylurea SGLT-2 = sodium glucose cotrans...

[1]  Will G. Hopkins,et al.  Effects of Different Modes of Exercise Training on Glucose Control and Risk Factors for Complications in Type 2 Diabetic Patients: a Meta-Analysis , 2007, Diabetes Care.

[2]  N. Weissman,et al.  A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. , 2011, The Journal of clinical endocrinology and metabolism.

[3]  R. Rubin,et al.  Patient reported outcomes in adults with type 2 diabetes on basal insulin randomized to addition of mealtime pramlintide or rapid-acting insulin analogs , 2010, Current medical research and opinion.

[4]  Susan Redline,et al.  Association of usual sleep duration with hypertension: the Sleep Heart Health Study. , 2006, Sleep.

[5]  D. Tanné,et al.  Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. , 2016, The New England journal of medicine.

[6]  B. Hutton,et al.  Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials. , 2004, The American journal of clinical nutrition.

[7]  S. Yusuf,et al.  n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. , 2012, The New England journal of medicine.

[8]  L. Carlson,et al.  Nicotinic acid: the broad‐spectrum lipid drug. A 50th anniversary review , 2005, Journal of internal medicine.

[9]  P. Cryer.  Death during intensive glycemic therapy of diabetes: mechanisms and implications. , 2011, The American journal of medicine.

[10]  J. Leahy,et al.  Introducing a simplified approach to insulin therapy in type 2 diabetes: a comparison of two single‐dose regimens of insulin glulisine plus insulin glargine and oral antidiabetic drugs , 2008, Diabetes, obesity & metabolism.

[11]  J. Rosenstock,et al.  Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes , 2010, Diabetes, obesity & metabolism.

[12]  Erland Erdmann,et al.  Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial , 2005, The Lancet.

[13]  F. Greenway,et al.  Effects of Naltrexone Sustained- Release/Bupropion Sustained-Release Combination Therapy on Body Weight and Glycemic Parameters in Overweight and Obese Patients With Type 2 Diabetes , 2013, Diabetes Care.

[14]  G. Bray,et al.  Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. , 2001, The New England journal of medicine.

[15]  R. Collins,et al.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010, The Lancet.

[16]  M. Hanefeld,et al.  Association of sulphonylurea treatment with all-cause and cardiovascular mortality: A systematic review and meta-analysis of observational studies , 2013, Diabetes & vascular disease research.

[17]  B. Ahrén.  Clinical results of treating type 2 diabetic patients with sitagliptin, vildagliptin or saxagliptin--diabetes control and potential adverse events. , 2009, Best practice & research. Clinical endocrinology & metabolism.

[18]  M. Nieminen,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[19]  M. Perri,et al.  Effects of four maintenance programs on the long-term management of obesity. , 1988, Journal of consulting and clinical psychology.

[20]  S. Yusuf,et al.  Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial , 2008, The Lancet.

[21]  Indra Ramasamy,et al.  Recent advances in physiological lipoprotein metabolism , 2014, Clinical chemistry and laboratory medicine.

[22]  M. Hanefeld,et al.  Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. , 2004, European heart journal.

[23]  I. Hirsch,et al.  Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium–Glucose Cotransporter 2 Inhibition , 2015, Diabetes Care.

[24]  J. Isaacsohn,et al.  Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects. , 1999, Archives of internal medicine.

[25]  Grant D. Huang,et al.  Glucose control and vascular complications in veterans with type 2 diabetes. , 2009, The New England journal of medicine.

[26]  Giovanni Corrao,et al.  A meta-analysis of alcohol consumption and the risk of 15 diseases. , 2004, Preventive medicine.

[27]  M. Charles,et al.  Niacin treatment of the atherogenic lipid profile and Lp(a) in diabetes , 2002, Diabetes, obesity & metabolism.

[28]  A. Powell.  Two-year sustained weight loss and metabolic benefits with controlled-release Phentermine/Topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study , 2012 .

[29]  S. Fowler,et al.  Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. , 2005, Diabetes care.

[30]  Christopher P Cannon,et al.  Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. , 2006, Journal of the American College of Cardiology.

[31]  P. Renshaw,et al.  [Detection, evaluation, and treatment of high blood cholesterol in adults]. , 2001, Revista panamericana de salud publica = Pan American journal of public health.

[32]  H. Kuipers,et al.  Influence of acute exercise on hyperglycemia in insulin-treated type 2 diabetes. , 2006, Medicine and science in sports and exercise.

