Skip to main content
Top
Published in: Diabetes Therapy 6/2018

Open Access 01-12-2018 | Original Research

Retrospective Cohort Analysis of the Reduced Burden of Hypoglycemia Associated with Dipeptidyl Peptidase-4 Inhibitor Use in Patients with Type 2 Diabetes Mellitus

Authors: Yuexin Tang, Jinan Liu, Hakima Hannachi, Samuel S. Engel, Michael L. Ganz, Swapnil Rajpathak

Published in: Diabetes Therapy | Issue 6/2018

Login to get access

Abstract

Introduction

The use of antihyperglycemic agents (AHA), especially insulin and sulfonylureas (SU), is a risk factor for hypoglycemia. Despite the significant clinical and economic burdens associated with hypoglycemia and the decreasing use of SU in favor of other oral AHA, relatively little is known about hypoglycemia trends specific to the use of non-insulin AHA. We sought to estimate annual hypoglycemia event rates and costs among patients with type 2 diabetes mellitus (T2DM) who started either SU or dipeptidyl peptidase-4 inhibitors (DPP-4i) and to predict rates and costs in the absence of DPP-4i.

Methods

Truven’s MarketScan Commercial Claims database was used to estimate hypoglycemia event rates and costs from 2007 to 2013. Hypoglycemia, defined using diagnosis codes, was assessed during the 12 months following SU (n = 245,201) or DPP-4i (n = 176,786) initiation by adults with T2DM. Coefficients from a Poisson regression model used to estimate the impact of patient characteristics on hypoglycemia rates for patients who started SU were used to predict rates for patients who started DPP-4i had they started SU instead.

Results

Hypoglycemia events per 100 patient-years (costs per event) ranged from 5.4 ($565) in 2007 to 10.4 ($1154) in 2013 for patients starting SU; rates (costs) for patients starting DPP-4i ranged from 3.2 ($308) in 2007 to 6.4 ($482) in 2013. Predicted hypoglycemia rates would have been 5.3–9.9 per 100 person-years for patients who started DPP-4i had they started SU instead. Starting DPP-4i, rather than SU, would have resulted in national savings of $750.3 million in healthcare costs due to avoided hypoglycemia events during this period.

Conclusions

Hypoglycemia rates and costs were consistently higher for patients who started SU rather than DPP-4i. The overall burden of hypoglycemia could be lowered substantially in the USA if, when feasible, patients with T2DM initiate DPP-4i instead of SU.

