The Barmer study: impact of standardized warming of the injection site to enhance insulin absorption and reduce prandial insulin requirements and hypoglycemia in obese patients with diabetes mellitus

Abstract

Background:

The primary objective of this prospective controlled study was to investigate the impact of standardized injection-site warming on prandial rapid acting insulin dose and glycemic control when studied under real-world conditions.

Methods:

All 145 participating patients (51 female, 94 male, 13 type 1 and 132 type 2 patients, age: 61.6 ± 8.4 yrs, HbA1c: 7.19 ± 0.50%) were treated with intensive insulin glargine and short-acting insulin analog therapy. After a 4 week treatment optimization run-in period, patients were randomized to continue therapy for three months without (control) or with a local injection-site warming device (InsuPad). Observation parameters included HbA1c, insulin dose, frequency of hypoglycemia, body weight and adverse events.

Results:

HbA1c improved in both arms until study end (control group: 6.3 ± 0.5%; injection-site warming device: 6.3 ± 0.5%; both p < 0.001 vs. baseline). To achieve this good control, patients in the control group needed to increase the daily prandial insulin dose by 8.1% (from 66 ± 31 U to 71 ± 38 U, p < 0.05) with stable basal insulin requirements. Patients who used the injection-site warming device required less prandial insulin (70 ± 43 U to 55 ± 34 U; −19%, p < 0.001) and slightly more basal insulin (+3.9%). Total daily insulin dose increased in the control group (+3.7%) and decreased with warming device use (−8.6%, p < 0.001). The number of hypoglycemic events (<63 mg/dL) during the observation period was higher in the control group (6.2 ± 9.9/patient vs. injection-site warming device: 3.3 ± 4.8/patient, p < 0.05). Main study limitations can be seen in the open label design reliability of the collected dose information and the very obese patient cohort.

Conclusion:

When treating obese patients to target with insulin therapy, use of an injection-site warming device for 3 months resulted in a lower frequency of hypoglycemic events and a reduction in prandial insulin analog requirements. If these results are confirmed in other patient populations, an injection-site warming device may be useful in achieving treatment targets with a safer and more efficient basal bolus therapy in insulin-treated patients with type 1 and type 2 diabetes.

Keywords::

• Injection site warming device
• Insulin therapy
• Prandial insulin dose
• Rapid-acting insulin

Transparency

Declaration of funding

This study was funded by Insuline Medical, Petach Tikva, Israel.

Author contributions: A.P.: contributed to study design, researched data, analyzed data, contributed to discussion, wrote manuscript, reviewed/edited manuscript. N.H.: contributed to study design, researched data, contributed to discussion, reviewed/edited manuscript. K.F.: researched data, contributed to discussion, reviewed/edited manuscript. T.F.: researched data, contributed to discussion, reviewed/edited manuscript. T.B.: researched data, contributed to discussion, reviewed/edited manuscript. G.B.: contributed to study design and discussion, reviewed/edited manuscript. R.N.: contributed to study design and discussion, reviewed/edited manuscript. I.R.: contributed to study design and discussion, reviewed/edited manuscript. T.H.: contributed to study design, researched data, contributed to discussion, reviewed/edited manuscript.

Declaration of financial/other relationships

N.H., K.F., T.F., T.B., and T.H. have received research grants, speaker fees and travel support from Insuline Medical. A.P. and I.R. have received consultancy fees, research grants, speaker fees and travel support from Insuline Medical. G.B. and R.N. are employees and shareholders of Insulin Medical.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no other relevant financial relationships to disclose.

Acknowledgments

The authors thank all participating staff and patients from the following study centers: Behnke, Neuwied; Daikeler, Sinsheim, Forst, Mainz; Funke, Potsdam; Haak, Bad Mergentheim, Hanefeld, Dresden; Jakob Villingen-Schwenningen; Lorra, Bochum; Meyer, Essen; Segiet, Speyer.

Notes

*InsuPad is a registered trademark of Insuline Medical, Petach Tikva, Israel

†InsuPatch is a registered trademark of Insuline Medical, Petach Tikva, Israel

‡InsuPad is a registered trademark of Insuline Medical, Petach Tikva, Israel