[33]  A. Vinik.  The approach to the management of the patient with neuropathic pain. , 2010, The Journal of clinical endocrinology and metabolism.

[34]  David M Nathan,et al.  10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. , 2009, Lancet.

[35]  G. Bakris,et al.  Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. , 2008, The New England journal of medicine.

[36]  Brenda R. Hemmelgarn,et al.  Notice , 2012, Kidney International Supplements.

[37]  John B Buse,et al.  Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. , 2016, The New England journal of medicine.

[38]  A. Vaag,et al.  Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial , 2009, Diabetologia.

[39]  R Peto,et al.  Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. , 2008, Lancet.

[40]  A. Astrup,et al.  Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide , 2011, International Journal of Obesity.

[41]  B. Zinman,et al.  Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes , 2017, The New England journal of medicine.

[42]  S. Studenski,et al.  Relationship Between Vitamin B12 and Sensory and Motor Peripheral Nerve Function in Older Adults , 2012, Journal of the American Geriatrics Society.

[43]  S. Yusuf,et al.  Obesity and the risk of myocardial infarction in 27 000 participants from 52 countries: a case-control study , 2005, The Lancet.

[44]  Ralph A. DeFronzo,et al.  From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus , 2009, Diabetes.

[45]  M. Massi-Benedetti,et al.  Meta‐analysis of individual patient data to assess the risk of hypoglycaemia in people with type 2 diabetes using NPH insulin or insulin glargine , 2010, Diabetes, obesity and metabolism.

[46]  S. Gough,et al.  Low-Volume Insulin Degludec 200 Units/mL Once Daily Improves Glycemic Control Similarly to Insulin Glargine With a Low Risk of Hypoglycemia in Insulin-Naïve Patients With Type 2 Diabetes , 2013, Diabetes Care.

[47]  J. Leahy.  Insulin therapy in type 2 diabetes mellitus. , 2012, Endocrinology and metabolism clinics of North America.

[48]  M. Gnant,et al.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010 .

[49]  Deepak L. Bhatt,et al.  Heart Failure, Saxagliptin, and Diabetes Mellitus: Observations from the SAVOR-TIMI 53 Randomized Trial , 2014, Circulation.

[50]  M. Laakso,et al.  Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial , 2006, The Lancet.

[51]  M. Hanefeld,et al.  Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial , 2009, The Lancet.

[52]  A. Sniderman.  Differential response of cholesterol and particle measures of atherogenic lipoproteins to LDL-lowering therapy: implications for clinical practice. , 2008, Journal of clinical lipidology.

[53]  G. Hovingh,et al.  PCSK9 inhibitors: Novel therapeutic agents for the treatment of hypercholesterolemia. , 2015, European journal of pharmacology.

[54]  J. Roitman,et al.  ACSM's Resource Manual for Guidelines for Exercise Testing and Prescription , 1998 .

[55]  K. Mahaffey,et al.  Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes , 2017, The New England journal of medicine.

[56]  Neil M. Johannsen,et al.  Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. , 2010, JAMA.

[57]  Craig I Coleman,et al.  Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. , 2010, JAMA.

[58]  Michael E. Miller,et al.  The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study , 2010, BMJ : British Medical Journal.

[59]  R. DeFronzo.  Bromocriptine: A Sympatholytic, D2-Dopamine Agonist for the Treatment of Type 2 Diabetes , 2011, Diabetes Care.

[60]  L. Wilkins.  Effect of Bromocriptine‐QR (a Quick‐Release Formulation of Bromocriptine Mesylate) on Major Adverse Cardiovascular Events in Type 2 Diabetes Subjects , 2015, Journal of the American Heart Association.

[61]  J. Mckenney,et al.  National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) , 2002 .

[62]  R. Manders,et al.  Low-intensity exercise reduces the prevalence of hyperglycemia in type 2 diabetes. , 2010, Medicine and science in sports and exercise.

[63]  Z. Bloomgarden.  Sodium glucose transporter 2 inhibition: A new approach to diabetes treatment (抑制钠葡萄糖转运体2：一种新的糖尿病治疗方法) , 2013, Journal of diabetes.

[64]  M. Fischereder,et al.  Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. , 2016, The New England journal of medicine.

[65]  E. Salpeter,et al.  Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. , 2003, The Cochrane database of systematic reviews.

[66]  Jennifer G. Robinson,et al.  Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. , 2015, The New England journal of medicine.

[67]  C. Lamendola,et al.  Benefits of Liraglutide Treatment in Overweight and Obese Older Individuals With Prediabetes , 2013, Diabetes Care.