Funding

Merck & Co., Inc., Kenilworth, NJ USA.
Appendix
Available only for authorised users
Literature
2.
go back to reference Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14.CrossRef Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14.CrossRef
3.
go back to reference American Diabetes A. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;36(4):1033–46.CrossRef American Diabetes A. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;36(4):1033–46.CrossRef
4.
go back to reference American Diabetes Association. Glycemic targets. Sec. 6 in standards of medical care in diabetes—2015. Diabetes Care. 2015;38(Suppl 1):S33–40.CrossRef American Diabetes Association. Glycemic targets. Sec. 6 in standards of medical care in diabetes—2015. Diabetes Care. 2015;38(Suppl 1):S33–40.CrossRef
5.
go back to reference Garcia-Perez LE, Alvarez M, Dilla T, Gil-Guillen V, Orozco-Beltran D. Adherence to therapies in patients with type 2 diabetes. Diabetes Ther. 2013;4(2):175–94.CrossRef Garcia-Perez LE, Alvarez M, Dilla T, Gil-Guillen V, Orozco-Beltran D. Adherence to therapies in patients with type 2 diabetes. Diabetes Ther. 2013;4(2):175–94.CrossRef
6.
go back to reference Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case–control analysis. Diabetes Care. 2008;31(11):2086–91.CrossRef Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case–control analysis. Diabetes Care. 2008;31(11):2086–91.CrossRef
7.
go back to reference Cryer PE. Glycemic goals in diabetes: trade-off between glycemic control and iatrogenic hypoglycemia. Diabetes. 2014;63(7):2188–95.CrossRef Cryer PE. Glycemic goals in diabetes: trade-off between glycemic control and iatrogenic hypoglycemia. Diabetes. 2014;63(7):2188–95.CrossRef
8.
go back to reference Curkendall S, Zhang B, Oh K, Williams S, Pollack M, Graham J. Incidence and cost of hypoglycemia among patients with type 2 diabetes in the United States: analysis of a health insurance database. J Clin Outcomes Manag. 2011;18(10):455–62. Curkendall S, Zhang B, Oh K, Williams S, Pollack M, Graham J. Incidence and cost of hypoglycemia among patients with type 2 diabetes in the United States: analysis of a health insurance database. J Clin Outcomes Manag. 2011;18(10):455–62.
9.
go back to reference Karter AJ, Warton EM, Lipska KJ, et al. Development and validation of a tool to identify patients with type 2 diabetes at high risk of hypoglycemia-related emergency department or hospital use. JAMA Intern Med. 2017;177(10):1461–70.CrossRef Karter AJ, Warton EM, Lipska KJ, et al. Development and validation of a tool to identify patients with type 2 diabetes at high risk of hypoglycemia-related emergency department or hospital use. JAMA Intern Med. 2017;177(10):1461–70.CrossRef
10.
go back to reference Roumie CL, Min JY, Greevy RA, et al. Risk of hypoglycemia following intensification of metformin treatment with insulin versus sulfonylurea. CMAJ. 2016;188(6):E104–12.CrossRef Roumie CL, Min JY, Greevy RA, et al. Risk of hypoglycemia following intensification of metformin treatment with insulin versus sulfonylurea. CMAJ. 2016;188(6):E104–12.CrossRef
11.
go back to reference Simon D, de Pablos-Velasco P, Parhofer KG, et al. Hypoglycaemic episodes in patients with type 2 diabetes–risk factors and associations with patient-reported outcomes: the PANORAMA Study. Diabetes Metab. 2015;41(6):470–9.CrossRef Simon D, de Pablos-Velasco P, Parhofer KG, et al. Hypoglycaemic episodes in patients with type 2 diabetes–risk factors and associations with patient-reported outcomes: the PANORAMA Study. Diabetes Metab. 2015;41(6):470–9.CrossRef
12.
go back to reference Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ. 2010;340:b4909.CrossRef Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ. 2010;340:b4909.CrossRef
13.
go back to reference Hsu PF, Sung SH, Cheng HM, et al. Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study. Diabetes Care. 2013;36(4):894–900.CrossRef Hsu PF, Sung SH, Cheng HM, et al. Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study. Diabetes Care. 2013;36(4):894–900.CrossRef
14.
go back to reference Johnston SS, Conner C, Aagren M, Ruiz K, Bouchard J. Association between hypoglycaemic events and fall-related fractures in Medicare-covered patients with type 2 diabetes. Diabetes Obes Metab. 2012;14(7):634–43.CrossRef Johnston SS, Conner C, Aagren M, Ruiz K, Bouchard J. Association between hypoglycaemic events and fall-related fractures in Medicare-covered patients with type 2 diabetes. Diabetes Obes Metab. 2012;14(7):634–43.CrossRef
15.
go back to reference Johnston SS, Conner C, Aagren M, Smith DM, Bouchard J, Brett J. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care. 2011;34(5):1164–70.CrossRef Johnston SS, Conner C, Aagren M, Smith DM, Bouchard J, Brett J. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care. 2011;34(5):1164–70.CrossRef
16.
go back to reference McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012;35(9):1897–901.CrossRef McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012;35(9):1897–901.CrossRef
17.
