An Evidence-Based Insulin Intensification Regimen
Abstract & Commentary
By Jeff Unger, MD, ABFP, FACE
Medical Director, Unger Primary Care Medicine Group,Rancho Cucamonga, CA
Dr. Unger has received research grants from Novo Nordisk and serves on the advisory board and speaker's bureau of Novo Nordisk.
Synopsis: This study provides clinicians with valuable guidance on a technique by which insulin therapy may be intitiated and intensified using a safe, timely, and rational therapeutic approach.
Source: Rodbard HW, et al. Treatment intensification with stepwise addition of prandial insulin aspart boluses compared with full basal-bolus therapy (FullSTEP Study): A randomised, treat-to-target clinical trial.Lancet Diabetes Endocrinol 2014;2:30-37.
This is a 32-week, randomized, open-label, two-arm, parallel group treat-to-target study comparing the effectiveness of a stepwise prandial insulin dosing approach vs a standard basal-bolus insulin regimen in 401 patients with type 1 diabetes. The mean baseline A1C in this cohort was 7.9% and the mean duration of diabetes was 12.6 years. Basal-bolus patients received insulin aspart prior to each meal. Patients in the stepwise group received one bolus dose at a single meal. After 11 and 22 weeks, additional meals were targeted if subject's A1Cs remained ≥ 7%. The primary endpoint was non-inferiority of stepwise mealtime dosing vs basal-bolus dosing as assessed by the A1C at 32 weeks. At study end, the A1C change from baseline was -0.98% (95% confidence interval [CI], -1.09 to -0.87) for the stepwise group and -1.12% (-1.23 to -1.00) for the basal-bolus group; mean treatment difference 0.14 (95% CI, -0.02 to 0.30), non-significant (P = 0.0876). Fewer hypoglycemic episodes occurred in the stepwise group than in the basal-bolus group.
Stepwise prandial insulin intensification provides glycemic control non-inferior to a full basal-bolus regimen after 32 weeks, with significantly lower hypoglycemia risk.
Although primary care physicians appear quite competent in initiating basal insulin, the timing and titration of prandial insulin is more challenging. The initiation of basal bolus insulin requires patients to develop immediate expertise at diabetes self-management skills. Blood glucose values must be checked prior to each meal and often 2 hours after eating to assess the efficacy of the prescribed prandial insulin dose. Variables such as timing of insulin boluses in relation to ambient blood glucose values, insulin correction calculations, fat content of meals, anticipated post meal activity levels, and fear of hypoglycemia can equate a prandial dose of insulin with the famous Disneyland ride, "Mr. Toad's Great Adventure!" Rodbard points out that initiating prandial insulin slowly and meticulously over several weeks will allow patients to develop expertise in self-monitoring, avoidance of hypoglycemia, and become more adherent to the treatment regimen.
Clinicians understand the importance of insulin intensification for poorly controlled patients with type 2 diabetes mellitus (T2DM). Unfortunately, adherence to intensive insulin regimens remains an elusive target, as 89% of T2DM patients do not inject outside of the home!1,2
During an 8-week run-in period, subjects were transferred from pre-existing therapies to insulin detemir at bedtime. Dose titration followed the protocol adapted from the TITRATE study (see Table).
|Insulin Detemir Titration Schedule Using a 70-90 mg/dL Fasting Glucose Target|
|Average fasting plasma glucose of 3 consecutive days (mg/dL)||Insulin detemir dose adjustment*|
|< 70||-3 units|
|> 90||+3 units|
|*Initial detemir dose was 0.1-0.2 U/kg or 10 U at dinner or bedtime3|
Patients in the basal-bolus cohort of the FullSTEP study were initiated on two units of aspart insulin prior to each meal. Individuals in the stepwise group injected 4 units of aspart prior to the meal with the highest carbohydrate content as assessed by each patient at baseline. All patients used a self-titration algorithm to achieve a plasma glucose target of 72-130 mg/dL prior to the subsequent premeal glucose measurement. Subjects were advised to self-adjust their insulin aspart doses daily on the basis of the previous day's blood glucose values.
This study provides clinicians with valuable guidance on a technique by which insulin therapy may be intitiated and intensified using a safe, timely, and rational therapeutic approach.
- Norton E. J Diabetes Sci Technol 2009;3:1521-1522.
- Roper Global Diabetes Program. 2006 U.S. Diabetes Patient Market Study, management summary report. 2007.
- Blonde L, et al. Diabetes Obes Metab 2009;11:623-631.