[68]  Orton,et al.  EFFECTS ON BLOOD PRESSURE OF REDUCED DIETARY SODIUM AND THE DIETARY APPROACHES TO STOP HYPERTENSION ( DASH ) DIET , 2000 .

[69]  R. Bergenstal,et al.  Adjust to Target in Type 2 Diabetes , 2008, Diabetes Care.

[70]  S. Schinner,et al.  Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes , 2009 .

[71]  C. Deacon,et al.  Dipeptidyl peptidase‐4 inhibitors in the treatment of type 2 diabetes: a comparative review , 2011, Diabetes, obesity & metabolism.

[72]  Michael E. Miller,et al.  Effects of intensive glucose lowering in type 2 diabetes. , 2008, The New England journal of medicine.

[73]  R. Meeusen,et al.  Continuous low- to moderate-intensity exercise training is as effective as moderate- to high-intensity exercise training at lowering blood HbA1c in obese type 2 diabetes patients , 2009, Diabetologia.

[74]  A. Cincotta,et al.  Effect of Bromocriptine-QR (a Quick-Release Formulation of Bromocriptine Mesylate) on Major Adverse Cardiovascular Events in Type 2 Diabetes Subjects , 2012, Journal of the American Heart Association.

[75]  L. Niskanen,et al.  Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus. , 1992, The New England journal of medicine.

[76]  C. Deacon,et al.  Glycaemic efficacy of glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors as add‐on therapy to metformin in subjects with type 2 diabetes—a review and meta analysis , 2012, Diabetes, obesity & metabolism.

[77]  Devjit Tripathy,et al.  Pioglitazone for diabetes prevention in impaired glucose tolerance. , 2011, The New England journal of medicine.

[78]  D. Goff,et al.  Impact of intensive glycemic control on the incidence of atrial fibrillation and associated cardiovascular outcomes in patients with type 2 diabetes mellitus (from the Action to Control Cardiovascular Risk in Diabetes Study). , 2014, The American journal of cardiology.

[79]  A. Astrup,et al.  A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. , 2015, The New England journal of medicine.

[80]  Wendy Macdonald,et al.  Identifying Psychosocial Interventions That Improve Both Physical and Mental Health in Patients With Diabetes , 2010, Diabetes Care.

[81]  A. Vinik,et al.  Falls risk in older adults with type 2 diabetes. , 2015, Clinics in geriatric medicine.

[82]  L. Kennedy.  A 26-Week, Randomized, Parallel, Treat-to-Target Trial Comparing Insulin Detemir With NPH Insulin as Add-On Therapy to Oral Glucose-Lowering Drugs in Insulin-Naïve People With Type 2 Diabetes , 2007 .

[83]  S. Haffner,et al.  Adherence to the DASH Diet Is Inversely Associated With Incidence of Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study , 2009, Diabetes Care.

[84]  Atul Malhotra,et al.  A prospective study of sleep duration and coronary heart disease in women. , 2003, Archives of internal medicine.

[85]  S. Cummings,et al.  Thiazolidinedione use and bone loss in older diabetic adults. , 2006, The Journal of clinical endocrinology and metabolism.

[86]  G. Bray,et al.  Medical Therapy for the Patient With Obesity , 2012, Circulation.

[87]  K. Freedland,et al.  The prevalence of comorbid depression in adults with diabetes: a meta-analysis. , 2001, Diabetes care.

[88]  T. Gislason,et al.  Role of snoring and daytime sleepiness in occupational accidents. , 2001, American journal of respiratory and critical care medicine.

[89]  M. Clearfield.  Combination Lipid Therapy in Type 2 Diabetes , 2011, Current atherosclerosis reports.

[90]  Lawrence A Leiter,et al.  Intensive and Standard Blood Pressure Targets in Patients With Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis. , 2012, Archives of internal medicine.

[91]  B. Davis,et al.  Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs a diuretic: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). , 2005, Archives of internal medicine.

[92]  Michael E. Miller,et al.  Long-Term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes , 2011 .

[93]  J. Borén,et al.  Review the Polygenic Nature of Hypertriglyceridaemia: Implications for Defi Nition, Diagnosis, and Management , 2022 .

[94]  Kenneth L. Jones,et al.  Medical writer , 2019, Combatting Burnout.

[95]  S. Yamashita,et al.  Ezetimibe improves postprandial hyperlipidaemia in patients with type IIb hyperlipidaemia , 2009, European journal of clinical investigation.