go back to reference Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010;363(15):1410–8.CrossRef Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010;363(15):1410–8.CrossRef
18.
go back to reference Quilliam BJ, Simeone JC, Ozbay AB, Kogut SJ. The incidence and costs of hypoglycemia in type 2 diabetes. Am J Manag Care. 2011;17(10):673–80.PubMed Quilliam BJ, Simeone JC, Ozbay AB, Kogut SJ. The incidence and costs of hypoglycemia in type 2 diabetes. Am J Manag Care. 2011;17(10):673–80.PubMed
19.
go back to reference Candrilli SD, Meyers JL, Boye K, Bae JP. Health care resource utilization and costs during episodes of care for type 2 diabetes mellitus-related comorbidities. J Diabetes Complicat. 2015;29(4):529–33.CrossRef Candrilli SD, Meyers JL, Boye K, Bae JP. Health care resource utilization and costs during episodes of care for type 2 diabetes mellitus-related comorbidities. J Diabetes Complicat. 2015;29(4):529–33.CrossRef
20.
go back to reference Brod M, Rana A, Barnett AH. Impact of self-treated hypoglycaemia in type 2 diabetes: a multinational survey in patients and physicians. Curr Med Res Opin. 2012;28(12):1947–58.CrossRef Brod M, Rana A, Barnett AH. Impact of self-treated hypoglycaemia in type 2 diabetes: a multinational survey in patients and physicians. Curr Med Res Opin. 2012;28(12):1947–58.CrossRef
21.
go back to reference Fidler C, Elmelund Christensen T, Gillard S. Hypoglycemia: an overview of fear of hypoglycemia, quality-of-life, and impact on costs. J Med Econ. 2011;14(5):646–55.CrossRef Fidler C, Elmelund Christensen T, Gillard S. Hypoglycemia: an overview of fear of hypoglycemia, quality-of-life, and impact on costs. J Med Econ. 2011;14(5):646–55.CrossRef
22.
go back to reference International Hypoglycaemia Study Group. Minimizing hypoglycemia in diabetes. Diabetes Care. 2015;38(8):1583–91.CrossRef International Hypoglycaemia Study Group. Minimizing hypoglycemia in diabetes. Diabetes Care. 2015;38(8):1583–91.CrossRef
23.
go back to reference Wild D, von Maltzahn R, Brohan E, Christensen T, Clauson P, Gonder-Frederick L. A critical review of the literature on fear of hypoglycemia in diabetes: implications for diabetes management and patient education. Patient Educ Couns. 2007;68(1):10–5.CrossRef Wild D, von Maltzahn R, Brohan E, Christensen T, Clauson P, Gonder-Frederick L. A critical review of the literature on fear of hypoglycemia in diabetes: implications for diabetes management and patient education. Patient Educ Couns. 2007;68(1):10–5.CrossRef
24.
go back to reference Lipska KJ, Yao X, Herrin J, et al. Trends in drug utilization, glycemic control, and rates of severe hypoglycemia, 2006–2013. Diabetes Care. 2017;40(4):468–75.CrossRef Lipska KJ, Yao X, Herrin J, et al. Trends in drug utilization, glycemic control, and rates of severe hypoglycemia, 2006–2013. Diabetes Care. 2017;40(4):468–75.CrossRef
25.
go back to reference Ahren B. Are sulfonylureas less desirable than DPP-4 inhibitors as add-on to metformin in the treatment of type 2 diabetes? Curr Diab Rep. 2011;11(2):83–90.CrossRef Ahren B. Are sulfonylureas less desirable than DPP-4 inhibitors as add-on to metformin in the treatment of type 2 diabetes? Curr Diab Rep. 2011;11(2):83–90.CrossRef
26.
go back to reference Detournay B, Halimi S, Robert J, Deschaseaux C, Dejager S. Hypoglycemia hospitalization frequency in patients with type 2 diabetes mellitus: a comparison of dipeptidyl peptidase 4 inhibitors and insulin secretagogues using the French health insurance database. Vasc Health Risk Manag. 2015;11:417–25.PubMedPubMedCentral Detournay B, Halimi S, Robert J, Deschaseaux C, Dejager S. Hypoglycemia hospitalization frequency in patients with type 2 diabetes mellitus: a comparison of dipeptidyl peptidase 4 inhibitors and insulin secretagogues using the French health insurance database. Vasc Health Risk Manag. 2015;11:417–25.PubMedPubMedCentral
27.
go back to reference Raju A, Shetty S, Cai B, D’Souza AO. Hypoglycemia incidence rates and associated health care costs in patients with type 2 diabetes mellitus treated with second-line linagliptin or sulfonylurea after metformin monotherapy. J Manag Care Spec Pharm. 2016;22(5):483–92.PubMed Raju A, Shetty S, Cai B, D’Souza AO. Hypoglycemia incidence rates and associated health care costs in patients with type 2 diabetes mellitus treated with second-line linagliptin or sulfonylurea after metformin monotherapy. J Manag Care Spec Pharm. 2016;22(5):483–92.PubMed
28.
go back to reference Turner LW, Nartey D, Stafford RS, Singh S, Alexander GC. Ambulatory treatment of type 2 diabetes in the U.S., 1997–2012. Diabetes Care. 2014;37(4):985–92.CrossRef Turner LW, Nartey D, Stafford RS, Singh S, Alexander GC. Ambulatory treatment of type 2 diabetes in the U.S., 1997–2012. Diabetes Care. 2014;37(4):985–92.CrossRef
29.
go back to reference Quan H, Sundararajan V, Halfon P, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43(11):1130–9.CrossRef Quan H, Sundararajan V, Halfon P, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43(11):1130–9.CrossRef
30.
