Type 2 diabetes: assessing the relative risks and benefits of glucose-lowering medications.

The selection of appropriate pharmacologic therapy for any disease requires a careful assessment of benefit and risk. In the case of type 2 diabetes, this decision typically balances the benefits accrued from improved glycemic control with the risks inherent in glucose-lowering medications. This review is intended to assist therapeutic decision-making by carefully assessing the potential benefit from improved metabolic control relative to the potential risks of a wide array of currently prescribed glucose-lowering agents. Wherever possible, risks and benefits have been expressed in terms of absolute rates (events per 1000 patient-years) to facilitate cross-study comparisons. The review incorporates data from new studies (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, Action to Control Cardiovascular Risk in Diabetes, and the Veterans Affairs Diabetes Trial), as well as safety issues associated with newer glucose-lowering medications.

[1]  C. Weyer,et al.  Weight Effect of Current and Experimental Drugs for Diabetes Mellitus , 2003, Treatments in endocrinology.

[2]  H. Berlie,et al.  Thiazolidinediones and the risk of edema: a meta-analysis. , 2007, Diabetes research and clinical practice.

[3]  Jeremy A Schafer,et al.  Rosiglitazone and Pioglitazone Utilization from January 2007 Through May 2008 Associated With Five Risk-Warning Events , 2008, Journal of managed care pharmacy : JMCP.

[4]  G. Rücker,et al.  Simpson's paradox visualized: The example of the Rosiglitazone meta-analysis , 2008, BMC medical research methodology.

[5]  H. Jick,et al.  Use of thiazolidinediones and fracture risk. , 2008, Archives of internal medicine.

[6]  C. Bailey,et al.  Treatment--metformin. , 2013, Bailliere's clinical endocrinology and metabolism.

[7]  F. Greenspan,et al.  Basic & Clinical Endocrinology , 2003 .

[8]  N. Sattar,et al.  Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials , 2009, The Lancet.

[9]  N. Marchionni,et al.  Prevention of cardiovascular disease through glycemic control in type 2 diabetes: a meta-analysis of randomized clinical trials. , 2009, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[10]  G. Steineck,et al.  Obesity and treatment of diabetes with glyburide may both be risk factors for acute pancreatitis. , 2002, Diabetes care.

[11]  I. Dahabreh.  Meta-analysis of rare events: an update and sensitivity analysis of cardiovascular events in randomized trials of rosiglitazone , 2008, Clinical trials.

[12]  Alfonso T. Perez,et al.  A comparison of pioglitazone and rosiglitazone for hospitalization for acute myocardial infarction in type 2 diabetes , 2007, Pharmacoepidemiology and drug safety.

[13]  T. Hampton.  Diabetes drugs tied to fractures in women. , 2007, JAMA.

[14]  R. Holman,et al.  Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study , 2000, BMJ : British Medical Journal.

[15]  D. Bessesen.  Update on obesity. , 2008, The Journal of clinical endocrinology and metabolism.

[16]  M. Ridderstråle,et al.  Obesity and cardiovascular risk factors in type 2 diabetes: results from the Swedish National Diabetes Register , 2006, Journal of internal medicine.

[17]  R. Nesto,et al.  Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials , 2007, The Lancet.

[18]  S. Nissen,et al.  Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. , 2007, The New England journal of medicine.

[19]  Clifford Goodman,et al.  The burden of selected digestive diseases in the United States. , 2002, Gastroenterology.

[20]  P. Griffin,et al.  The Role of Dipeptidyl Peptidase IV in the Cleavage of Glucagon Family Peptides , 2003, Journal of Biological Chemistry.

[21]  B. Howard,et al.  Intensive Glycemic Control and the Prevention of Cardiovascular Events: Implications of the ACCORD, ADVANCE, and VA Diabetes Trials , 2009, Diabetes Care.

[22]  S. Schinner,et al.  Effects of Intensive Glucose Lowering in Type 2 Diabetes , 2009 .

[23]  P. Austin,et al.  New use of rosiglitazone decreased following publication of a meta‐analysis suggesting harm , 2008, Diabetic medicine : a journal of the British Diabetic Association.