[96]  Craig Wilson,et al.  Alogliptin after acute coronary syndrome in patients with type 2 diabetes. , 2013, The New England journal of medicine.

[97]  R. DeFronzo,et al.  AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON THE ASSOCIATION OF SGLT-2 INHIBITORS AND DIABETIC KETOACIDOSIS. , 2016, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[98]  E. Bruckert,et al.  Mild to Moderate Muscular Symptoms with High-Dosage Statin Therapy in Hyperlipidemic Patients —The PRIMO Study , 2005, Cardiovascular Drugs and Therapy.

[99]  Robert A. Rizza,et al.  β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes , 2003, Diabetes.

[100]  S. Fowler,et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. , 2002 .

[101]  D. Reda,et al.  Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. , 2015, The New England journal of medicine.

[102]  P. Peduzzi,et al.  Combined angiotensin inhibition for the treatment of diabetic nephropathy. , 2013, The New England journal of medicine.

[103]  Robert A Rizza,et al.  Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. , 2003, Diabetes.

[104]  T. Sbrocco,et al.  Behavioral choice treatment promotes continuing weight loss: preliminary results of a cognitive-behavioral decision-based treatment for obesity. , 1999, Journal of consulting and clinical psychology.

[105]  Ronac Mamtani,et al.  Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes. , 2015, JAMA.

[106]  Mark D. Huffman,et al.  Heart disease and stroke statistics--2013 update: a report from the American Heart Association. , 2013, Circulation.

[107]  R. Henry,et al.  Prevention of Type 2 Diabetes in Subjects With Prediabetes and Metabolic Syndrome Treated With Phentermine and Topiramate Extended Release , 2014, Diabetes Care.

[108]  J. Saver,et al.  Efficacy of fibrates for cardiovascular risk reduction in persons with atherogenic dyslipidemia: a meta-analysis. , 2011, Atherosclerosis.

[109]  B. Charbonnel,et al.  Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin , 2012, Current medical research and opinion.

[110]  Walter T Ambrosius,et al.  Effects of medical therapies on retinopathy progression in type 2 diabetes. , 2010, The New England journal of medicine.

[111]  C. Rosak,et al.  Critical evaluation of the role of acarbose in the treatment of diabetes: patient considerations , 2012, Diabetes, metabolic syndrome and obesity : targets and therapy.

[112]  B. Zinman,et al.  Rosiglitazone-Associated Fractures in Type 2 Diabetes , 2008, Diabetes Care.

[113]  Y. Matsuzawa,et al.  Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). , 2008, Atherosclerosis.

[114]  R. Karas,et al.  The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. , 2013, Journal of the American College of Cardiology.

[115]  S. Fowler,et al.  Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program. , 2005, Diabetes.

[116]  K. Gadde,et al.  Controlled-Release Phentermine/Topiramate in Severely Obese Adults: A Randomized Controlled Trial (EQUIP) , 2011, Obesity.

[117]  J. Whelan,et al.  An evaluation of a television-delivered behavioral weight loss program: are the ratings acceptable? , 1996, Journal of consulting and clinical psychology.

[118]  T. Wilt,et al.  Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. , 1999, The New England journal of medicine.

[119]  S. Redline,et al.  Polysomnographic and health-related quality of life correlates of restless legs syndrome in the Sleep Heart Health Study. , 2009, Sleep.

[120]  R. Loomba,et al.  Efficacy of Colesevelam on Lowering Glycemia and Lipids , 2012, Journal of cardiovascular pharmacology.

[121]  P. O'Neil,et al.  Randomized Placebo‐Controlled Clinical Trial of Lorcaserin for Weight Loss in Type 2 Diabetes Mellitus: The BLOOM‐DM Study , 2012, Obesity.

[122]  C. Rosebraugh,et al.  Weighing risks and benefits of liraglutide--the FDA's review of a new antidiabetic therapy. , 2010, The New England journal of medicine.

[123]  Dennis D. Kim,et al.  A Randomized, Phase 3 Trial of Naltrexone SR/Bupropion SR on Weight and Obesity-related Risk Factors (COR-II) , 2013, Obesity.

[124]  J. Rosenstock,et al.  One-year sustained glycemic control and weight reduction in type 2 diabetes after addition of liraglutide to metformin followed by insulin detemir according to HbA1c target. , 2013, Journal of diabetes and its complications.

[125]  P. Ridker,et al.  Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. , 2014, Journal of the American College of Cardiology.

[126]  John B Buse,et al.  Effects of combination lipid therapy in type 2 diabetes mellitus. , 2010, The New England journal of medicine.

