Acta Diabetologica

, Volume 53, Issue 5, pp 717–726 | Cite as

Real-world therapeutic benefits of patients on insulin glargine versus NPH insulin

  • Albrecht Fiesselmann
  • Tobias Wiesner
  • Holger Fleischmann
  • Peter BramlageEmail author
Original Article



The addition of a single injection of insulin to the oral drugs (basal supported oral therapy; BOT) has been shown to greatly reduce blood glucose levels. The intermediate-acting NPH insulin (NPH) and the long-acting insulin glargine (Lantus®) have been compared for use in BOT in numerous clinical trials; however, their efficacy and safety in a real-life setting have not been described.


TIP (therapeutic benefits of patients on insulin glargine vs. NPH insulin being poorly controlled on prior short-time basal-insulin supported therapy with NPH insulin or insulin glargine) is a non-interventional, multicentre, observational study over 24 weeks. A total of 2629 patients were enrolled and 1931 were fully evaluable (1614 insulin glargine, 303 NPH insulin). Propensity scoring (PSM) was used to match 570 patients into 2 similar cohorts of 285 patients.


In the PSM cohort, a slightly greater reduction in FBG and HbA1c levels was seen in the insulin glargine group compared to the NPH group. A weight loss, which was slightly more pronounced in insulin glargine patients despite receiving a lower insulin dose relative to the NPH group, was seen in both the groups. Additionally, hypoglycaemia, including nocturnal and severe events, was more prevalent in the patients receiving BOT with NPH. The occurrence of new micro- or macro-vascular complications and adverse events was low for both groups. A large proportion of patients changed from NPH therapy to insulin glargine therapy during the study, which was mainly attributable to insufficient glucose modulation. Improvements in quality of life and treatment satisfaction were found for both types of insulin.


This observational study provides evidence from a real-life setting that BOT with insulin glargine provides slightly greater reductions in weight, FBG and HbA1c levels, with a lower risk of hypoglycaemia than patients receiving NPH. This conclusion indicates that insulin glargine may be preferable to NPH insulin for BOT.


Basal supported oral therapy Insulin Glargine Lantus® NPH Isophane 



The analysis was funded by Sanofi, Berlin, Germany.

Author contributions

HF designed the study. TW, AF, HF, and PB were involved in the analysis and interpretation of the data. PB drafted the first version of the manuscript, and all authors revised the article for important intellectual content. The final version was approved by all authors.

Compliance with ethical standards

Conflict of interest

TW and AF have attended advisory boards and received compensation from Sanofi Aventis Deutschland GmbH, Berlin, Germany. HF is an employee of Sanofi, Berlin, Germany. PB has received research funding and honoraria for consultancy from AstraZeneca, Bristol-Myers Squibb, Novartis, and Sanofi.

Ethical standard

The procedures in this study were in accordance with the ethical standards of the Declaration of Helsinki. The study protocol was approved by the ethics committee of the Berlin Chamber of Physicians. Furthermore the study was performed in accordance with the protocol, applicable local regulations and international guidelines.

Human and animal rights

All human rights were observed in keeping with the Declaration of Helsinki. There are no animal rights issues.

Informed consent

Written informed consent was obtained from all patients for being included in the study which has been done according to ethical standards and in keeping with the Declaration of Helsinki.