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

[25]  J. Ioannidis,et al.  Challenges in meta-analysis of randomized clinical trials for rare harmful cardiovascular events: the case of rosiglitazone. , 2008, American heart journal.

[26]  M. Caulfield,et al.  Effects of torcetrapib in patients at high risk for coronary events , 2008 .

[27]  R. Holman,et al.  Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. , 1998 .

[28]  Yoon K Loke,et al.  Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. , 2007, JAMA.

[29]  Norman Fleischer,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. , 1993 .

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

[31]  P. Cryer,et al.  Hypoglycaemia: The limiting factor in the glycaemic management of Type I and Type II Diabetes* , 2002, Diabetologia.

[32]  S. Mallick.  Metformin induced acute pancreatitis precipitated by renal failure , 2004, Postgraduate Medical Journal.

[33]  E. Salpeter,et al.  Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. , 2010, The Cochrane database of systematic reviews.

[34]  P. S. Denker,et al.  Exenatide (exendin-4)-induced pancreatitis: a case report. , 2006, Diabetes care.

[35]  J. Leahy.  Economic Costs of Diabetes in the U.S. in 2007 , 2008 .

[36]  Charles Kooperberg,et al.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. , 2002, JAMA.

[37]  C. Frey,et al.  The Incidence and Case-fatality Rates of Acute Biliary, Alcoholic, and Idiopathic Pancreatitis in California, 1994-2001 , 2006, Pancreas.

[38]  J. Cramer.  A systematic review of adherence with medications for diabetes. , 2004, Diabetes care.

[39]  F. Ovalle.  10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes , 2009 .

[40]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[41]  R. Ferner,et al.  Comparative Tolerability Profiles of Oral Antidiabetic Agents , 1994, Drug safety.

[42]  G. Moneta,et al.  Intensive Diabetes Treatment and Cardiovascular Disease in Patients with Type 1 Diabetes , 2007 .

[43]  B. Fleischer,et al.  CD26: a surface protease involved in T-cell activation. , 1994, Immunology today.

[44]  P. Donnan,et al.  Adherence to prescribed oral hypoglycaemic medication in a population of patients with Type 2 diabetes: a retrospective cohort study , 2002, Diabetic medicine : a journal of the British Diabetic Association.

[45]  H. Thabet,et al.  Metformin associated acute pancreatitis. , 2002, Veterinary and human toxicology.

[46]  D. Dore,et al.  Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide. , 2009, Current medical research and opinion.

[47]  E. Topol,et al.  Risk of cardiovascular events associated with selective COX-2 inhibitors☆ , 2002 .

[48]  J. Sánchez-Payá,et al.  Obesity Is a Definitive Risk Factor of Severity and Mortality in Acute Pancreatitis: An Updated Meta-Analysis , 2006, Pancreatology.

[49]  K. Hermansen,et al.  Bodyweight Changes Associated with Antihyperglycaemic Agents in Type 2 Diabetes Mellitus , 2007, Drug safety.

[50]  入江 潤一郎,et al.  Glucose control and vascular complications in veterans with type 2 diabetes , 2009 .

[51]  C. Bailey,et al.  11 Treatment—metformin , 1988 .

[52]  F Plum,et al.  Incidence of Blindness in Relation to Diabetes: A population-based study , 1997, Diabetes Care.

[53]  Jonathan J. Shuster,et al.  Fixed vs random effects meta‐analysis in rare event studies: The Rosiglitazone link with myocardial infarction and cardiac death , 2007, Statistics in medicine.

[54]  P. Audia,et al.  Metformin-induced lactic acidosis and acute pancreatitis precipitated by diuretic, celecoxib, and candesartan-associated acute kidney dysfunction , 2008, Clinical toxicology.

[55]  J. Leahy.  Uncertain Effects of Rosiglitazone on the Risk for Myocardial Infarction and Cardiovascular Death , 2008 .

[56]  Stephen W. Sorensen,et al.  Lifetime risk for diabetes mellitus in the United States. , 2003, JAMA.

