With Equal Training, Insulin Pumps No Better Than Injections

Miriam E Tucker

December 07, 2015

VANCOUVER, British Columbia — Use of insulin pumps among adults with type 1 diabetes did not lead to better glycemic control when compared with similarly trained users of multiple daily insulin injections, a new randomized controlled trial from the United Kingdom finds.

The findings were presented December 3, 2015 here at the World Diabetes Congress 2015 by Dr Simon Heller, professor of clinical diabetes, University of Sheffield, United Kingdom.

In general, people who initiate insulin pump therapy typically receive more training and education about insulin adjustments than do those who use multiple daily injections, and few previous studies comparing insulin pump with injection use have controlled for the amount of training and education received by the respective patient groups, Dr. Heller explained.

In the United Kingdom, only about 6% of adults with type 1 diabetes use insulin pumps, compared with about 40% in the United States, Dr Heller noted. (In children, those figures are 14% vs 47%, according to a recent study reported by Medscape Medical News.)

REPOSE Trial Didn't Collect Blood Glucose Data

To address whether there were differences between these groups if education was equivalent , the 2-year eight-center Relative Effectiveness of Pumps Over Structured Education (REPOSE) trial featured a skills-based structured training program developed in Germany called Dose Adjustment for Normal Eating (DAFNE), which focuses on flexible insulin therapy and self-management, teaching patients to match insulin dose to chosen food on a meal-by-meal basis.

A total 267 adults with type 1 diabetes all underwent DAFNE training and were randomized to use either a Medtronic insulin pump or multiple daily injections using twice-daily insulin detemir (Levemir, Novo Nordisk) plus insulin aspart (Novolog, Novo Nordisk).before meals or otherwise as needed.

Although some quality-of-life measures were significantly improved with pump use, the primary outcome — HbA1c values at 24 months — did not differ. In both groups, HbA1c values dropped about a half a percent point from a baseline mean of around 9%, with no significant differences between pump and multiple daily injections seen at 24 months.

"We believe these results support a care pathway for adults with type 1 diabetes that starts with initial structured training using multiple daily injections, with pumps offered later to those in whom the limitations of [multiple daily injections] interfere with effective self-management," Dr Heller said.

He added, "Structured training reduces the risk of severe hypoglycemia and leads to modest but long-lasting benefits in HbA1c and should be delivered much more widely. Even in the UK, only 10% of adults have had the opportunity to receive this training. That is far too low."

Asked to comment, Irl B Hirsch, MD, professor of medicine and chair of diabetes treatment and teaching at the University of Washington School of Medicine, Seattle, faulted the study for not emphasizing blood glucose testing. Indeed, Dr Heller explained in response to Dr Hirsch's question from the audience, the patients were advised to test five or more times a day but those data weren't collected as part of the study.

"We do things differently in the US. We download the pump, we download the meter, we look at the frequency of testing, and make adjustments based on the patterns we see," Dr Hirsch told Medscape Medical News, adding, "The disappointing thing is that they didn't collect those data. How can you do a study in type 1 diabetes and not collect glucose-monitoring data?"

Dr Hirsch noted that data his group analyzed from the United States–based T1D Exchange with patients using both finger-stick testing and continuous blood glucose monitoring (CGM) show that there is a strong relationship between access to blood glucose data and HbA1c, regardless of whether a patient uses a pump or injections.

CGM wasn't part of REPOSE. While the study protocol didn't forbid it, few patients were using it, Dr Heller said in response to another audience question.

Dr Hirsch said, "The mode of insulin delivery is becoming less important than the data. The data have always been important, but now that we have CGM, people do exquisitely well with [multiple daily injections] if they have access to CGM."

He also pointed out, "This was a very poorly controlled group of patients. We just don't see HbA1cs of 9 anymore.…At least in our clinic, this is not who comes to see us."

Dr Heller agreed that even with the DAFNE training, the level of glycemic control in REPOSE was not optimal in either insulin-delivery group. "I think DAFNE improves control. What it doesn't do is improve it sufficiently," he told Medscape Medical News, noting that the project has recently been funded to make revisions.

Glycemic Control Not Different at 2 Years

The 267 REPOSE study subjects had a mean age of 41 years, were about 60% male and mostly white, and had a type 1 diabetes duration of 15 to 16 years. Twelve percent of the pump group and 11% of the injection patients had experienced at least one severe hypoglycemic episode in the prior year, and about half of each group had at least one microvascular complication.

