Research Original Investigation
Glucose-Lowering Medication for Diabetes
7. Boussageon R, Supper I, Bejan-Angoulvant T, et al. Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials. PLoS Med. 2012;9(4): e1001204.
14. WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC Classification and DDD Assignment 2014. Oslo, Sweden: WHO Collaborating Centre for Drug Statistics Methodology; 2013.
8. Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011;13(3):221-228.
15. Menchine MD, Wiechmann W, Peters AL, Arora S. Trends in diabetes-related visits to US EDs from 1997 to 2007. Am J Emerg Med. 2012;30(5):754-758.
9. Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med. 2011;154(9):602-613. 10. Desai NR, Shrank WH, Fischer MA, et al. Patterns of medication initiation in newly diagnosed diabetes mellitus: quality and cost implications. Am J Med. 2012;125(3):e1-e7. 11. Grant RW, Pabon-Nau L, Ross KM, Youatt EJ, Pandiscio JC, Park ER. Diabetes oral medication initiation and intensification: patient views compared with current treatment guidelines. Diabetes Educ. 2011;37(1):78-84. 12. Huang ES, Brown SE, Ewigman BG, Foley EC, Meltzer DO. Patient perceptions of quality of life with diabetes-related complications and treatments. Diabetes Care. 2007;30(10):2478-2483. 13. Food and Drug Administration. Byetta-Label and Approval History. 2014. http://www.accessdata .fda.gov/scripts/cder/drugsatfda/index.cfm?CFID =34450006&CFTOKEN=ed70a376f72834f9 -62B65790-B0FB-077D -CA6B7E5F52D6A221#apphist. Accessed July 17, 2014.
16. Gagne JJ, Glynn RJ, Avorn J, Levin R, Schneeweiss S. A combined comorbidity score predicted mortality in elderly patients better than existing scores. J Clin Epidemiol. 2011;64(7):749-759. 17. Spreeuwenberg MD, Bartak A, Croon MA, et al. The multiple propensity score as control for bias in the comparison of more than two treatment arms: an introduction from a case study in mental health. Med Care. 2010;48(2):166-174. 18. Hux JE, Ivis F, Flintoft V, Bica A. Diabetes in Ontario: determination of prevalence and incidence using a validated administrative data algorithm. Diabetes Care. 2002;25(3):512-516. 19. Glynn RJ, Monane M, Gurwitz JH, Choodnovskiy I, Avorn J. Agreement between drug treatment data and a discharge diagnosis of diabetes mellitus in the elderly. Am J Epidemiol. 1999;149(6):541-549. 20. Kahn SE, Haffner SM, Heise MA, et al; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355(23):2427-2443. 21. Hampp C, Borders-Hemphill V, Moeny DG, Wysowski DK. Use of antidiabetic drugs in the U.S., 2003-2012. Diabetes Care. 2014;37(5):1367-1374.
22. Mayor S. European drug regulators publish their evaluation of rosiglitazone. BMJ. 2010;341: c7278. 23. DeFronzo RA, Eldor R, Abdul-Ghani M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. Diabetes Care. 2013;36(suppl 2):S127-S138. 24. Peyrot M, Rubin RR, Lauritzen T, et al; International DAWN Advisory Panel. Resistance to insulin therapy among patients and providers: results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study. Diabetes Care. 2005;28(11):2673-2679. 25. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359 (15):1577-1589. 26. Roumie CL, Hung AM, Greevy RA, et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med. 2012;157(9):601-610. 27. Lipscombe LL, Gomes T, Lévesque LE, Hux JE, Juurlink DN, Alter DA. Thiazolidinediones and cardiovascular outcomes in older patients with diabetes. JAMA. 2007;298(22):2634-2643. 28. Starner CI, Schafer JA, Heaton AH, Gleason PP. Rosiglitazone and pioglitazone utilization from January 2007 through May 2008 associated with five risk-warning events. J Manag Care Pharm. 2008;14(6):523-531.
