Super-Fast Novolog performs better in Type 1 Diabetes

Faster-acting novolog lowers A1c, 1 hour and 2 hours postprandial glucose more than conventional novolog. About 1,000 type 1 diabetes participants were followed for 26 weeks. Adverse events were overall similar between the two insulins.

Faster-acting novolog would provide more flexibility and glycemic control to a patient who injects insulin immediately after meals.

Based on these data I would anticipate FDA-approval of the super-fast novolog.

GT

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Diabetes Care

Phase 3 Trial

July 2017

Objective: This multicenter, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulin aspart (FASTER aspart/novolog) versus conventional insulin aspart/novolog in adults with type 1 diabetes.

Research Design and Methods: The primary end point was HbA1c change from baseline after 26 weeks. After an 8-week run-in, subjects were randomized (1:1:1) to double-blind mealtime faster novolog (n = 381), conventional novolog (n = 380), or open-label postmeal faster novolog (n = 382) โ€” each with insulin detemir/levemir.

Results:

HbA1c was reduced in both treatment groups, and noninferiority was confirmed for both mealtime and postmeal faster novolog to conventional novolog.

Mealtime faster novolog statistically significantly reduced HbA1c versus conventional novolog (P = 0.0003). Postprandial plasma glucose (PPG) increments were statistically significantly lower with mealtime faster novolog at 1 and 2 hour after the meal test; superiority to conventional novolog for the 2-h PPG increment was confirmed.

The overall rate of confirmed hypoglycemic episodes (<56 mg/dL) and safety profiles were similar between treatments.

Conclusions:

Faster novolog effectively improved HbA1c, and noninferiority to conventional novolog was confirmed, with superior PPG (postprandial plasma glucose) control for mealtime faster novolog vs. conventional novolog.

Subjects randomized to postmeal faster novolog for all meals maintained HbA1c noninferior to that obtained with mealtime conventional novolog.


More from the publication:

Postprandial glycemic control is an essential component for meeting HbA1c target levels of 6.5โ€“7%. Such targets are recommended by several guidelines to reduce the incidence and slow the progression of diabetes-related complications. Yet, limiting postprandial plasma glucose (PPG) excursions is one of the most challenging aspects in achieving adequate glycemic control.

Basal-bolus insulin therapy in type 1 diabetes aims to replace physiologic insulin secretion. Rapid-acting insulin analogs, insulins novolog, glulisine, and lispro, were developed to control PPG excursions more effectively than regular human insulin (RHI), primarily by offering a faster onset and shorter duration of action.

Innovative modifications of insulin formulations and delivery methods that offer ultrafast insulin time-action profiles aim to further improve PPG control by accelerating insulin absorption and appearance in the bloodstream. Fast-acting insulin novolog (faster novolog; an ultrafast mealtime insulin) is conventional insulin novolog (conventional novolog; NovoRapid/NovoLog) in a new formulation; nonclinical data demonstrate that addition of niacinamide promotes the formation of insulin novolog monomers after subcutaneous injection, facilitating a more rapid rate of insulin novolog absorption across the endothelium into the blood.

  • In adults with type 1 diabetes, subcutaneous injection of faster novolog was associated with twice-as-fast onset of appearance in the bloodstream (4 vs. 9 min).
  • Twofold higher insulin concentration.
  • And 74% greater insulin action in the first 30 min compared with conventional novolog.
  • Furthermore, in the recently completed phase 3 clinical trials, faster novolog improved 1-h PPG control vs. conventional novolog when administered as part of a basal-bolus regimen.
  • And demonstrated superior glycemic control vs. basal-only therapy in subjects with type 2 diabetes.

A large proportion (81.4%) of people with diabetes would like their insulin regimen to fit with their daily life changes, and the option to take their insulin dose after a meal when necessary may address this need.

The objective of this double-blind trial was to confirm the efficacy of faster novolog in terms of glycemic control compared with mealtime conventional novolog after 26 weeks of randomized treatment. The current trial confirmed that, in subjects with type 1 diabetes on a basal-bolus regimen, both mealtime and postmeal faster novolog are noninferior to mealtime conventional novolog regarding HbA1cchange from baseline. Switching to mealtime or postmeal faster novolog was effective in improving glycemic control: the reduction in HbA1c with mealtime faster novolog was moderately, yet statistically significantly, greater than with conventional novolog. After 26 weeks of treatment, subjects receiving mealtime faster novolog were almost 1.5 times as likely to achieve the HbA1ctarget of <7.0% than those receiving conventional novolog.

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In certain situations, postmeal dosing of insulin may offer increased flexibility compared with mealtime dosingโ€”for instance, when an individual is unable to predict the exact timing or carbohydrate content of a meal in advance (e.g., on social occasions), when experiencing lack of appetite or nausea (e.g., the very elderly or frail), when appetite is unpredictable (e.g., children), if an injection is forgotten, or if an individual is anxious about severe hypoglycemia. Subjects randomized to dosing faster novolog postmeal for all meals maintained overall glycemic control noninferior to that obtained with mealtime conventional novolog, indicating that flexibility in timing of dose with faster novolog does not lead to worsening of glycemic control.

Treatment with faster novolog was well tolerated by the subjects in this trial, and no safety concerns were raised. Overall, there were no clinically relevant differences in the TEAE profiles across all three treatment groups. No statistically significant difference was seen in overall rate of severe or BG-confirmed hypoglycemic episodes between faster novolog (mealtime or postmeal) and conventional novolog. The timing of hypoglycemia in relation to a meal usually reflects the time-action profile of the administered insulin formulation. Thus, as expected, there was a higher rate of hypoglycemia in the first hour after a meal in the mealtime faster novolog arm than in the conventional novolog arm. This observation is consistent with the differing clinical pharmacology profiles of faster novolog and conventional novolog.

Together with the results of previous studies, this trial has demonstrated that faster novolog given at mealtimes is noninferior to conventional novolog in terms of HbA1c reduction while offering superior control of PPG excursions, without increased risk of overall hypoglycemia. Additionally, faster novolog offers the option of dosing up to 20 min postmeal while retaining overall glycemic control and without increased rates of overall hypoglycemia. This is an incremental step in more closely replicating the physiologic response of endogenous insulin release after a meal.