[127]  Y. Handelsman.  Role of Bile Acid Sequestrants in the Treatment of Type 2 Diabetes , 2011, Diabetes Care.

[128]  W. Howard.  Effect of Lowering LDL Cholesterol Substantially Below Currently Recommended Levels in Patients With Coronary Heart Disease and Diabetes: The Treating to New Targets (TNT) study , 2008 .

[129]  C. Rock,et al.  Weight Loss With Naltrexone SR/Bupropion SR Combination Therapy as an Adjunct to Behavior Modification: The COR‐BMOD Trial , 2011, Obesity.

[130]  D. Mikhailidis,et al.  Early Benefit from Structured Care with Atorvastatin in Patients with Coronary Heart Disease and Diabetes Mellitus , 2003, Angiology.

[131]  Jennifer G. Robinson,et al.  Alirocumab as Add-On to Atorvastatin Versus Other Lipid Treatment Strategies: ODYSSEY OPTIONS I Randomized Trial. , 2015, The Journal of clinical endocrinology and metabolism.

[132]  Nish Chaturvedi,et al.  Cardiorenal end points in a trial of aliskiren for type 2 diabetes. , 2012, The New England journal of medicine.

[133]  D. Wile,et al.  Association of Metformin, Elevated Homocysteine, and Methylmalonic Acid Levels and Clinically Worsened Diabetic Peripheral Neuropathy , 2009, Diabetes Care.

[134]  Jackson T. Wright,et al.  2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). , 2014, JAMA.

[135]  O. Chepurny,et al.  Facilitation of β-cell KATP channel sulfonylurea sensitivity by a cAMP analog selective for the cAMP-regulated guanine nucleotide exchange factor Epac , 2010, Islets.

[136]  M. Riddle,et al.  Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes. , 2005, Diabetes care.

[137]  D. Giugliano,et al.  Beneficial effects of a Dietary Approaches to Stop Hypertension eating plan on features of the metabolic syndrome. , 2006, Diabetes care.

[138]  P. Whelton,et al.  Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. , 1997, JAMA.

[139]  I. Hirsch,et al.  Human Insulin for Type 2 Diabetes: An Effective, Less-Expensive Option. , 2017, Journal of the American Medical Association (JAMA).

[140]  M. S. Lewis,et al.  Use of Twice-Daily Exenatide in Basal Insulin–Treated Patients With Type 2 Diabetes , 2011, Annals of Internal Medicine.

[141]  Markolf Hanefeld,et al.  Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. , 2003, JAMA.

[142]  C. Ballantyne,et al.  A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. , 2014, The New England journal of medicine.

[143]  M. Roncaglioni,et al.  n-3 fatty acids in patients with multiple cardiovascular risk factors. , 2013, The New England journal of medicine.

[144]  M. Pfeffer,et al.  Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. , 2004, JAMA.

[145]  Rebecca S. Williamson,et al.  The National Health and Nutrition Examination Survey, 1999–2006 , 2011 .

[146]  S. Kaul,et al.  The cardiovascular safety of diabetes drugs--insights from the rosiglitazone experience. , 2013, The New England journal of medicine.

[147]  V. Woo,et al.  Long-Term Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Receiving High Doses of Insulin , 2012, Annals of Internal Medicine.

[148]  C. Furberg,et al.  Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project). , 2005, The American journal of cardiology.

[149]  H. Rodbard,et al.  American association of clinical endocrinologists' guidelines for management of dyslipidemia and prevention of atherosclerosis. , 2012, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[150]  K. Lipska,et al.  Use of Metformin in the Setting of Mild-to-Moderate Renal Insufficiency , 2011, Diabetes Care.

[151]  H. Rodbard,et al.  American Association of Clinical Endocrinologists' Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis: executive summary. , 2012, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[152]  Rebecca S. Williamson,et al.  Association of biochemical B₁₂ deficiency with metformin therapy and vitamin B₁₂ supplements: the National Health and Nutrition Examination Survey, 1999-2006. , 2012, Diabetes care.

[153]  S. Tunis,et al.  Cost effectiveness of insulin glargine plus oral antidiabetes drugs compared with premixed insulin alone in patients with type 2 diabetes mellitus in Canada , 2010, Applied health economics and health policy.

[154]  Atul Malhotra,et al.  Association between reduced sleep and weight gain in women. , 2006, American journal of epidemiology.

[155]  B. Zinman,et al.  Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. , 2006, The New England journal of medicine.