go back to reference Ginde AA, Blanc PG, Lieberman RM, Camargo CA Jr. Validation of ICD-9-CM coding algorithm for improved identification of hypoglycemia visits. BMC Endocr Disord. 2008;8:4.CrossRef Ginde AA, Blanc PG, Lieberman RM, Camargo CA Jr. Validation of ICD-9-CM coding algorithm for improved identification of hypoglycemia visits. BMC Endocr Disord. 2008;8:4.CrossRef
31.
go back to reference Lipska KJ, Ross JS, Wang Y, et al. National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011. JAMA Intern Med. 2014;174(7):1116–24.CrossRef Lipska KJ, Ross JS, Wang Y, et al. National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011. JAMA Intern Med. 2014;174(7):1116–24.CrossRef
32.
go back to reference Wang J, Geiss L, Williams D, Gregg E. Trends in emergency department visit rates for hypoglycemia and hyperglycemic crisis among adults with diabetes, United States, 2006–2011. PLoS One. 2015;10(8):e0134917.CrossRef Wang J, Geiss L, Williams D, Gregg E. Trends in emergency department visit rates for hypoglycemia and hyperglycemic crisis among adults with diabetes, United States, 2006–2011. PLoS One. 2015;10(8):e0134917.CrossRef
33.
go back to reference Zhao Y, Shi Q, Wang Y, Fonseca V, Shi L. Economic burden of hypoglycemia: utilization of emergency department and outpatient services in the United States (2005–2009). J Med Econ. 2016;19(9):852–7.CrossRef Zhao Y, Shi Q, Wang Y, Fonseca V, Shi L. Economic burden of hypoglycemia: utilization of emergency department and outpatient services in the United States (2005–2009). J Med Econ. 2016;19(9):852–7.CrossRef
34.
go back to reference Pathak RD, Schroeder EB, Seaquist ER, et al. Severe hypoglycemia requiring medical intervention in a large cohort of adults with diabetes receiving care in U.S. integrated health care delivery systems: 2005–2011. Diabetes Care. 2016;39(3):363–70.CrossRef Pathak RD, Schroeder EB, Seaquist ER, et al. Severe hypoglycemia requiring medical intervention in a large cohort of adults with diabetes receiving care in U.S. integrated health care delivery systems: 2005–2011. Diabetes Care. 2016;39(3):363–70.CrossRef
35.
go back to reference Edridge CL, Dunkley AJ, Bodicoat DH, et al. Prevalence and incidence of hypoglycaemia in 532,542 people with type 2 diabetes on oral therapies and insulin: a systematic review and meta-analysis of population based studies. PLoS One. 2015;10(6):e0126427.CrossRef Edridge CL, Dunkley AJ, Bodicoat DH, et al. Prevalence and incidence of hypoglycaemia in 532,542 people with type 2 diabetes on oral therapies and insulin: a systematic review and meta-analysis of population based studies. PLoS One. 2015;10(6):e0126427.CrossRef
36.
go back to reference Mishriky BM, Cummings DM, Tanenberg RJ. The efficacy and safety of DPP4 inhibitors compared to sulfonylureas as add-on therapy to metformin in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2015;109(2):378–88.CrossRef Mishriky BM, Cummings DM, Tanenberg RJ. The efficacy and safety of DPP4 inhibitors compared to sulfonylureas as add-on therapy to metformin in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2015;109(2):378–88.CrossRef
37.
go back to reference Mearns ES, Sobieraj DM, White CM, et al. Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis. PLoS One. 2015;10(4):e0125879.CrossRef Mearns ES, Sobieraj DM, White CM, et al. Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis. PLoS One. 2015;10(4):e0125879.CrossRef
39.
go back to reference Jakubczyk M, Rdzanek E, Niewada M, Czech M. Economic resources consumption structure in severe hypoglycemia episodes: a systematic review and meta-analysis. Expert Rev Pharmacoecon Outcomes Res. 2015;15(5):813–22.CrossRef Jakubczyk M, Rdzanek E, Niewada M, Czech M. Economic resources consumption structure in severe hypoglycemia episodes: a systematic review and meta-analysis. Expert Rev Pharmacoecon Outcomes Res. 2015;15(5):813–22.CrossRef
40.
go back to reference Veronese G, Marchesini G, Forlani G, Fabbri A, Italian Society of Emergency Medicine (SIMEU). Are severe hypoglycemic episodes in diabetes correctly identified by administrative data? Evidence of underreporting from the HYPOTHESIS study. Acta Diabetol. 2016;53(4):677–80.CrossRef Veronese G, Marchesini G, Forlani G, Fabbri A, Italian Society of Emergency Medicine (SIMEU). Are severe hypoglycemic episodes in diabetes correctly identified by administrative data? Evidence of underreporting from the HYPOTHESIS study. Acta Diabetol. 2016;53(4):677–80.CrossRef
Metadata
Title
Retrospective Cohort Analysis of the Reduced Burden of Hypoglycemia Associated with Dipeptidyl Peptidase-4 Inhibitor Use in Patients with Type 2 Diabetes Mellitus
Authors
Yuexin Tang
Jinan Liu
Hakima Hannachi
Samuel S. Engel
Michael L. Ganz
Swapnil Rajpathak
Publication date
01-12-2018
Publisher
Springer Healthcare
Published in
Diabetes Therapy / Issue 6/2018
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI
https://doi.org/10.1007/s13300-018-0512-3

Other articles of this Issue 6/2018

Diabetes Therapy 6/2018 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.