Are Newer Diabetes Drugs Improving Glycemic Control?

Miriam E Tucker

October 10, 2016

Neither glycemic control nor severe hypoglycemia rates improved between 2006 and 2013 among US adults with type 2 diabetes, despite a dramatic shift to the use of newer glucose-lowering drugs during that time period, new research shows.

The findings, from an analysis of claims data from 1.66 million privately insured and Medicare Advantage patients, were published online September 22 in Diabetes Care by endocrinologist Kasia J Lipska, MD, of Yale University, New Haven, Connecticut, and colleagues.

"We have a great number of medications to lower glucose levels in people with type 2 diabetes. Our findings suggest that we adopted them in our clinical practice as they became available on the market. However, we did not find population-level improvements in glycemic control or rate of severe hypoglycemia. These results were somewhat disappointing, since the newer agents cost much more and don't typically cause hypoglycemia," Dr Lipska told Medscape Medical News.

However, she says that the results should not discourage prescribing of newer medications, especially given the recent results from the cardiovascular end-point trials EMPA-REG, LEADER, and SUSTAIN-6 suggesting cardiovascular benefit that may be independent of glucose-lowering.

"We need more outcomes studies, including for the available older and cheaper agents, so we can understand their impact beyond just glycemic control," she stressed.

Asked to comment, Michael A Bush, MD, an endocrinologist with the University of California, Los Angeles Geffen School of Medicine and coauthor of the American Association of Clinical Endocrinologists' type 2 diabetes management algorithm, points out that the period studied reflects the time when the dipeptidyl peptidase-4 (DPP-4) inhibitors were just becoming widely adopted as alternatives to the thiazolidinediones following the reported concerns about the latter's cardiovascular safety, but the data include very little use of glucagonlike peptide 1 (GLP-1) receptor agonists and no sodium glucose cotransporter-2 (SGLT2) inhibitors, which came along later and are now increasingly used.

"It's always interesting to see the trends in pharma utilization in this country.…This paper represents 2006 to 2013. An endocrinologist would view 'new medications' for diabetes as GLP-1 agonists and SGLT2 inhibitors," Dr Bush told Medscape Medical News.

"I'd be very interested to see, after SGLT2 inhibitors are more solidly utilized in the diabetes world — and I think they will be — how that influences drug utilization over the next 10 years and what kind of data will come out in terms of both A1c attainment and hypoglycemia risk," he added.

Dramatic Shift in Drug Utilization

For the research, Dr Lipska and colleagues conducted a retrospective analysis of medical and pharmacy claims from a large database (OptumLabs Data Warehouse) that includes more than 100 million enrollees in both private insurance and Medicare Advantage plans throughout the United States. Study subjects were 1,657,610 adults with type 2 diabetes enrolled for at least 1 year during 2006–2013.

From 2006 to 2013, there were increases in the use of metformin (from 47.6% to 53.5%), DPP-4 inhibitors (0.5% to 14.9%), GLP-1 agonists (3.3% to 5.0%), and insulin (17.1% to 23.0%). Over the same time period, declines were seen in the use of sulfonylureas (38.8% to 30.8%) and thiazolidinediones (28.5% to 5.6%). All changes were significant (P < .001).

The increased insulin use was driven primarily by uptake of insulin analogs, with increases in basal analogs from 10.9% to 19.3% and rapid-acting analogs from 6.7% to 11.6% (both P < .001).

Worsening of Glycemic Control Seen; Hypoglycemia Rates Unchanged

Laboratory testing for HbA1c was available for 26% of the total sample.

From 2006 to 2013, the proportion of patients with HbA1c levels of 9% or greater rose from 9.9% to 12.2%, and the proportion of those with HbA1c levels 8% to 9% increased from 9.9% to 10.6% (P for trend < .001).

At the same time, the proportion with HbA1c 7% to 8% didn't change significantly (23.8 to 23.0%, P = .31), while those achieving HbA 1c less than 7% declined from 56.4% in 2006 to 54.2% in 2013 (P < .001).

Poor glycemic control (HbA1c > 9%) was most common among the youngest patients but increased slightly over time across all age groups.

The finding of worsening glycemic control may have to do with the 2008 publication of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial data, which raised concerns about a possible adverse cardiovascular mortality risk from intensive glycemic control, Dr Lipska and colleagues postulate.

Meanwhile, age- and sex-standardized rates of severe hypoglycemia requiring a hospital visit (emergency, admission, or observation) among people using diabetes medications were 1.3 events per 100 person-years in both years, 2006 and 2013 (P for trend over time 0.72).

Severe hypoglycemia was more common among the oldest patients and those with multiple comorbidities compared with younger, healthier adults.

Cost vs Benefit

Dr Bush points out that in addition to the need for more recent glycemic data for patients using GLP-1 agonists and SGLT2 inhibitors, an examination of the costs vs benefits also needs to include the recent clinical trial findings of cardiovascular benefit with some of these newer agents.

"If you now look at that in the context of the new data on CV protection — which obviously needs to be confirmed by other studies and in other medications — you need a broader sense of what is cost-effective, because effectiveness in diabetes means not just blood glucose control but prevention of serious complications."

In their paper, Dr Lipska and colleagues put it this way: "Although the use of newer and more expensive agents may have other important benefits, further studies are needed to define the value and cost-effectiveness of current treatment options."

This study was funded in part by the National Center for Advancing Translational Sciences, a component of the National Institutes of Health. Dr Lipska receives support from the National Institute on Aging and the American Federation of Aging Research through the Paul Beeson Career Development Award and the Yale Claude D Pepper Older Americans Independence Center. Disclosures for the coauthors are listed in the article. Dr Bush is on the speaker's bureau for Lilly, Novo Nordisk, AstraZeneca, Boehringer Ingelheim, and Janssen and is a consultant for Janssen and Lilly.

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Diabetes Care. Published online September 22, 2016. Abstract

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