Real-world evidence received lots of attention as drug makers looked to compare therapies within a class.
Clinical trial results shared the stage with real-world evidence at the 78th American Diabetes Association (ADA) Scientific Sessions, which took place June 22-26, 2018, in Orlando, Florida, as competition between drugs to treat diabetes brought out companies to comment on the findings.
From last week’s meeting are these 5 key takeaways:
1. A new study of canagliflozin finds no amputation risk.
OBSERVE-4D is a real-world study that evaluated claims data from 714,582 adults in the United States who took canagliflozin, other sodium glucose co-transporter-2 (SGLT2) inhibitors, and therapies other than SGLT2 inhibitors for type 2 diabetes (T2D). The study found no increased risk of below-the-knee amputations when comparing canagliflozin users to other SGLT2 inhibitor users or to those taking other medications for T2D.
Canagliflozin, sold as Invokana by Janssen, was found to have an increased risk of amputations in last year’s landmark CANVAS study, which showed a cardiovascular benefit. (FDA announced a boxed warning for the drug a few weeks before results were presented at last year’s ADA Scientific Sessions.) Physicians presenting information about CANVAS have said that because the study was a safety trial, the population was higher risk than the overall population that uses canagliflozin.
2. Sotagliflozin drives down A1C, weight in type 1 diabetes (T1D).
Positive results from the phase 3 inTandem1 study showed that at 52 weeks, patients with T1D had significantly lower glycated hemoglobin (A1C) after taking insulin alongside sotagliflozin, a dual inhibitor that targets both the SGLT2 and SGLT1 proteins responsible for glucose reabsorption. Results, which were published in Diabetes Care, also showed a lower incidence of severe hypoglycemia.
The study drug was tested at 2 doses: 200 mg and 400 mg. Those taking the 200 mg dose lowered A1C 0.25% more than placebo, and those taking the 400 mg dose lowered A1C 0.31% more after 52 weeks. Net clinical benefit—those who had A1C below 7% without hypoglycemia or diabetic ketoacidosis (DKA)—was also significantly higher than placebo at the 400 mg dose. However, treatment was linked to more cases of DKA.
3. CONFIRM shows insulin degludec improves A1C, reduces hypoglycemia more than insulin glargine U300.
In CONFIRM, a real-world evidence study of 4000 adults with type 2 diabetes starting basal insulin for the first time, patients taking insulin degludec, sold as Tresiba by Novo Nordisk, had significantly lower A1C after 6 months than those taking insulin glargine U300, sold as Toujeo by Sanofi. Drops in A1C were —1.5% for insulin degludec and –1.2% for insulin glargine U300. The study also showed that patients taking insulin degludec had a 30% lower rate of hypoglycemia, and that patients taking insulin glargine U300 had a 37% higher rate of discontinuing treatment. However, Sanofi released data from the BRIGHT study, which showed insulin glargine U300 was noninferior to insulin degludec.
4. Are cardiovascular outcomes trials worth the cost?
Ten years after the FDA began requiring drug manufacturers to study whether drugs for diabetes, obesity, and cardiovascular conditions are safe—meaning they don’t cause heart attacks—an ADA session examined whether these giant trials are worth the cost. Steven P. Marso, MD, medical director for cardiovascular services at HCA Midwest Health, said the studies are worthwhile—the unexpected discovery that empagliflozin was associated with fewer deaths, and the ability to differentiate between different drugs within a class added much to the field. But Darren K. McGuire, MD, MHSc, professor of the Department of Internal Medicine at the University of Texas Southwestern Medical Center, said it’s time to fine tune the trials to get more value from them. One evolution is that heart failure is becoming a primary endpoint. But McGuire would like to see the analyses tweaked to get new information about older therapies, like metformin.
5. Clinical inertia still keeps doctors from increasing therapy.
Researchers examining a large, national database found new results about an old problem: doctors often fail to increase therapy for patients with T2D, even when clinical indicators show they should. Data from 281,000 patients aged 18 to 75 were studied over more than 5 years, from January 2012 to June 2017. Six months after patients had an A1C ≥8%, 55% of the them showed no sign that medication had been prescribed or increased, or other action taken. A new diabetes prescription was seen in 35% of the patients (and 7.5% achieved an A1C < 8%), while 10% achieved glycemic control without a prescription. Reasons associated with clinical inertia—and no action—at both 6 months and 2 years included being African American, not having insurance, having a normal body mass index, and being on bolus insulin. Within 2 years, clinical inertia was reduced to 19%.