Skip to main content
Top
Published in: BMC Endocrine Disorders 1/2015

Open Access 01-12-2015 | Research article

Treatment intensification using long-acting insulin –predictors of future basal insulin supported oral therapy in the DIVE registry

Authors: Thomas Danne, Tobias Bluhmki, Jochen Seufert, Matthias Kaltheuner, Wolfgang Rathmann, Jan Beyersmann, Peter Bramlage, for the DIVE study group

Published in: BMC Endocrine Disorders | Issue 1/2015

Login to get access

Abstract

Background

In patients with type-2 diabetes receiving oral antidiabetic drugs (OADs), the addition of insulin is frequently required to achieve sufficient control over blood glucose levels. It is, however, difficult to predict if, when and in which patients insulin therapy will be needed. We aimed to identify patient related variables associated with the addition of basal insulin to oral therapy resulting in a basal supported oral therapy (BOT).

Methods

DIVE (DIabetes Versorgungs-Evaluation) is a prospective, observational, multi-centre diabetes registry established in Germany in 2011. For the present explorative analysis, 31,008 patients with type-2 diabetes prescribed at least one OAD were included. Patients who had previously received insulin and those over 90 years old were excluded. The event of interest was defined as the initiation of BOT during the observational period. Cause-specific Cox proportional hazards models based on a competing risk framework were applied for risk quantification.

Results

Multivariable adjusted hazard ratios demonstrated that longer diabetes duration, higher BMI, poorer glycaemic control, documentation of any micro- or macrovascular comorbidity, the presence of concomitant non-antidiabetic pharmacotherapies, and greater numbers of prescribed OADs increased the likelihood of BOT initiation. On the other hand BOT initiation was less likely in patients with older age and female gender. Analysing the likelihood of OAD termination without initiation of BOT provided supportive evidence for the variables predictive of BOT initiation.

Discussion

Analysis of the DIVE registry has resulted in the identification of a number of factors that may be predictive for the initiation of BOT for type-2 diabetes patients initially prescribed one or more OADs. Poor glycaemic control, the presence of vascular comorbidities and concomitant medications, and a greater number of OADs were all detected to increase the risk of a switch to BOT. Female gender and younger age showed protective properties.

