Clinical Predictors of the Need for Further Treatment Escalation in Patients with Type 2 Diabetes on Basal Insulin Therapy – A Retrospective Observational Study

Christina Buchholz; Melanie Kahle-Stephan; Juris J. Meier; Michael A. Nauck

doi:10.1055/a-0972-9700

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2019; 127(10): 663-671
DOI: 10.1055/a-0972-9700

Article

Clinical Predictors of the Need for Further Treatment Escalation in Patients with Type 2 Diabetes on Basal Insulin Therapy – A Retrospective Observational Study

Authors

Christina Buchholz

¹Diabetes Center Bad Lauterberg, Bad Lauterberg, Germany
Melanie Kahle-Stephan

¹Diabetes Center Bad Lauterberg, Bad Lauterberg, Germany

²Diabetes Center Bochum-Hattingen, Medical Department I, St. Josef-Hospital (Ruhr-University Bochum), Bochum, Germany
Juris J. Meier

²Diabetes Center Bochum-Hattingen, Medical Department I, St. Josef-Hospital (Ruhr-University Bochum), Bochum, Germany
Michael A. Nauck

¹Diabetes Center Bad Lauterberg, Bad Lauterberg, Germany

²Diabetes Center Bochum-Hattingen, Medical Department I, St. Josef-Hospital (Ruhr-University Bochum), Bochum, Germany

Abstract

Background/Aims The aim of this study was to identify clinical characteristics that distinguish patients who achieve sufficient glycaemic control with basal insulin and oral glucose-lowering medications from those who need treatment intensification.

Patients/Methods 213 out of 1 042 consecutively hospitalized type 2-diabetic patients were treated with basal insulin/oral agents. After titration to fasting glucose target, in 156 patients (73.2%) continuation of basal insulin treatment was recommended, while in 57 (26.8%), intensification of treatment was necessary. We compared patients’ characteristics and plasma glucose profiles between these groups.

Results Patients needing intensified regimens (basal-bolus regimes, premixed insulin ;GLP-1 receptor agonists) had higher initial HbA_1c values (87±17 mmol/mol [10.1±1.7%] vs. 80±19 mmol/mol [9.5±1.9%], p=0.028), were more likely to be female (49.1 vs. 25.0%, p=0.0014) and more obese, and required higher basal insulin doses (62±40 vs. 39±27 IU/d, p<0.0001). In both patient groups, basal insulin reduced fasting plasma glucose into the target range (6.6±1.3 vs. 5.7±0.8 mmol/l), however, in those needing treatment intensification, post-breakfast plasma glucose remained substantially higher after basal insulin titration (12.6±2.0 vs.9.4±1.6 mmol/l, p<0.0001). Before hospital discharge, similar plasma glucose profiles were reached in both groups.

Conclusions Basal insulin therapy can provide satisfactory glucose control in more than 70% of patients with type 2 diabetes. Long diabetes duration, obesity, insulin resistance and female sex indicate a need for further treatment intensification.

Key words

basal insulin - fasting plasma glucose - plasma glucose profiles - post-prandial plasma glucose - titration