To be recruited, patients could not have a clinical indication for pump use (eg, hypoglycemic unawareness) and had to express no particular preference for either the pump or injections.

With DAFNE, participants received 38 hours of teaching by trained diabetes specialist nurses and dieticians, delivered to groups of six to eight patients each over 5 consecutive days. In the pump group, the original DAFNE program included modifications tailored to pump use.

After an initial 6-week visit, patients were seen at 6-month intervals throughout the rest of the study (in contrast to the 3-month intervals between visits that are recommended in the United States). Follow-up data at 24 months were available for 128 pump and 120 injection patients.

The mean HbA1c, which at baseline was 9.3% for the pump group and 9.0% for the injection patients, dropped overall by a significant 0.54 percentage points at 24 months. For the 224 patients with baseline HbA1c values of 7.5% or greater, the overall drop was 0.64 percentage points, also significant.

The mean percentage point drops were 0.84 for the pump group and 0.42 with the injections. After adjustment for center, DAFNE course, and baseline HbA1c, the mean difference in HbA1c between the pump and injection groups was a nonsignificant reduction of 0.23 percentage points (P = .121).

The proportions of patients achieving an HbA1c less than 7.5% at 24 months were 22.7% with the pump and 20.8% with injections, also not significantly different (P = .523).

There were 11 patients who switched from pumps to injections, resulting in a change in HbA1c from 10.4% to 9.7% at 24 months. Another seven switched from injections to pumps, dropping from 10.3% to 8.3%.

With those 18 protocol violators excluded, the mean difference between the two groups among the remaining subjects was 0.34 percentage points, a statistically significant difference in favor of pumps (P = .018), Dr Heller noted.

Hypoglycemia Halved With Training

In the overall group of 267 patients, the average number of severe hypoglycemic episodes per patient per year was reduced from 0.17 to 0.10 during follow-up in REPOSE.

The incidence rate ratio for the number of severe hypoglycemic episodes over 24 months, compared with the year before baseline, was 0.46 (P = .021).

"Halving the risk of severe hypoglycemia.…This kind of training has shown that consistently in the UK and Germany," Dr Heller noted.

The drop in severe hypoglycemia was similar in the pump and injection groups (P = .766).

Overall, there were improvements in measures of quality of life, fear of hypoglycemia, anxiety and depression, and treatment satisfaction, with no differences between the groups on several of the scores.

However, on scores of diet restrictions, there was more improvement in the pump arm at 24 months (P = .04). The pump group also scored better on measures of daily hassle (P = .006) and treatment satisfaction (P = .067 at 6 months and P < .001 for both 12 and 24 months).

Serious adverse events were mostly comparable, but there were more DKA episodes in the pump group, 17 (12.9%) vs five (3.7%) in the injection arm.

However, Dr Heller pointed out that most of these occurred in the first year and included three of the patients who switched from injections to the pump. Most of the DKA episodes were due to infections, with a smaller number attributed to set failures.

Dr Hirsch commented, "I would expect to see more DKA in a pump patient if they're not doing much testing."

Findings Will Extend Pump Use in United Kingdom

Dr Heller told Medscape Medical News that he expects these findings to extend pump use in the United Kingdom to more patients who demonstrate that they are willing to actively manage their diabetes.

"I think you should do skills training first.…I think this gives us an opportunity in a very robust way to put people through training, which I think in the United States doesn't happen sufficiently for people on multiple daily injections."

Dr Hirsch added, "I congratulate [Heller] for doing such a large head-on-head study. But I think the standard of care is different in the UK than the US….I'm glad he did it, but we can't apply it here in the US."

Indeed, Dr Heller concluded from the podium, "Further work is needed in the UK to develop effective approaches to support people in achieving tighter glucose targets while we wait for the artificial pancreas to become generally available."

In 2015-2016, the DAFNE industry sponsors are Eli Lilly and Abbott Diabetes Care. Dr Heller has done advisory work for Novo Nordisk, Eli Lilly, and Sanofi and given talks for all three companies. He has also received consulting fees or honoraria from Takeda, MSD, AstraZeneca, Johnson & Johnson, and Boehringer Ingelheim. Medtronic supplied the pumps for the trial but had no influence over study design, analysis of the results, or the presentation or upcoming paper. Dr Hirsch has done research with Novo Nordisk and consulted for Abbott, BD, and Roche. He has no relationships with insulin-pump companies.

World Diabetes Congress 2015; Vancouver, British Columbia. Abstract 319 , presented December 3, 2015.

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