Conclusions

The close monitoring of patients displaying these characteristics may help to identify individuals who might benefit from early addition of insulin therapy to their oral treatment regimen.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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(21):2005–12.CrossRefPubMed 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(21):2005–12.CrossRefPubMed
2.
go back to reference Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al. 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(1):193–203.CrossRefPubMedPubMedCentral Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al. 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(1):193–203.CrossRefPubMedPubMedCentral
3.
go back to reference American Diabetes Association. Executive summary: standards of medical care in diabetes--2014. Diabetes Care. 2014;37 Suppl 1:S5–13. American Diabetes Association. Executive summary: standards of medical care in diabetes--2014. Diabetes Care. 2014;37 Suppl 1:S5–13.
4.
go back to reference Home P, Riddle M, Cefalu WT, Bailey CJ, Bretzel RG, Del Prato S, et al. Insulin therapy in people with type 2 diabetes: opportunities and challenges? Diabetes Care. 2014;37(6):1499–508.CrossRefPubMed Home P, Riddle M, Cefalu WT, Bailey CJ, Bretzel RG, Del Prato S, et al. Insulin therapy in people with type 2 diabetes: opportunities and challenges? Diabetes Care. 2014;37(6):1499–508.CrossRefPubMed
5.
go back to reference Matthaei S, Bierwirth R, Fritsche A, Gallwitz B, Haring HU, Joost HG, et al. Medical antihyperglycaemic treatment of type 2 diabetes mellitus: update of the evidence-based guideline of the German Diabetes Association. Exp Clin Endocrinol Diabetes. 2009;117(9):522–57.CrossRefPubMed Matthaei S, Bierwirth R, Fritsche A, Gallwitz B, Haring HU, Joost HG, et al. Medical antihyperglycaemic treatment of type 2 diabetes mellitus: update of the evidence-based guideline of the German Diabetes Association. Exp Clin Endocrinol Diabetes. 2009;117(9):522–57.CrossRefPubMed
6.
go back to reference Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26(11):3080–6.CrossRefPubMed Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26(11):3080–6.CrossRefPubMed
7.
go back to reference Hermansen K, Davies M, Derezinski T, Martinez Ravn G, Clauson P, Home P. 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-naive people with type 2 diabetes. Diabetes Care. 2006;29(6):1269–74.CrossRefPubMed Hermansen K, Davies M, Derezinski T, Martinez Ravn G, Clauson P, Home P. 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-naive people with type 2 diabetes. Diabetes Care. 2006;29(6):1269–74.CrossRefPubMed
8.
go back to reference Goudswaard AN, Furlong NJ, Rutten GE, Stolk RP, Valk GD. Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004;4, CD003418.PubMed Goudswaard AN, Furlong NJ, Rutten GE, Stolk RP, Valk GD. Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004;4, CD003418.PubMed
9.
go back to reference Holman RR, Thorne KI, Farmer AJ, Davies MJ, Keenan JF, Paul S, et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med. 2007;357(17):1716–30.CrossRefPubMed Holman RR, Thorne KI, Farmer AJ, Davies MJ, Keenan JF, Paul S, et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med. 2007;357(17):1716–30.CrossRefPubMed
10.
go back to reference Edelman S, Pettus J. Challenges associated with insulin therapy in type 2 diabetes mellitus. Am J Med. 2014;127(10 Suppl):S11–6.CrossRefPubMed Edelman S, Pettus J. Challenges associated with insulin therapy in type 2 diabetes mellitus. Am J Med. 2014;127(10 Suppl):S11–6.CrossRefPubMed
11.
go back to reference Larkin ME, Capasso VA, Chen CL, Mahoney EK, Hazard B, Cagliero E, et al. Measuring psychological insulin resistance: barriers to insulin use. Diabetes Educ. 2008;34(3):511–7.CrossRefPubMed Larkin ME, Capasso VA, Chen CL, Mahoney EK, Hazard B, Cagliero E, et al. Measuring psychological insulin resistance: barriers to insulin use. Diabetes Educ. 2008;34(3):511–7.CrossRefPubMed
12.
go back to reference Peyrot M, Rubin RR, Lauritzen T, Skovlund SE, Snoek FJ, Matthews DR, et al. 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):2673–9.CrossRefPubMed Peyrot M, Rubin RR, Lauritzen T, Skovlund SE, Snoek FJ, Matthews DR, et al. 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):2673–9.CrossRefPubMed
13.
go back to reference Kostev K, Dippel FW. Predictors for the initiation of a basal supported oral therapy (BOT) in type 2 diabetic patients under real-life conditions in Germany. Prim Care Diabetes. 2012;6(4):329–35.CrossRefPubMed Kostev K, Dippel FW. Predictors for the initiation of a basal supported oral therapy (BOT) in type 2 diabetic patients under real-life conditions in Germany. Prim Care Diabetes. 2012;6(4):329–35.CrossRefPubMed