Full Text

References

References
1 Riddle MC, Rosenstock J, Gerich J. et al. 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: 3080-3086
2 Yki-Järvinen H, Kauppinen-Makelin R, Tiikkainen M. et al. Insulin glargine or NPH combined with metformin in type 2 diabetes: The LANMET study. Diabetologia 2006; 49: 442-451
3 Yki-Järvinen H, Ryysy L, Nikkila K. et al. Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial. Annals of Internal Medicine 1999; 130: 389-396
4 Fritsche A, Larbig M, Owens D. et al. Comparison between a basal-bolus and a premixed insulin regimen in individuals with type 2 diabetes-results of the GINGER study. Diabetes Obes Metab 2010; 12: 115-123. doi:10.1111/j.1463-1326.2009.01165.x
5 Mosenzon O, Raz I. Intensification of insulin therapy for type 2 diabetic patients in primary care: Basal-bolus regimen versus premix insulin analogs: When and for whom?. Diabetes Care 2013; 36 (Suppl. 2) S212-S218. doi:10.2337/dcS13-2007
6 Vora J, Cohen N, Evans M. et al. Intensifying insulin regimen after basal insulin optimization in adults with type 2 diabetes: A 24-week, randomized, open-label trial comparing insulin glargine plus insulin glulisine with biphasic insulin aspart (LanScape). Diabetes Obes Metab 2015; 17: 1133-1141. doi:10.1111/dom.12528
7 Janka HU, Plewe G, Riddle MC. et al. Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes. Diabetes Care 2005; 28: 254-259
8 Aschner P, Sethi B, Gomez-Peralta F. et al. Insulin glargine compared with premixed insulin for management of insulin-naive type 2 diabetes patients uncontrolled on oral antidiabetic drugs: The open-label, randomized GALAPAGOS study. J Diabetes Complications 2015; 29: 838-845. doi:10.1016/j.jdiacomp.2015.04.003
9 Holman RR, Farmer AJ, Davies MJ. et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med 2009; 361: 1736-1747. doi:10.1056/NEJMoa0905479
10 Abrahamson MJ, Peters A. Intensification of insulin therapy in patients with type 2 diabetes mellitus: An algorithm for basal-bolus therapy. Ann Med 2012; 44: 836-846. doi:10.3109/07853890.2012.699715
11 Giugliano D, Chiodini P, Maiorino MI. et al. Intensification of insulin therapy with basal-bolus or premixed insulin regimens in type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Endocrine 2016; 51: 417-428. doi:10.1007/s12020-015-0718-3
12 Rosenstock J, Ahmann AJ, Colon G. et al. Advancing insulin therapy in type 2 diabetes previously treated with glargine plus oral agents: Prandial premixed (insulin lispro protamine suspension/lispro) versus basal/bolus (glargine/lispro) therapy. Diabetes Care 2008; 31: 20-25. doi:10.2337/dc07-1122
13 Eng C, Kramer CK, Zinman B. et al. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: A systematic review and meta-analysis. Lancet 2014; 384: 2228-2234. doi:10.1016/S0140-6736(14)61335-0
14 Wysham CH, Lin J, Kuritzky L. Safety and efficacy of a glucagon-like peptide-1 receptor agonist added to basal insulin therapy versus basal insulin with or without a rapid-acting insulin in patients with type 2 diabetes: Results of a meta-analysis. Postgrad Med 2017; 129: 436-445. doi:10.1080/00325481.2017.1297669
15 Yki-Järvinen H, Bergenstal R, Ziemen M. et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: Glucose control and hypoglycemia in a 6-month randomized controlled trial Edition 2. Diabetes Care 2014; 37: 3235-3243. doi:10.2337/dc14-0990
16 Diamant M, Nauck MA, Shaginian R. et al. Glucagon-like Peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes care 2014; 37: 2763-2773. doi:10.2337/dc14-0876
17 Nathan DM, Turgeon H, Regan S. Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia 2007; 50: 2239-2244. doi:10.1007/s00125-007-0803-0
18 Schleicher E. Average blood glucose instead of HbA1c? Original German title: Neuer Parameter fur die Stoffwechseleinstellung. Durchschnittsglukose statt HbA1c?. MMW Fortschr Med 2009; 151: 45-47
19 Manley SE. Estimated average glucose derived from HbA1c eAG: report from European Association for the Study of Diabetes (EASD), Amsterdam 2007. Diabet Med 2008; 25: 126-128. doi:10.1111/j.1464-5491.2008.02383.x
20 Inzucchi SE, Bergenstal RM, Buse JB. et al. Management of hyperglycaemia in type 2 diabetes: A patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2012; 55: 1577-15596. doi:10.1007/s00125-012-2534-0
21 Davies MJ, D'Alessio DA, Fradkin J. et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2018; 61: 2461-2498. doi:10.1007/s00125-018-4729-5
22 Holman RR, Thorne KI, Farmer AJ. et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med 2007; 357: 1716-1730. doi:10.1056/NEJMoa075392
23 Rosenstock J, Davies M, Home PD. et al. A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetologia 2008; 51: 408-416. doi:10.1007/s00125-007-0911-x
24 Zinman B, Philis-Tsimikas A, Cariou B. et al. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: A 1-year, randomized, treat-to-target trial (BEGIN Once Long). Diabetes Care 2012; 35: 2464-2471. doi:10.2337/dc12-1205
25 Mata-Cases M, Mauricio D, Franch-Nadal J. Clinical characteristics of type 2 diabetic patients on basal insulin therapy with adequate fasting glucose control who do not achieve HbA1c targets. J Diabetes 2017; 9: 34-44. doi:10.1111/1753-0407.12373
26 Raccah D, Chou E, Colagiuri S. et al. A global study of the unmet need for glycemic control and predictor factors among patients with type 2 diabetes mellitus who have achieved optimal fasting plasma glucose control on basal insulin. Diabetes Metab Res Rev 2017; 33: e2858.h doi:10.1002/dmrr.2858
27 Meier JJ, Pennartz C, Schenker N. et al. Hyperglycaemia is associated with impaired pulsatile insulin secretion: Effect of basal insulin therapy. Diabetes, obesity & metabolism 2013; 15: 258-263. doi:10.1111/dom.12022
28 Menge BA, Gruber L, Jorgensen SM. et al. Loss of inverse relationship between pulsatile insulin and glucagon secretion in patients with type 2 diabetes. Diabetes 2011; 60: 2160-2168. doi:10.2337/db11-0251
29 Matsuda M, DeFronzo RA, Glass L. et al. Glucagon dose-response curve for hepatic glucose production and glucose disposal in type 2 diabetic patients and normal individuals. Metabolism 2002; 51: 1111-1119
30 Liljenquist JE, Mueller GL, Cherrington AD. et al. Evidence for an important role of glucagon in the regulation of hepatic glucose production in normal man. J Clin Invest 1977; 59: 369-374. doi:10.1172/JCI108649
31 Mathieu C, Shankar RR, Lorber D. et al. A randomized clinical trial to evaluate the efficacy and safety of co-administration of sitagliptin with intensively titrated insulin glargine. Diabetes Ther 2015; 6: 127-142. doi:10.1007/s13300-015-0105-3
32 Hernandez AF, Green JB, Janmohamed S. et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 2018; 392: 1519-1529. doi:10.1016/S0140-6736(18)32261-X
33 Marso SP, Bain SC, Consoli A. et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016; 375: 1834-1844. doi:10.1056/NEJMoa1607141
34 Marso SP, Daniels GH, Brown-Frandsen K. et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375: 311-322. doi:10.1056/NEJMoa1603827
35 Neal B, Perkovic V, Mahaffey KW. et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 644-657. doi:10.1056/NEJMoa1611925
36 Wiviott SD, Raz I, Bonaca MP. et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380: 347-357. doi:10.1056/NEJMoa1812389
37 Zinman B, Wanner C, Lachin JM. et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117-2128. doi:10.1056/NEJMoa1504720
38 UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-865
39 Holman RR, Paul SK, Bethel MA. et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359: 1577-1589. doi:10.1056/NEJMoa0806470

Supplementary Material

Supplementary Material (PDF)