[156]  J. Rosenstock,et al.  Effects of Exenatide and Lifestyle Modification on Body Weight and Glucose Tolerance in Obese Subjects With and Without Pre-Diabetes , 2010, Diabetes Care.

[157]  M. Nauck.  Update on developments with SGLT2 inhibitors in the management of type 2 diabetes , 2014, Drug design, development and therapy.

[158]  Sarah Parish,et al.  Effects of extended-release niacin with laropiprant in high-risk patients. , 2014, The New England journal of medicine.

[159]  E. Braunwald,et al.  Coronary heart disease Acute coronary syndromes and diabetes : is intensive lipid lowering beneficial ? Results of the PROVE IT-TIMI 22 trial , 2006 .

[160]  J. Chaput,et al.  Inadequate sleep as a contributor to obesity and type 2 diabetes. , 2013, Canadian journal of diabetes.

[161]  C. O'connor,et al.  Randomized Clinical Trial of Quick-Release Bromocriptine Among Patients With Type 2 Diabetes on Overall Safety and Cardiovascular Outcomes , 2010, Diabetes Care.

[162]  R. Plodkowski,et al.  Clinical practice guidelines for healthy eating for the prevention and treatment of metabolic and endocrine diseases in adults: cosponsored by the American Association of Clinical Endocrinologists/the American College of Endocrinology and the Obesity Society: executive summary. , 2013, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[163]  W. Ambrosius,et al.  Epidemiologic Relationships Between A1C and All-Cause Mortality During a Median 3.4-Year Follow-up of Glycemic Treatment in the ACCORD Trial , 2010, Diabetes Care.

[164]  Alison B. Evert,et al.  Nutrition Therapy Recommendations for the Management of Adults With Diabetes , 2013, Diabetes Care.

[165]  G. Dogbey,et al.  Hypoglycemia in Type 2 Diabetes - More Common Than You Think , 2015, Journal of diabetes science and technology.

[166]  R. Horwitz,et al.  Determining triglyceride reductions needed for clinical impact in severe hypertriglyceridemia. , 2014, The American journal of medicine.

[167]  P. Ridker,et al.  Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low-density lipoprotein cholesterol <70 mg/dl and C-reactive protein <2 mg/l: an analysis of the PROVE-IT TIMI-22 trial. , 2005, Journal of the American College of Cardiology.

[168]  A. Keech,et al.  Effects of Fenofibrate Treatment on Cardiovascular Disease Risk in 9,795 Individuals With Type 2 Diabetes and Various Components of the Metabolic Syndrome , 2008, Diabetes Care.

[169]  K. Furie,et al.  Pioglitazone and Risk for Bone Fracture: Safety Data From a Randomized Clinical Trial. , 2016, The Journal of clinical endocrinology and metabolism.

[170]  Shari Bolen,et al.  Systematic Review: Comparative Effectiveness and Safety of Oral Medications for Type 2 Diabetes Mellitus , 2007, Annals of Internal Medicine.

[171]  M. Pencina,et al.  Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. , 2015, The New England journal of medicine.

[172]  Joël Ménard,et al.  Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial , 1998, The Lancet.

[173]  Irl B Hirsch,et al.  American association of clinical endocrinologists and american college of endocrinology - clinical practice guidelines for developing a diabetes mellitus comprehensive care plan - 2015. , 2015, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[174]  Robert A Greevy,et al.  Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes Mellitus , 2012, Annals of Internal Medicine.

[175]  Y. Matsuzawa,et al.  Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis , 2007, The Lancet.

[176]  D. Ryan,et al.  Weight-Loss Therapy in Type 2 Diabetes: Effects of Phentermine and Topiramate Extended Release , 2014, Diabetes Care.

[177]  John H Fuller,et al.  Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial , 2004, The Lancet.

[178]  R. Rosenson,et al.  Colesevelam HCl effects on atherogenic lipoprotein subclasses in subjects with type 2 diabetes. , 2009, Atherosclerosis.

[179]  Jennifer G. Robinson,et al.  Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. , 2015, The New England journal of medicine.

[180]  G. Bray,et al.  Reduction in Weight and Cardiovascular Disease Risk Factors in Individuals With Type 2 Diabetes , 2007, Diabetes Care.

[181]  AndrewJ. S. Coats.  MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial , 2002, The Lancet.

[182]  H. Parving,et al.  Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in patients with type 2 diabetes. , 2001, Diabetes care.