Invited Commentary
Initial Therapy for Diabetes Mellitus Jodi B. Segal, MD, MPH; Nisa M. Maruthur, MD, MHS
Berkowitz and colleagues1 assert that there is little comparative effectiveness evidence to guide initial selection of therapy for diabetes mellitus. They therefore conducted this rigorous study to determine effects attributable to initial oral glucoselowering agents. With a retrospective cohort design using 4 years of recent claims data from a large national insurer, they investigated outcomes from 4 classes of oral diabetes medications (metformin, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase 4 inhibitors). In their adjusted models, initiation of therapy with a sulfonylurea, thiazolidinediRelated article page 1955 one, or dipeptidyl phosphatase 4 inhibitor was associated with an increased hazard of treatment intensification (addition of another drug) relative to first therapy with metformin, without greater clinical benefits (and often more shortterm adverse events). The authors noted that only 57.8% of individuals in their data set began pharmaceutical management of their diabetes with metformin. This study understandably omitted the newest class of medications—the sodiumdependent glucose transporter 2 inhibitors—because the first drug was not approved in the United States until March 2013. 1962
Less understandable is the exclusion of injectable medications from the glucagon-like peptide 1 agonist class despite their approval for use as monotherapy and availability since 2005. This meticulously conducted study, however, adds modestly to what is already known on this topic. Existing evidence is strong on the use of metformin as first-line therapy. Although the choice of adjunctive agent for treatment intensification remains uncertain (prompting the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study, under way since 2013), first-line therapy should be metformin in patients without contraindications. The Agency for Healthcare Research and Quality has commissioned 2 reviews2,3 on the comparative effectiveness of oral therapy for treatment of type 2 diabetes—the first in 2007 and the second in 2011. An update of this review is under way, with results expected in spring 2015. As early as the first review, it was clear that the comparative effectiveness literature supports first-line treatment with metformin; metformin is equivalent or superior to most other drugs in lowering hemoglobin A1c levels but with less weight gain and less hypoglycemia than most.3 The effect on longer-term clinical outcomes remains uncertain; the
JAMA Internal Medicine December 2014 Volume 174, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Fudan University User on 05/11/2015
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Glucose-Lowering Medication for Diabetes
Original Investigation Research
study in JAMA Internal Medicine contributes little to this knowledge base given that the median follow-up time was just longer than 1 year. Guidelines published after the publication of the first Agency for Healthcare Research and Quality systematic review, including those from the American Diabetes Association, the American Association of Clinical Endocrinologists, the American College of Endocrinology, the European Association for the Study of Diabetes, and the UK National Institute for Health and Care Excellence, largely recommend metformin as first-line therapy.4 The joint consensus statement from the American Association of Clinical Endocrinologists/American College of Endocrinology5 described metformin as the “cornerstone of monotherapy” because of its safety and efficacy. However, 4 other drugs were also recommended as possible first-line medication options in its monotherapy algorithm. Thus, the superiority of metformin as first-line therapy is not novel, although the outcome of treatment intensification is not a commonly reported outcome and may indeed be important to patients. Incomplete conformity with guideline recommendations is well recognized. Recent work6 by the HMO Research Network described initial therapy used by patients in health maintenance organizations across the United States. This retrospective cohort study6 included 241 327 patients from 11 US health systems from 2005 through 2010. Within 6 months of diabetes diagnosis, only 40% of patients had started taking medication, although patients with higher hemoglobin A1c levels were more likely to begin taking medication. Seventy-five percent of the initial prescriptions were for metformin; it is unlikely that 25% of the population had contraindications to its use. The ideal percentage of patients whose initial prescription is for metformin is a moving target; physicians, supported by evidence,7 are increasingly using metformin in patients with mild to moderate renal insufficiency who would previously have been considered to have contraindications to its use. The percentage of patients excluded from an attempt at metformin therapy should be small. As in the study by Berkowitz and colleagues, the health maintenance organization researchers also examined the time to intensification of therapy. Among 41 233 patients taking medication, 33% and 45% had treatment intensified within 6 ARTICLE INFORMATION Author Affiliations: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. Corresponding Author: Jodi B. Segal, MD, MPH, Department of Medicine, Johns Hopkins University School of Medicine, 624 N Broadway, Room 644, Baltimore, MD 21205 ([email protected]). Published Online: October 27, 2014. doi:10.1001/jamainternmed.2014.4296. Conflict of Interest Disclosures: None reported. REFERENCES 1. Berkowitz SA, Krumme AA, Avorn J, et al. Initial choice of oral glucose-lowering medication for diabetes mellitus: a patient-centered comparative effectiveness study [published online October 27,
and 12 months after beginning their first medicine. This initial intensification was most often done with increased dosage of the first medication. The figure in the study by Berkowitz et al shows, comparably, that roughly 25% of patients initially using metformin and 40% of those using other medications intensified therapy in the first 12 months. Unlike in the study by Berkowitz et al, Raebel and colleagues6 did not stratify intensification by the initial therapy. We wonder, however, about the choice of addition of medication as the only indicator of treatment intensification rather than a dosage increase. Raebel and colleagues6 considered either one to be an indicator of intensification. This consideration is particularly germane to use of metformin because the slow titration of metformin typically reduces gastrointestinal adverse effects. This slow increase of the dose over time may delay the time until a second agent is added without indicating the superiority of metformin. We note, as well, that the authors did not have the necessary data (laboratory results) to confirm that the delayed initiation of a second agent was due to sustained good control with a single agent, but we do not think that a physician’s response to poor control would differ by drug. The published evidence to date has not focused on the need for intensification of therapy as an outcome, and the authors of this new study appropriately cite literature on this patientcentered outcome. We find this observation to be the most compelling rationale for this article: that patients consider treatment intensification to be failure. Although this statement has implications for initial choice of therapy, it has greater implications for patient-physician communication about diabetes. Although it is true in some patients that the need to add an additional medication is due to their imperfect adherence to diet and exercise or adherence to the first prescribed drug, in many other patients it reflects the expected progression of disease and worsening insulin sensitivity and declining β-cell function. Whereas in hypertension management the use of several submaximal doses of medication is supported by evidence and well accepted by patients, this approach is not the case in diabetes management. Reframing the addition of medication as a necessary step for wellness and health maintenance may go a long way toward patient acceptance of intensification as an unfortunate but necessary part of good self-care.