[57]  A. Spitz,et al.  Change in HbA1c as a Measure of Quality of Diabetes Care , 2006, Diabetes Care.

[58]  S. Greene,et al.  Adherence to insulin treatment, glycaemic control, and ketoacidosis in insulin-dependent diabetes mellitus , 1997, The Lancet.

[59]  C. Bailey,et al.  Dipeptidyl peptidase IV (DPP IV) inhibitors: a newly emerging drug class for the treatment of type 2 diabetes , 2006, Diabetes & vascular disease research.

[60]  A. Murray,et al.  Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. , 2005, Journal of the American Society of Nephrology : JASN.

[61]  J. Cramer.  A Systematic Review of Adherence With Medications for Diabetes , 2004 .

[62]  C. Pitchumoni,et al.  Drug-Induced Pancreatitis: An Update , 2005, Journal of clinical gastroenterology.

[63]  C. Furberg,et al.  Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis , 2009, Canadian Medical Association Journal.

[64]  M. Roizen.  General and Abdominal Adiposity and Risk of Death in Europe , 2009 .

[65]  M. Laakso,et al.  Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. , 1998, The New England journal of medicine.

[66]  J. Racoosin,et al.  Suicidality in pediatric patients treated with antidepressant drugs. , 2006, Archives of general psychiatry.

[67]  N. Marchionni,et al.  Winners and losers at the rosiglitazone gamble A meta-analytical approach at the definition of the cardiovascular risk profile of rosiglitazone. , 2008, Diabetes research and clinical practice.

[68]  A. Grey.  Thiazolidinedione‐induced skeletal fragility – mechanisms and implications , 2009, Diabetes, obesity & metabolism.

[69]  G. Krishnarajah,et al.  Hypoglycaemic symptoms, treatment satisfaction, adherence and their associations with glycaemic goal in patients with type 2 diabetes mellitus: findings from the Real‐Life Effectiveness and Care Patterns of Diabetes Management (RECAP‐DM) Study , 2008, Diabetes, obesity & metabolism.

[70]  R. Carmona-Sánchez,et al.  Obesity: A Risk Factor for Severe Acute Biliary and Alcoholic Pancreatitis , 1998, American Journal of Gastroenterology.

[71]  J. Lau,et al.  Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. , 2007, JAMA.

[72]  SyedRizwanudden Ahmad,et al.  Exenatide and rare adverse events. , 2008, The New England journal of medicine.

[73]  G. Gensini,et al.  Pioglitazone and cardiovascular risk. A comprehensive meta‐analysis of randomized clinical trials , 2008, Diabetes, obesity & metabolism.

[74]  G. McMahon,et al.  Intensive glycemic control in the ACCORD and ADVANCE trials. , 2008, The New England journal of medicine.

[75]  A. Feller,et al.  CD26 Antigen is a Surface Dipeptidyl Peptidase IV (DPPIV) as Characterized by Monoclonal Antibodies Clone Til‐19‐4‐7 and 4EL1C7 , 1990, Scandinavian journal of immunology.

[76]  M. Thun,et al.  Intentional Weight Loss and Mortality among Overweight Individuals with Diabetes O R I G I N a L a R T I C L E , 2022 .

[77]  E. Erdmann,et al.  Effects of pioglitazone on major adverse cardiovascular events in high-risk patients with type 2 diabetes: results from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive 10). , 2008, American heart journal.

[78]  C. Camargo,et al.  Increasing United States hospital admissions for acute pancreatitis, 1988-2003. , 2007, Annals of epidemiology.

[79]  R. Patterson,et al.  Increased Risk of Acute Pancreatitis and Biliary Disease Observed in Patients With Type 2 Diabetes , 2009, Diabetes Care.

[80]  R. Holman,et al.  Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) , 1998, The Lancet.

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

[82]  C. Meinert,et al.  A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results. , 1970, Diabetes.

[83]  Plamen Nikolov,et al.  Economic Costs of Diabetes in the U.S. in 2002 , 2003, Diabetes care.