Clinical Briefs

By Louis Kuritzky, MD

Insulin Pump Outperforms Multiple Injections in Type 2 Diabetes

Source:Reznik Y, et al. Lancet 2014;384:1265-1272.

Sometimes despite best efforts on the part of the clinician and the type 2 diabetes patient, A1c goals are not met. Although in some circumstances the underlying limitation to goal attainment is readily discernible (hypoglycemic episodes, non-compliance, medication misadministration, excessive weight gain, other adverse effects), it is not always so clear.

The combination of bolus insulin with basal insulin is designed to mimic endogenous insulin production in healthy individuals. Numerous titration schedules for both components have proven effective in clinical trials. Nonetheless, there remains a population for whom basal-bolus insulin is not sufficiently effective. Might the insulin pump provide better control in such patients?

Reznik et al performed an open-label trial comparing insulin pump treatment vs optimized basal-bolus dosing (n = 331) among patients who had previously not been able to attain A1c goals using multiple daily doses of insulin. The mean baseline A1c at enrollment was 9.0%. At 6 months, the insulin pump treatment group enjoyed a substantially greater A1c reduction than the optimized basal-bolus dosing group (1.0% vs 0.4%).

It would be easy to walk away from this study with the simplistic conclusion "the pump is just better," but that conclusion may be premature. First, recall that the group enrolled in the trial had already demonstrated that they were not highly effective in utilization of multiple daily insulin doses (baseline A1c 9.0% despite utilization of basal-bolus insulin), so we should not be surprised that the treatment methodology that didn’t work before didn’t work again! Second, despite the insulin pump, the mean A1c reduction at the end of the 6-month trial was still insufficient to bring most patients to A1c goal (mean A1c in the pump group = 7.9%). Finally, insulin pump treatment is considerably more expensive than multiple injections.

When Basal Insulin Plus Metformin Is Not Enough

Source: Diamant M, et al. Diabetes Care 2014; 37:2763-2773.

When lifestyle intervention is insufficient to attain control, pharmacologic treatment of type 2 diabetes is generally initiated with metformin, unless contraindications exist or GI intolerance occurs. Second-step pharmacotherapy choices are diverse, but use of basal insulin is a common next step. If glycemic goals are not attained with the metformin/basal insulin combination, what next?

Since postprandial glucose excursions are typically the main component of excess glucose load once metformin and basal insulin have been optimized, a logical next step has been to incorporate mealtime (bolus) rapid-acting insulin analogues. Unfortunately, despite the success that may be attained with this methodology, weight gain from the additional insulin is not uncommon, and the incidence of hypoglycemic episodes typically increases.

GLP1 agonists can also have particular efficacy for postprandial glucose excursions. This head-to-head trial compared outcomes of adding bolus insulin vs exenatide for patients who had not attained A1c goals (mean baseline A1c = 8.3%) on metformin plus basal insulin. Patients (n = 627) were treated for 30 weeks.

At the conclusion of the trial, A1c reductions were essentially equivalent for GLP1 agonist or bolus insulin as add-on to metformin/basal insulin (1.1% decrease in A1c for either add-on). As would be anticipated, weight decreased with exenatide and increased with bolus insulin.

Patients not at goal with the combination of metformin plus basal insulin may achieve similar levels of control by adding either a GLP1 agonist or bolus insulin, albeit with significant weight change differences.

COPD Patients on Triple Therapy: The Safety of Inhaled Steroid Discontinuation

Source:Magnussen H, et al. N Engl J Med 2014; 371:1285-1294.

Bronchodilators (long-acting beta agonists and anticholinergics) form foundation therapy for chronic obstructive pulmonary disease (COPD), and have been found not only to provide symptomatic relief, but also reduce the frequency of acute exacerbations. When COPD becomes severe, and especially in patients with frequent exacerbations, it is appropriate to also include inhaled corticosteroids. Often, COPD patients are treated with triple therapy: a long-acting beta agonist (LABA), long-acting anticholinergic agent (LACA), and inhaled corticosteroid (ICS). Once stable, however, some have questioned whether continuation of the ICS exerts meaningful benefit.

To address this issue, Magnussen et al performed a double-blind trial among severe COPD patients (n = 2485). Patients on triple therapy (LABA + LACA + ICS) were randomized to either continue on that regimen or receive LABA + LACA + placebo ICS. The primary outcome of the study was time to first moderate or severe COPD exacerbation.

ICS withdrawal did not lead to any significant change in time to COPD exacerbation, dyspnea, or other measures of health status at 1 year. These data would suggest that consideration of ICS discontinuation in patients on triple therapy may generally be accomplished without worsening likelihood of exacerbations.