2014]. JAMA Intern Med. doi:10.1001 /jamainternmed.2014.5294. 2. Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med. 2011;154(9):602-613. 3. Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007;147(6):386-399. 4. Bennett WL, Odelola OA, Wilson LM, et al. Evaluation of guideline recommendations on oral medications for type 2 diabetes mellitus: a systematic review. Ann Intern Med. 2012;156(1, pt 1):27-36.
Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15(6):540-559. 6. Raebel MA, Ellis JL, Schroeder EB, et al. Intensification of antihyperglycemic therapy among patients with incident diabetes: a Surveillance Prevention and Management of Diabetes Mellitus (SUPREME-DM) study. Pharmacoepidemiol Drug Saf. 2014;23(7):699-710. 7. Raebel MA, Xu S, Goodrich GK, et al. Initial antihyperglycemic drug therapy among 241 327 adults with newly identified diabetes from 2005 through 2010: a Surveillance, Prevention, and Management of Diabetes Mellitus (SUPREME-DM) study. Ann Pharmacother. 2013;47(10):1280-1291.
5. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical
jamainternalmedicine.com
JAMA Internal Medicine December 2014 Volume 174, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Fudan University User on 05/11/2015
1963
Glucose-Lowering Medication for Diabetes
7. Boussageon R, Supper I, Bejan-Angoulvant T, et al. Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials. PLoS Med. 2012;9(4): e1001204.
14. WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC Classification and DDD Assignment 2014. Oslo, Sweden: WHO Collaborating Centre for Drug Statistics Methodology; 2013.
8. Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011;13(3):221-228.
15. Menchine MD, Wiechmann W, Peters AL, Arora S. Trends in diabetes-related visits to US EDs from 1997 to 2007. Am J Emerg Med. 2012;30(5):754-758.
9. Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med. 2011;154(9):602-613. 10. Desai NR, Shrank WH, Fischer MA, et al. Patterns of medication initiation in newly diagnosed diabetes mellitus: quality and cost implications. Am J Med. 2012;125(3):e1-e7. 11. Grant RW, Pabon-Nau L, Ross KM, Youatt EJ, Pandiscio JC, Park ER. Diabetes oral medication initiation and intensification: patient views compared with current treatment guidelines. Diabetes Educ. 2011;37(1):78-84. 12. Huang ES, Brown SE, Ewigman BG, Foley EC, Meltzer DO. Patient perceptions of quality of life with diabetes-related complications and treatments. Diabetes Care. 2007;30(10):2478-2483. 13. Food and Drug Administration. Byetta-Label and Approval History. 2014. http://www.accessdata .fda.gov/scripts/cder/drugsatfda/index.cfm?CFID =34450006&CFTOKEN=ed70a376f72834f9 -62B65790-B0FB-077D -CA6B7E5F52D6A221#apphist. Accessed July 17, 2014.
16. Gagne JJ, Glynn RJ, Avorn J, Levin R, Schneeweiss S. A combined comorbidity score predicted mortality in elderly patients better than existing scores. J Clin Epidemiol. 2011;64(7):749-759. 17. Spreeuwenberg MD, Bartak A, Croon MA, et al. The multiple propensity score as control for bias in the comparison of more than two treatment arms: an introduction from a case study in mental health. Med Care. 2010;48(2):166-174. 18. Hux JE, Ivis F, Flintoft V, Bica A. Diabetes in Ontario: determination of prevalence and incidence using a validated administrative data algorithm. Diabetes Care. 2002;25(3):512-516. 19. Glynn RJ, Monane M, Gurwitz JH, Choodnovskiy I, Avorn J. Agreement between drug treatment data and a discharge diagnosis of diabetes mellitus in the elderly. Am J Epidemiol. 1999;149(6):541-549. 20. Kahn SE, Haffner SM, Heise MA, et al; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355(23):2427-2443. 21. Hampp C, Borders-Hemphill V, Moeny DG, Wysowski DK. Use of antidiabetic drugs in the U.S., 2003-2012. Diabetes Care. 2014;37(5):1367-1374.