[183]  A. Nicolucci,et al.  Effect of an intensive exercise intervention strategy on modifiable cardiovascular risk factors in subjects with type 2 diabetes mellitus: a randomized controlled trial: the Italian Diabetes and Exercise Study (IDES). , 2010, Archives of internal medicine.

[184]  R B Haynes,et al.  A randomized trial of improved weight loss with a prepared meal plan in overweight and obese patients: impact on cardiovascular risk reduction. , 2000, Archives of internal medicine.

[185]  Y. Matsuzawa,et al.  Suppressive effect of EPA on the incidence of coronary events in hypercholesterolemia with impaired glucose metabolism: Sub-analysis of the Japan EPA Lipid Intervention Study (JELIS). , 2009, Atherosclerosis.

[186]  J. Rosenstock,et al.  The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. , 2003, Diabetes care.

[187]  J. Rosenstock,et al.  Improved Glucose Control With Weight Loss, Lower Insulin Doses, and No Increased Hypoglycemia With Empagliflozin Added to Titrated Multiple Daily Injections of Insulin in Obese Inadequately Controlled Type 2 Diabetes , 2014, Diabetes Care.

[188]  M. Suchard,et al.  Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results. , 2000, Obesity research.

[189]  D. Mikhailidis,et al.  Efficacy and Safety of Atorvastatin in the Prevention of Cardiovascular End Points in Subjects With Type 2 Diabetes: The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN) , 2006, Diabetes Care.

[190]  Diederick Grobbee,et al.  Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. , 2008, The New England journal of medicine.

[191]  Vesa Manninen,et al.  Joint Effects of Serum Triglyceride and LDL Cholesterol and HDL Cholesterol Concentrations on Coronary Heart Disease Risk in the Helsinki Heart Study: Implications for Treatment , 1992, Circulation.

[192]  Vivian A Fonseca,et al.  Colesevelam lowers glucose and lipid levels in type 2 diabetes: the clinical evidence , 2010, Diabetes, obesity & metabolism.

[193]  G. Reaven.  Role of Insulin Resistance in Human Disease , 1988, Diabetes.

[194]  S. Costanzo,et al.  Contemporary Reviews in Cardiovascular Medicine Cardiovascular and Overall Mortality Risk in Relation to Alcohol Consumption in Patients With Cardiovascular Disease , 2010 .

[195]  K. Gadde,et al.  Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial , 2011, The Lancet.

[196]  J. Ehrman,et al.  ACSM's resource manual for guidelines for exercise testing and prescription , 2010 .

[197]  S. Bangalore,et al.  Blood Pressure Targets in Subjects With Type 2 Diabetes Mellitus/Impaired Fasting Glucose: Observations From Traditional and Bayesian Random-Effects Meta-Analyses of Randomized Trials , 2011, Circulation.

[198]  G. Bray,et al.  Prevention of Diabetes Through Lifestyle Intervention: Lessons Learned from the Diabetes Prevention Program and Outcomes Study and its Translation to Practice , 2014, Current Nutrition Reports.

[199]  G. Bray,et al.  Effects of Diet and Sodium Intake on Blood Pressure: Subgroup Analysis of the DASH-Sodium Trial , 2001, Annals of Internal Medicine.

[200]  A. Astrup,et al.  Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study , 2009, The Lancet.

[201]  S. Grundy,et al.  Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus , 2006, Diabetes Care.

[202]  S. Reis,et al.  Clinical Importance of Obesity Versus the Metabolic Syndrome in Cardiovascular Risk in Women: A Report From the Women’s Ischemia Syndrome Evaluation (WISE) Study , 2004, Circulation.

[203]  Rodica Pop-Busui,et al.  Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial , 2010, The Lancet.

[204]  P. Touboul,et al.  Fibrates Effect on Cardiovascular Risk Is Greater in Patients With High Triglyceride Levels or Atherogenic Dyslipidemia Profile: A Systematic Review and Meta-analysis , 2011, Journal of cardiovascular pharmacology.

[205]  A. Keech,et al.  Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease , 2017, The New England journal of medicine.

[206]  W. Cushman,et al.  Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial , 2015, The Lancet.

[207]  A. Wolk,et al.  Consistency with the DASH diet and incidence of heart failure. , 2009, Archives of internal medicine.

[208]  N. Marchionni,et al.  Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: a meta-analysis. , 2008, Diabetes research and clinical practice.

[209]  N. Weissman,et al.  Multicenter, placebo-controlled trial of lorcaserin for weight management. , 2010, The New England journal of medicine.

