A review of treatment response in type 2 diabetes: Assessing the role of patient heterogeneity

Diabetes, Obesity and Metabolism

Volumn 12, Issue 10, 2010, Pages 845-857

  Cantrell, R A ^a   Alatorre, C I ^a   Davis, E J ^b   Zarotsky, V ^b   Le Nestour, E ^c   Carter, G Cuyún ^a   Goetz, I ^a   Paczkowski, R ^a   Sierra Johnson, J ^a,d  

^a ELI LILLY AND COMPANY   (United States)

^b i3 Innovus   (United States)

^c I3 Research   (France)

^d MAYO CLINIC   (United States)

Author keywords

Glycated hemoglobin; Heterogeneity; Heterogeneity of treatment response; Population characteristics; Treatment response; Type 2 diabetes

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ACARBOSE; ALBUMIN; ALPHA GLUCOSIDASE INHIBITOR; AMYLIN; C PEPTIDE; EXENDIN 4; GLIBENCLAMIDE; GLIMEPIRIDE; GLIPIZIDE; GLUCOSE; HEMOGLOBIN A1C; INSULIN; LIPID; METFORMIN; NATEGLINIDE; ORAL ANTIDIABETIC AGENT; PIOGLITAZONE; PRAMLINTIDE; REPAGLINIDE; ROSIGLITAZONE; SITAGLIPTIN; SULFONYLUREA; VILDAGLIPTIN; VOGLIBOSE;

ADIPOSE TISSUE; ALBUMIN BLOOD LEVEL; BEHAVIOR; BODY COMPOSITION; CLINICAL DECISION MAKING; COCHRANE LIBRARY; COMORBIDITY; DATA BASE; DEMOGRAPHY; DYSLIPIDEMIA; ECONOMIC ASPECT; GLUCOSE BLOOD LEVEL; HUMAN; INSULIN SENSITIVITY; INSULIN TREATMENT; LIPID BLOOD LEVEL; MEDLINE; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; OUTCOME ASSESSMENT; PATIENT SELECTION; RACE; REVIEW; SENSITIVITY ANALYSIS; SEX; SINGLE DRUG DOSE; SOCIAL ASPECT; TREATMENT DURATION; TREATMENT RESPONSE;

EID: 77956161103     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/j.1463-1326.2010.01248.x     Document Type: Review

References (53)

1. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diab Res Clin Pract 2010, 87:4-14.
2. Diabetes: fact sheet No. 312. 2009, http://www.who.int/mediacentre/factsheets/fs312/en, World Health Organization (WHO), Available from URL:, Accessed 14 May 2010.
3. Diabetes data & trends: prevalence of diabetes. http://www.cdc.gov/diabetes/statistics/prev/national/figpersons.htm, Centers for Disease Control and Prevention (CDC), Available from URL:, Accessed 23 July 2009.
4. Nathan DM, Buse JB, Davidson M. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009, 32:193-203.
5. Shomali ME. Practical applications of therapy with a glucagon-like peptide-1 receptor agonist. J Fam Pract 2009, 58:S35-S43.
6. Greenfield S, Kravitz R, Duan N, Kaplan SH. Heterogeneity of treatment effects: implications for guidelines, payment, and quality assessment. Am J Med 2007, 120:S3-S9.
7. Kravitz RL, Duan N, Braslow J. Evidence-based medicine, heterogeneity of treatment effects, and the trouble with averages. Milbank Q 2004, 82:661-687.
8. The guidelines manual. London: National Institute for Health and Clinical Excellence. 2006, http://www.nice.org.uk, National Institute for Health and Clinical Excellence, Available from URL:, Accessed 14 May 2010.
9. Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999, 281:2005-2012.
10. Alemzadeh R, Ellis J, Calhoun M, Kichler J. Predictors of metabolic control at one year in a population of pediatric patients with type 2 diabetes mellitus: a retrospective study. J Pediatr Endocrinol Metab 2006, 19:1141-1149.
11. Cook CB, Lyles RH, El-Kebbi I. The potentially poor response to outpatient diabetes care in urban African-Americans. Diabetes Care 2001, 24:209-215.
12. Cozma LS, Luzio SD, Dunseath GJ, Underwood PM, Owens DR. Beta-cell response during a meal test: a comparative study of incremental doses of repaglinide in type 2 diabetic patients. Diabetes Care 2005, 28:1001-1007.
13. Osterbrand M, Fahlen M, Oden A, Eliasson B. A method to predict the metabolic effects of changes in insulin treatment in subgroups of a large population based patient cohort. Eur J Epidemiol 2007, 22:151-157.
14. Duckworth W, Marcelli M, Padden M. Improvements in glycemic control in type 2 diabetes patients switched from sulfonylurea coadministered with metformin to glyburide-metformin tablets. J Manag Care Pharm 2003, 9:256-262.
15. Izumi R, Hurt J, Maki KC, Bell M, Zavras AI, McCamish M. Clinical predictors of glycosylated hemoglobin response to thiazolidinedione therapy. Diabetes Technol Ther 2007, 9:553-561.
16. Murata GH, Shah JH, Hoffman RM. Intensified blood glucose monitoring improves glycemic control in stable, insulin-treated veterans with type 2 diabetes: the Diabetes Outcomes in Veterans Study (DOVES). Diabetes Care 2003, 26:1759-1763.
17. Kim YM, Cha BS, Kim DJ. Predictive clinical parameters for therapeutic efficacy of rosiglitazone in Korean type 2 diabetes mellitus. Diabetes Res Clin Pract 2005, 67:43-52.
18. Bloomgarden ZT, Dodis R, Viscoli CM, Holmboe ES, Inzucchi SE. Lower baseline glycemia reduces apparent oral agent glucose-lowering efficacy: a meta-regression analysis. Diabetes Care 2006, 29:2137-2139.
19. Hirose T, Miyashita Y, Takagi M, Sumitani S, Kouhara H, Kasayama S. Characteristics of type 2 diabetic patients responding to voglibose administration as an adjunct to sulfonylurea. Diabetes Res Clin Pract 2001, 54:9-15.
20. Mori Y, Ishii H, Hikita M, Tajima N. Clinical characteristics of nateglinide response as assessed by insulinogenic indices: preliminary study to determine an optimal indication for nateglinide. Adv Ther 2003, 20:352-359.
21. Taverna MJ, Pacher N, Bruzzo F, Slama G, Selam JL. Beta-cell function evaluated by HOMA as a predictor of secondary sulphonylurea failure in Type 2 diabetes. Diabet Med 2001, 18:584-588.
22. Singh J, Unnikrishnan AG, Agrawal NK, Singh SK, Agrawal JK. Immunoreactive insulin response to a single dose of glimepiride in lean type 2 diabetic subjects. J Assoc Physicians India 2002, 50:1232-1235.
23. Miyazaki Y, De Filippis E, Bajaj M. Predictors of improved glycemic control with rosiglitazone therapy in type 2 diabetic patients: a practical approach for the primary care physician. Br J Diabetes Vasc Dis 2005, 5:28-35.
24. Araki T, Emoto M, Yokoyama H. Insulin resistance index as a predictor for pioglitazone treatment in type 2 diabetes. Osaka City Med J 2005, 51:19-25.
25. Bell DS, Ovalle F. Outcomes of initiation of therapy with once-daily combination of a thiazolidinedione and a biguanide at an early stage of type 2 diabetes. Diabetes Obes Metab 2004, 6:363-366.
26. Oli JM, Adeyemo AA, Okafor GO. Beta cell function and response to treatment in Nigerians with Type 2 diabetes mellitus. Diabetes Res Clin Pract 2005, 69:196-204.
27. Donnelly LA, Doney AS, Hattersley AT, Morris AD, Pearson ER. The effect of obesity on glycaemic response to metformin or sulphonylureas in Type 2 diabetes. Diabet Med 2006, 23:128-133.
28. Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA 2007, 298:1180-1188.
29. Benoit SR, Fleming R, Philis-Tsimikas A, Ji M. Predictors of glycemic control among patients with Type 2 diabetes: a longitudinal study. BMC Public Health 2005, 5:36.
30. Nichols GA, Hillier TA, Javor K, Brown JB. Predictors of glycemic control in insulin-using adults with type 2 diabetes. Diabetes Care 2000, 23:273-277.
31. Hiramatsu S, Tajiri Y, Karashima T. Lower plasma adiponectin concentration predicts the efficacy of pioglitazone in diabetic patients. Diabetes Obes Metab 2004, 6:231-233.
32. Hammarstedt A, Pihlajamaki J, Graham TE. High circulating levels of RBP4 and mRNA levels of aP2, PGC-1alpha and UCP-2 predict improvement in insulin sensitivity following pioglitazone treatment of drug-naive type 2 diabetic subjects. J Intern Med 2008, 263:440-449.
33. Davidson M, Meyer PM, Haffner S. Increased high-density lipoprotein cholesterol predicts the pioglitazone-mediated reduction of carotid intima-media thickness progression in patients with type 2 diabetes mellitus. Circulation 2008, 117:2123-2130.
34. King AB, Armstrong DU. Lipid response to pioglitazone in diabetic patients: clinical observations from a retrospective chart review. Diabetes Technol Ther 2002, 4:145-151.
35. Rodriguez-Segade S, Rodriguez J, Mayan D, Camina F. Plasma albumin concentration is a predictor of HbA1c among type 2 diabetic patients, independently of fasting plasma glucose and fructosamine. Diabetes Care 2005, 28:437-439.
36. Charpentier G, Vaur L, Halimi S. Predictors of response to glimepiride in patients with type 2 diabetes mellitus. Diabetes Metab 2001, 27:563-571.
37. Chen YN, Chen SY, Zeng LJ, Ran JM, Wu MY. Progressive decrease of proinsulin secretion in sulphonylurea-treated type 2 diabetes. Br J Biomed Sci 2005, 62:5-8.
38. Spoelstra JA, Stolk RP, Heerdink ER. Refill compliance in type 2 diabetes mellitus: a predictor of switching to insulin therapy? Pharmacoepidemiol Drug Saf 2003, 12:121-127.
39. Murata GH, Duckworth WC, Shah JH, Wendel CS, Hoffman RM. Sources of glucose variability in insulin-treated type 2 diabetes: the Diabetes Outcomes in Veterans Study (DOVES). Clin Endocrinol (Oxf) 2004, 60:451-456.
40. Spoelstra JA, Stol RP, de Bruyne MC. Factors associated with switching from oral hypoglycaemic agents to insulin therapy. Neth J Med 2002, 60:243-248.
41. Balkrishnan R, Rajagopalan R, Camacho FT, Huston SA, Murray FT, Anderson RT. Predictors of medication adherence and associated health care costs in an older population with type 2 diabetes mellitus: a longitudinal cohort study. Clin Ther 2003, 25:2958-2971.
42. Aikens JE, Perkins DW, Piette JD, Lipton B. Association between depression and concurrent Type 2 diabetes outcomes varies by diabetes regimen. Diabet Med 2008, 25:1324-1329.
43. Wagner JA, Tennen H. History of major depressive disorder and diabetes outcomes in diet- and tablet-treated post-menopausal women: a case control study. Diabet Med 2007, 24:211-216.
44. Krein SL, Bingham CR, McCarthy JF, Mitchinson A, Payes J, Valenstein M. Diabetes treatment among VA patients with comorbid serious mental illness. Psychiatr Serv 2006, 57:1016-1021.
45. Schectman JM, Nadkarni MM, Voss JD. The association between diabetes metabolic control and drug adherence in an indigent population. Diabetes Care 2002, 25:1015-1021.
46. Harris MI. Racial and ethnic differences in health care access and health outcomes for adults with type 2 diabetes. Diabetes Care 2001, 24:454-459.
47. Wendel CS, Shah JH, Duckworth WC, Hoffman RM, Mohler MJ, Murata GH. Racial and ethnic disparities in the control of cardiovascular disease risk factors in Southwest American veterans with type 2 diabetes: the Diabetes Outcomes in Veterans Study. BMC Health Serv Res 2006, 6:58.
48. Reisig V, Reitmeir P, Doring A, Rathmann W, Mielck A. Social inequalities and outcomes in type 2 diabetes in the German region of Augsburg. A cross-sectional survey. Int J Public Health 2007, 52:158-165.
49. Goudswaard AN, Stolk RP, Zuithoff P, Rutten GE. Patient characteristics do not predict poor glycaemic control in type 2 diabetes patients treated in primary care. Eur J Epidemiol 2004, 19:541-545.
50. Jotkowitz AB, Rabinowitz G, Raskin SA, Weitzman R, Epstein L, Porath A. Do patients with diabetes and low socioeconomic status receive less care and have worse outcomes? A national study. Am J Med 2006, 119:665-669.
51. Schillinger D, Grumbach K, Piette J. Association of health literacy with diabetes outcomes. JAMA 2002, 288:475-482.
52. Saudek CD, Derr RL, Kalyani RR. Assessing glycemia in diabetes using self-monitoring blood glucose and hemoglobin A1c. JAMA 2006, 295:1688-1697.
53. Guidance for industry: diabetes mellitus: developing drugs and therapeutic biologics for treatment and prevention. 2008, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071624.pdf, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Available from URL:, Accessed 17 June 2010.