22. Mayor S. European drug regulators publish their evaluation of rosiglitazone. BMJ. 2010;341: c7278. 23. DeFronzo RA, Eldor R, Abdul-Ghani M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. Diabetes Care. 2013;36(suppl 2):S127-S138. 24. Peyrot M, Rubin RR, Lauritzen T, et al; International DAWN Advisory Panel. Resistance to insulin therapy among patients and providers: results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study. Diabetes Care. 2005;28(11):2673-2679. 25. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359 (15):1577-1589. 26. Roumie CL, Hung AM, Greevy RA, et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med. 2012;157(9):601-610. 27. Lipscombe LL, Gomes T, Lévesque LE, Hux JE, Juurlink DN, Alter DA. Thiazolidinediones and cardiovascular outcomes in older patients with diabetes. JAMA. 2007;298(22):2634-2643. 28. Starner CI, Schafer JA, Heaton AH, Gleason PP. Rosiglitazone and pioglitazone utilization from January 2007 through May 2008 associated with five risk-warning events. J Manag Care Pharm. 2008;14(6):523-531.
Invited Commentary
Initial Therapy for Diabetes Mellitus Jodi B. Segal, MD, MPH; Nisa M. Maruthur, MD, MHS
Berkowitz and colleagues1 assert that there is little comparative effectiveness evidence to guide initial selection of therapy for diabetes mellitus. They therefore conducted this rigorous study to determine effects attributable to initial oral glucoselowering agents. With a retrospective cohort design using 4 years of recent claims data from a large national insurer, they investigated outcomes from 4 classes of oral diabetes medications (metformin, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase 4 inhibitors). In their adjusted models, initiation of therapy with a sulfonylurea, thiazolidinediRelated article page 1955 one, or dipeptidyl phosphatase 4 inhibitor was associated with an increased hazard of treatment intensification (addition of another drug) relative to first therapy with metformin, without greater clinical benefits (and often more shortterm adverse events). The authors noted that only 57.8% of individuals in their data set began pharmaceutical management of their diabetes with metformin. This study understandably omitted the newest class of medications—the sodiumdependent glucose transporter 2 inhibitors—because the first drug was not approved in the United States until March 2013. 1962
Less understandable is the exclusion of injectable medications from the glucagon-like peptide 1 agonist class despite their approval for use as monotherapy and availability since 2005. This meticulously conducted study, however, adds modestly to what is already known on this topic. Existing evidence is strong on the use of metformin as first-line therapy. Although the choice of adjunctive agent for treatment intensification remains uncertain (prompting the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study, under way since 2013), first-line therapy should be metformin in patients without contraindications. The Agency for Healthcare Research and Quality has commissioned 2 reviews2,3 on the comparative effectiveness of oral therapy for treatment of type 2 diabetes—the first in 2007 and the second in 2011. An update of this review is under way, with results expected in spring 2015. As early as the first review, it was clear that the comparative effectiveness literature supports first-line treatment with metformin; metformin is equivalent or superior to most other drugs in lowering hemoglobin A1c levels but with less weight gain and less hypoglycemia than most.3 The effect on longer-term clinical outcomes remains uncertain; the
JAMA Internal Medicine December 2014 Volume 174, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Fudan University User on 05/11/2015
jamainternalmedicine.com
Glucose-Lowering Medication for Diabetes
Original Investigation Research
study in JAMA Internal Medicine contributes little to this knowledge base given that the median follow-up time was just longer than 1 year. Guidelines published after the publication of the first Agency for Healthcare Research and Quality systematic review, including those from the American Diabetes Association, the American Association of Clinical Endocrinologists, the American College of Endocrinology, the European Association for the Study of Diabetes, and the UK National Institute for Health and Care Excellence, largely recommend metformin as first-line therapy.4 The joint consensus statement from the American Association of Clinical Endocrinologists/American College of Endocrinology5 described metformin as the “cornerstone of monotherapy” because of its safety and efficacy. However, 4 other drugs were also recommended as possible first-line medication options in its monotherapy algorithm. Thus, the superiority of metformin as first-line therapy is not novel, although the outcome of treatment intensification is not a commonly reported outcome and may indeed be important to patients. Incomplete conformity with guideline recommendations is well recognized. Recent work6 by the HMO Research Network described initial therapy used by patients in health maintenance organizations across the United States. This retrospective cohort study6 included 241 327 patients from 11 US health systems from 2005 through 2010. Within 6 months of