[210]  G. Reaven.  Banting lecture 1988. Role of insulin resistance in human disease. , 1988, Diabetes.

[211]  Claude Bouchard,et al.  Short Sleep Duration is Associated with Reduced Leptin Levels and Increased Adiposity: Results from the Québec Family Study , 2007, Obesity.

[212]  V. Montori,et al.  Pioglitazone and risk of bladder cancer: a meta‐analysis of controlled studies , 2013, Diabetic medicine : a journal of the British Diabetic Association.

[213]  Mark Woodward,et al.  Severe hypoglycemia and risks of vascular events and death. , 2010, The New England journal of medicine.

[214]  R. Devine,et al.  Hypoglycemia: minimizing its impact in type 2 diabetes. , 2013, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[215]  G. Bray,et al.  American association of clinical endocrinologists and american college of endocrinology position statement on the 2014 advanced framework for a new diagnosis of obesity as a chronic disease. , 2014, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[216]  Pasquale Strazzullo,et al.  Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. , 2011, European heart journal.

[217]  M. Flechtner-Mors,et al.  Metabolic and weight-loss effects of a long-term dietary intervention in obese patients. , 1999, The American journal of clinical nutrition.

[218]  K. Freedland,et al.  Anxiety and Poor Glycemic Control: A Meta-Analytic Review of the Literature , 2002, International journal of psychiatry in medicine.

[219]  M. Perri,et al.  Effects of a personalized system of skill acquisition and an educational program in the treatment of obesity. , 1998, Addictive behaviors.

[220]  T. Wadden,et al.  One‐year Weight Losses in the Look AHEAD Study: Factors Associated With Success , 2009, Obesity.

[221]  F. Greenway,et al.  Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial , 2010, The Lancet.

[222]  W C Willett,et al.  Low-density lipoprotein subclass patterns and risk of myocardial infarction. , 1988, JAMA.

[223]  I. Hirsch,et al.  Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. , 2003, JAMA.

[224]  J. Huttunen,et al.  Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. , 1987, The New England journal of medicine.

[225]  J. Fleg,et al.  Effects of Cardiac Autonomic Dysfunction on Mortality Risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial , 2010, Diabetes Care.

[226]  H. Yki-Järvinen,et al.  Comparing Daily Glycaemic Control with Insulin Glargine added to Oral Agents versus Twice-daily Premixed Insulin Alone in Type 2 Diabetes , 2004 .

[227]  R. Plodkowski,et al.  Clinical practice guidelines for healthy eating for the prevention and treatment of metabolic and endocrine diseases in adults: cosponsored by the American Association of Clinical Endocrinologists/the American College of Endocrinology and the Obesity Society. , 2013, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[228]  M. Laakso,et al.  Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial , 2002, The Lancet.

[229]  A. Garber,et al.  American Association of Clinical Endocrinologists' position statement on obesity and obesity medicine. , 2012, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[230]  L. Sjöström,et al.  XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. , 2004, Diabetes care.

[231]  J. Rosenstock,et al.  Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes. , 2005, Diabetes care.

[232]  S. Yusuf,et al.  Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[233]  William Weintraub,et al.  Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. , 2011, The New England journal of medicine.

[234]  Biao Xu,et al.  Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials , 2015, BMC Medicine.

[235]  D. Owens,et al.  Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: a 6-month ‘proof-of-concept’ study , 2011, Diabetes, obesity and metabolism.

[236]  S. Yusuf,et al.  Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study , 2009, Journal of hypertension.

[237]  D. Bliwise,et al.  Prevalence of sleep apnea and electrocardiographic disturbances in morbidly obese patients. , 2000, Obesity research.

[238]  A. Avogaro,et al.  SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System , 2017, Diabetologia.

[239]  J. Rosenstock,et al.  Sequential Intensification of Metformin Treatment in Type 2 Diabetes With Liraglutide Followed by Randomized Addition of Basal Insulin Prompted by A1C Targets , 2012, Diabetes Care.

[240]  Rury R Holman,et al.  Sulfonylurea inadequacy: efficacy of addition of insulin over 6 years in patients with type 2 diabetes in the U.K. Prospective Diabetes Study (UKPDS 57). , 2002, Diabetes care.

[241]  Improve-It Investigators.  Ezetimibe added to statin therapy after acute coronary syndromes , 2015 .

[242]  A. Lincoff,et al.  Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. , 2007, JAMA.

[243]  Kevin A Peterson,et al.  Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus , 2011 .

[244]  R. Califf,et al.  Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. , 2015, The New England journal of medicine.