  1. 1.
    Turner RC et al (1999) 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 281(21):2005–2012CrossRefPubMedGoogle Scholar
  2. 2.
    American Diabetes, A (2016) 7. Approaches to glycemic treatment. Diabetes Care 39(Suppl 1):S52–S59Google Scholar
  3. 3.
    Matthaei S et al (2009) Medical antihyperglycaemic treatment of type 2 diabetes mellitus: update of the evidence-based guideline of the German Diabetes Association. Exp Clin Endocrinol Diabetes 117(9):522–557CrossRefPubMedGoogle Scholar
  4. 4.
    Home P et al (2014) Insulin therapy in people with type 2 diabetes: opportunities and challenges? Diabetes Care 37(6):1499–1508CrossRefPubMedGoogle Scholar
  5. 5.
    Holman RR et al (2007) Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med 357(17):1716–1730CrossRefPubMedGoogle Scholar
  6. 6.
    Rys P et al (2015) Systematic review and meta-analysis of randomized clinical trials comparing efficacy and safety outcomes of insulin glargine with NPH insulin, premixed insulin preparations or with insulin detemir in type 2 diabetes mellitus. Acta Diabetol 52(4):649–662CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Monami M et al (2016) Identification of predictors of response to basal insulin and DPP4 inhibitors in patients with type 2 diabetes failing to other therapies. Acta Diabetol 53(1):35–40CrossRefPubMedGoogle Scholar
  8. 8.
    Baxter MA (2008) The role of new basal insulin analogues in the initiation and optimisation of insulin therapy in type 2 diabetes. Acta Diabetol 45(4):253–268CrossRefPubMedGoogle Scholar
  9. 9.
    Yki-Jarvinen H et al (2000) Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group. Diabetes Care 23(8):1130–1136CrossRefPubMedGoogle Scholar
  10. 10.
    Yki-Jarvinen H (2002) Combination therapy with insulin and oral agents: optimizing glycemic control in patients with type 2 diabetes mellitus. Diabetes Metab Res Rev 18(Suppl 3):S77–S81CrossRefPubMedGoogle Scholar
  11. 11.
    Mullins P et al (2007) Negative binomial meta-regression analysis of combined glycosylated hemoglobin and hypoglycemia outcomes across eleven Phase III and IV studies of insulin glargine compared with neutral protamine Hagedorn insulin in type 1 and type 2 diabetes mellitus. Clin Ther 29(8):1607–1619CrossRefPubMedGoogle Scholar
  12. 12.
    Rosenstock J et al (2005) Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes. Diabetes Care 28(4):950–955CrossRefPubMedGoogle Scholar
  13. 13.
    Moock J et al (2010) Development and Testing of the Insulin Treatment Experience Questionnaire (ITEQ). Patient 3(1):45–58CrossRefPubMedGoogle Scholar
  14. 14.
    Massi Benedetti M et al (2003) A one-year, randomised, multicentre trial comparing insulin glargine with NPH insulin in combination with oral agents in patients with type 2 diabetes. Horm Metab Res 35(3):189–196CrossRefPubMedGoogle Scholar
  15. 15.
    Fritsche A, Schweitzer MA, Haring HU (2003) Glimepiride combined with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. A randomized, controlled trial. Ann Intern Med 138(12):952–959CrossRefPubMedGoogle Scholar
  16. 16.
    Lee P et al (2012) Comparison of safety and efficacy of insulin glargine and neutral protamine hagedorn insulin in older adults with type 2 diabetes mellitus: results from a pooled analysis. J Am Geriatr Soc 60(1):51–59CrossRefPubMedGoogle Scholar
  17. 17.
    Riddle MC, Rosenstock J, Gerich J (2003) The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 26(11):3080–3086CrossRefPubMedGoogle Scholar
  18. 18.
    Yki-Jarvinen H et al (2006) Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study. Diabetologia 49(3):442–451CrossRefPubMedGoogle Scholar
  19. 19.
    Eliaschewitz FG et al (2006) Therapy in type 2 diabetes: insulin glargine vs. NPH insulin both in combination with glimepiride. Arch Med Res 37(4):495–501CrossRefPubMedGoogle Scholar
  20. 20.
    Lepore M et al (2000) Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes 49(12):2142–2148CrossRefPubMedGoogle Scholar
  21. 21.
    Heinemann L et al (2000) Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo. Diabetes Care 23(5):644–649CrossRefPubMedGoogle Scholar
  22. 22.
    Linn T et al (2008) Nocturnal glucose metabolism after bedtime injection of insulin glargine or neutral protamine hagedorn insulin in patients with type 2 diabetes. J Clin Endocrinol Metab 93(10):3839–3846CrossRefPubMedGoogle Scholar
  23. 23.
    Currie CJ, Johnson JA (2012) The safety profile of exogenous insulin in people with type 2 diabetes: justification for concern. Diabetes Obes Metab 14(1):1–4CrossRefPubMedGoogle Scholar
  24. 24.
    Giugliano D et al (2011) Efficacy of insulin analogs in achieving the hemoglobin A1c target of <7 % in type 2 diabetes: meta-analysis of randomized controlled trials. Diabetes Care 34(2):510–517CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Hermansen K et al (2006) 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 29(6):1269–1274CrossRefPubMedGoogle Scholar
  26. 26.
    Investigators OT et al (2012) Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 367(4):319–328CrossRefGoogle Scholar
  27. 27.
    Pontiroli AE, Miele L, Morabito A (2011) Increase of body weight during the first year of intensive insulin treatment in type 2 diabetes: systematic review and meta-analysis. Diabetes Obes Metab 13(11):1008–1019CrossRefPubMedGoogle Scholar
  28. 28.
    Igel LI et al (2016) Metformin: an old therapy that deserves a new indication for the treatment of obesity. Curr Atheroscler Rep 18(4):16CrossRefPubMedGoogle Scholar
  29. 29.
    Polonsky W et al (2014) More satisfied, but why? A pooled patient-level analysis of treatment satisfaction following the initiation of insulin glargine vs. comparators in insulin-naive patients with type 2 diabetes mellitus. Diabetes Obes Metab 16(3):255–261CrossRefPubMedGoogle Scholar
  30. 30.
    Petrovski G et al (2014) Successful desensitization in patient with type 2 diabetes with an insulin allergy using insulin pump and glargine. Acta Diabetol 51(6):1073–1075CrossRefPubMedGoogle Scholar
  31. 31.
    Succurro E et al (2015) Bilateral lower limbs edema with “wooden” character induced by insulin glargine treatment. Acta Diabetol 52(4):809–811CrossRefPubMedGoogle Scholar
  32. 32.
    Iafusco D et al (2015) Lower limbs edema by insulin glargine treatment: two other cases in pediatrics. Acta Diabetol. doi: 10.1007/s00592-015-0797-x Google Scholar
  33. 33.
    Selam JL (2010) Evolution of diabetes insulin delivery devices. J Diabetes Sci Technol 4(3):505–513CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Asamoah E (2008) Insulin pen-the “iPod” for insulin delivery (why pen wins over syringe). J Diabetes Sci Technol 2(2):292–296CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Korytkowski M et al (2003) A multicenter, randomized, open-label, comparative, two-period crossover trial of preference, efficacy, and safety profiles of a prefilled, disposable pen and conventional vial/syringe for insulin injection in patients with type 1 or 2 diabetes mellitus. Clin Ther 25(11):2836–2848CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2016

Authors and Affiliations

  • Albrecht Fiesselmann
    • 1
  • Tobias Wiesner
    • 2
  • Holger Fleischmann
    • 3
  • Peter Bramlage
    • 4
    Email author
  1. 1.Diabetologische SchwerpunktpraxisBerlinGermany
  2. 2.MVZ Stoffwechselmedizin LeipzigLeipzigGermany
  3. 3.Sanofi Aventis Deutschland GmbHBerlinGermany
  4. 4.Institut für Pharmakologie und Präventive MedizinMahlowGermany

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