Diabetes, osteoporosis, and low testosterone considered

An upcoming talk at Internal Medicine Meeting 2017 seeks to help internists understand common endocrine conditions that have seen advances in therapies or care.

General internists may find that a few key issues make up their endocrinology caseloads, so an update in that field will focus on the three topics that are most likely to come along: diabetes, osteoporosis, and male hypogonadism.

Jane E. Weinreb, MD, of UCLA and VA Greater Los Angeles Healthcare, specializes in endocrinology, diabetes, and metabolism. For her intended audience at the Update in Endocrinology at Internal Medicine Meeting 2017, Dr. Weinreb chose those three conditions, which were both prevalent and widely discussed in the literature in 2016.

“Those are the areas that general internists see the most of,” Dr. Weinreb said. “I also think that there are articles that have come out in the past year that are particularly pertinent to them.”

Diabetes. Because there is so much research and other progress being made in diabetes, Dr. Weinreb said she was challenged by narrowing down the material. In the end, she focused on two articles that can guide second-line therapy in patients with type 2 diabetes, one on liraglutide and one on empagliflozin.

The LEADER study and the EMPA-REG study resulted from an FDA mandate that every diabetes drug undergo large cardiovascular outcomes trials to demonstrate safety. Both these trials showed not only safety but cardiovascular risk reduction, Dr. Weinreb said.

“The goal is to show that it's no worse than other therapies, but these two studies show significant mortality benefits,” she said. “That's new in the diabetes arena.”

In the industry-funded LEADER study, published in the New England Journal of Medicine, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes was lower with liraglutide than with placebo. In the industry-funded EMPA-REG trial, which also was published in the New England Journal of Medicine, empagliflozin was similarly superior to placebo in improving reducing cardiovascular events, including mortality, in patients with type 2 diabetes and established cardiovascular disease.

“These drugs, in a matter of three to 3.8 years, showed mortality benefit,” Dr. Weinreb said. “Based upon how quickly this outcome was seen, those are off-target effects. We don't think those are glycemic effects.”

Also in diabetes, a new insulin pump that was approved in September 2016 uses a “smart algorithm” to learn an individual's insulin needs over the first 48 hours and then self-adjust the basal rate every five minutes.

“For a type 1 diabetic who has variations in basal insulin needs due to changes in sensitivity over the day, having a pump that is auto-adjusting the basal insulin supplied is really pretty aspirational, and that's a second step toward an artificial pancreas,” Dr. Weinreb said.

Osteoporosis. There is currently a crisis of undertreatment for osteoporosis, stemming at least in part from fears of adverse effects associated with bisphosphonates, Dr. Weinreb said.

She pointed out that a drop in bisphosphonate use seemed to coincide with FDA warnings about associated risk of osteonecrosis of the jaw, atrial fibrillation, and atypical femoral fractures. But these are all uncommon side effects, whereas fractures are common, especially in patients with a prior fracture.

“That we are not treating these patients is kind of a crime,” she said. “We need to put it in perspective for our patients and for ourselves.”

On the plus side, two new drugs that will be coming on the U.S. market actually build bone, according to Dr. Weinreb. Romosozumab, an anti-sclerostin antibody, enhances bone formation and turns off bone reabsorption. “It does exactly what you would want a new bone drug to do,” she said.

The FRAME study, published in the New England Journal of Medicine, concluded that in postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months, with lower risk of clinical fracture evident at one year.

The second drug, abaloparatide, a PTHrp analog, binds to the parathyroid hormone receptor as teriparatide, a recombinant form of parathyroid hormone, would. However, Dr. Weinreb said, “It signals in a slightly different way. We think it does a better job of enhancing bone formation without simultaneously stimulating bone reabsorption.”

The ACTIVE trial, published in JAMA, showed that use of subcutaneous abaloparatide was associated with reduced risk of new vertebral and nonvertebral fractures over 18 months compared with placebo.

“It would be really fabulous for the internal medicine docs to know that when someone has severe osteoporosis or recent fracture with severe osteoporosis, maybe there's something that we can do besides put them on a bisphosphonate,” she said. “These are two new anabolic therapies coming onto the market this year. And hopefully internists will consider them in high-risk patients because building bone in that first year will help prevent fractures.”

Male hypogonadism. Many older men have low testosterone levels, Dr. Weinreb said, but which patients to treat for this has never really been clear. The Testosterone Trials, a set of seven trials set up to look at older men with low testosterone and symptomatic hypogonadism, attempt to answer that question.

Three of these seven studies were incorporated into one paper that appeared in the New England Journal of Medicine. The first considered sexual function and desire, the second physical function, and the third vitality, or as Dr. Weinreb called it, “spunk.”

The study showed that raising testosterone concentrations for one year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance.

“I don't know if this is something that we wouldn't have expected, but now we have data that supports it. It's very clear that [testosterone] improves libido, energy, and even mood in men with symptomatic hypogonadism,” Dr. Weinreb said. “Those are the patients most appropriately treated with testosterone therapy.”

Dr. Weinreb's talk will be held today from 4:30 to 5:30 p.m. in Ballroom 20D.