diabetes diagnosis, only 40% of patients had started taking medication, although patients with higher hemoglobin A1c levels were more likely to begin taking medication. Seventy-five percent of the initial prescriptions were for metformin; it is unlikely that 25% of the population had contraindications to its use. The ideal percentage of patients whose initial prescription is for metformin is a moving target; physicians, supported by evidence,7 are increasingly using metformin in patients with mild to moderate renal insufficiency who would previously have been considered to have contraindications to its use. The percentage of patients excluded from an attempt at metformin therapy should be small. As in the study by Berkowitz and colleagues, the health maintenance organization researchers also examined the time to intensification of therapy. Among 41 233 patients taking medication, 33% and 45% had treatment intensified within 6 ARTICLE INFORMATION Author Affiliations: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. Corresponding Author: Jodi B. Segal, MD, MPH, Department of Medicine, Johns Hopkins University School of Medicine, 624 N Broadway, Room 644, Baltimore, MD 21205 ([email protected]). Published Online: October 27, 2014. doi:10.1001/jamainternmed.2014.4296. Conflict of Interest Disclosures: None reported. REFERENCES 1. Berkowitz SA, Krumme AA, Avorn J, et al. Initial choice of oral glucose-lowering medication for diabetes mellitus: a patient-centered comparative effectiveness study [published online October 27,
and 12 months after beginning their first medicine. This initial intensification was most often done with increased dosage of the first medication. The figure in the study by Berkowitz et al shows, comparably, that roughly 25% of patients initially using metformin and 40% of those using other medications intensified therapy in the first 12 months. Unlike in the study by Berkowitz et al, Raebel and colleagues6 did not stratify intensification by the initial therapy. We wonder, however, about the choice of addition of medication as the only indicator of treatment intensification rather than a dosage increase. Raebel and colleagues6 considered either one to be an indicator of intensification. This consideration is particularly germane to use of metformin because the slow titration of metformin typically reduces gastrointestinal adverse effects. This slow increase of the dose over time may delay the time until a second agent is added without indicating the superiority of metformin. We note, as well, that the authors did not have the necessary data (laboratory results) to confirm that the delayed initiation of a second agent was due to sustained good control with a single agent, but we do not think that a physician’s response to poor control would differ by drug. The published evidence to date has not focused on the need for intensification of therapy as an outcome, and the authors of this new study appropriately cite literature on this patientcentered outcome. We find this observation to be the most compelling rationale for this article: that patients consider treatment intensification to be failure. Although this statement has implications for initial choice of therapy, it has greater implications for patient-physician communication about diabetes. Although it is true in some patients that the need to add an additional medication is due to their imperfect adherence to diet and exercise or adherence to the first prescribed drug, in many other patients it reflects the expected progression of disease and worsening insulin sensitivity and declining β-cell function. Whereas in hypertension management the use of several submaximal doses of medication is supported by evidence and well accepted by patients, this approach is not the case in diabetes management. Reframing the addition of medication as a necessary step for wellness and health maintenance may go a long way toward patient acceptance of intensification as an unfortunate but necessary part of good self-care.
2014]. JAMA Intern Med. doi:10.1001 /jamainternmed.2014.5294. 2. Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med. 2011;154(9):602-613. 3. Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007;147(6):386-399. 4. Bennett WL, Odelola OA, Wilson LM, et al. Evaluation of guideline recommendations on oral medications for type 2 diabetes mellitus: a systematic review. Ann Intern Med. 2012;156(1, pt 1):27-36.
Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15(6):540-559. 6. Raebel MA, Ellis JL, Schroeder EB, et al. Intensification of antihyperglycemic therapy among patients with incident diabetes: a Surveillance Prevention and Management of Diabetes Mellitus (SUPREME-DM) study. Pharmacoepidemiol Drug Saf. 2014;23(7):699-710. 7. Raebel MA, Xu S, Goodrich GK, et al. Initial antihyperglycemic drug therapy among 241 327 adults with newly identified diabetes from 2005 through 2010: a Surveillance, Prevention, and Management of Diabetes Mellitus (SUPREME-DM) study. Ann Pharmacother. 2013;47(10):1280-1291.
5. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical
jamainternalmedicine.com
JAMA Internal Medicine December 2014 Volume 174, Number 12
Copyright 2014 American Medical Association. All rights reserved.
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1963