14.
go back to reference Danne T, Kaltheuner M, Koch A, Ernst S, Rathmann W, Russmann HJ, et al. [“DIabetes Versorgungs-Evaluation” (DIVE)--a national quality assurance initiative at physicians providing care for patients with diabetes]. Dtsch Med Wochenschr. 2013;138(18):934–9.CrossRefPubMed Danne T, Kaltheuner M, Koch A, Ernst S, Rathmann W, Russmann HJ, et al. [“DIabetes Versorgungs-Evaluation” (DIVE)--a national quality assurance initiative at physicians providing care for patients with diabetes]. Dtsch Med Wochenschr. 2013;138(18):934–9.CrossRefPubMed
15.
go back to reference Hoelzel W, Weykamp C, Jeppsson JO, Miedema K, Barr JR, Goodall I, et al. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem. 2004;50(1):166–74.CrossRefPubMed Hoelzel W, Weykamp C, Jeppsson JO, Miedema K, Barr JR, Goodall I, et al. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem. 2004;50(1):166–74.CrossRefPubMed
16.
go back to reference van Buuren S. Multiple imputation of discrete and continuous data by fully conditional specification. Stat Methods Med Res. 2007;16(3):219–42.CrossRefPubMed van Buuren S. Multiple imputation of discrete and continuous data by fully conditional specification. Stat Methods Med Res. 2007;16(3):219–42.CrossRefPubMed
17.
go back to reference Su Y-S, Gelman A, Hill J, Yajima M. Multiple imputation with diagnostics (mi) in R: opening windows into the black Box. Journal of Statistical Software. 2011;45(2):1–31.CrossRef Su Y-S, Gelman A, Hill J, Yajima M. Multiple imputation with diagnostics (mi) in R: opening windows into the black Box. Journal of Statistical Software. 2011;45(2):1–31.CrossRef
18.
go back to reference Rubin DB. Multiple imputation for noneresponse in surveys. New York: J. Wiley & Sons; 1987.CrossRef Rubin DB. Multiple imputation for noneresponse in surveys. New York: J. Wiley & Sons; 1987.CrossRef
19.
go back to reference Spannagl M, Melzer N, Bramlage P, Englert C, Eisele R. Prospective, non-interventional study on the real-world use of certoparin in daily practice--the PROMEMBER study. Clin Appl Thromb Hemost. 2013;19(1):86–91.CrossRefPubMed Spannagl M, Melzer N, Bramlage P, Englert C, Eisele R. Prospective, non-interventional study on the real-world use of certoparin in daily practice--the PROMEMBER study. Clin Appl Thromb Hemost. 2013;19(1):86–91.CrossRefPubMed
20.
go back to reference Spoelstra JA, Stol RP, de Bruyne MC, Erkens JA, Herings RM, Leufkens HG, et al. Factors associated with switching from oral hypoglycaemic agents to insulin therapy. Neth J Med. 2002;60(6):243–8.PubMed Spoelstra JA, Stol RP, de Bruyne MC, Erkens JA, Herings RM, Leufkens HG, et al. Factors associated with switching from oral hypoglycaemic agents to insulin therapy. Neth J Med. 2002;60(6):243–8.PubMed
22.
go back to reference Vora J, Bain SC, Damci T, Dzida G, Hollander P, Meneghini LF, et al. Incretin-based therapy in combination with basal insulin: a promising tactic for the treatment of type 2 diabetes. Diabetes Metab. 2013;39(1):6–15.CrossRefPubMed Vora J, Bain SC, Damci T, Dzida G, Hollander P, Meneghini LF, et al. Incretin-based therapy in combination with basal insulin: a promising tactic for the treatment of type 2 diabetes. Diabetes Metab. 2013;39(1):6–15.CrossRefPubMed
23.
go back to reference Civera M, Merchante A, Salvador M, Sanz J, Martinez I. Safety and efficacy of repaglinide in combination with metformin and bedtime NPH insulin as an insulin treatment regimen in type 2 diabetes. Diabetes Res Clin Pract. 2008;79(1):42–7.CrossRefPubMed Civera M, Merchante A, Salvador M, Sanz J, Martinez I. Safety and efficacy of repaglinide in combination with metformin and bedtime NPH insulin as an insulin treatment regimen in type 2 diabetes. Diabetes Res Clin Pract. 2008;79(1):42–7.CrossRefPubMed
24.
go back to reference Allignol A, Schumacher M, Wanner C, Drechsler C, Beyersmann J. Understanding competing risks: a simulation point of view. BMC Med Res Methodol. 2011;11:86.CrossRefPubMedPubMedCentral Allignol A, Schumacher M, Wanner C, Drechsler C, Beyersmann J. Understanding competing risks: a simulation point of view. BMC Med Res Methodol. 2011;11:86.CrossRefPubMedPubMedCentral
Metadata
Title
Treatment intensification using long-acting insulin –predictors of future basal insulin supported oral therapy in the DIVE registry
Authors
Thomas Danne
Tobias Bluhmki
Jochen Seufert
Matthias Kaltheuner
Wolfgang Rathmann
Jan Beyersmann
Peter Bramlage
for the DIVE study group
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2015
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-015-0051-0

Other articles of this Issue 1/2015

BMC Endocrine Disorders 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
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.