The University of Arizona (UA) Cancer Center has a new interim director, two hematologists have earned new positions at City of Hope, and an assistant professor has joined Fox Chase Cancer Center.

William Cance, MD, has been appointed interim director of the UA Cancer Center. In this role, he will oversee clinical operations and research at the center’s primary locations in Tucson and Phoenix. He will also lead the UA Cancer Center’s efforts to renew its 5-year Cancer Center Support Grant from the National Cancer Institute (NCI).

In addition to his new role, Dr. Cance is a professor at the UA Colleges of Medicine and Pharmacy in Phoenix. He is board certified in general surgery and specializes in thyroid cancer, parathyroid disease, sarcoma, and gastrointestinal cancer. Dr. Cance has received funding from NCI, has served on the NCI Board of Scientific Counselors, and is a member of NCI Subcommittee F.

In other news, Larry Kwak, MD, PhD, has been appointed the deputy director of the Hematologic Malignancies and Stem Cell Transplantation Institute at City of Hope in Duarte, Calif. Dr. Kwak will work with the director of the Institute, Stephen J. Forman, MD, to oversee recruitment, clinical and laboratory research, and faculty development.

Dr. Kwak is also director of the Toni Stephenson Lymphoma Center, vice president and deputy director of the comprehensive cancer center, and the Dr. Michael Friedman Professor in Translational Medicine. Dr. Kwak was named one of TIME magazine’s “100 Most Influential People,” received the Chang-Yul Oh Memorial Award from the Korean Medical Association, and won the Ho-Am Prize in Medicine.

Also at City of Hope, Tanya Siddiqi, MD, has been appointed director of the chronic lymphocytic leukemia (CLL) program within the Toni Stephenson Lymphoma Center of the Hematologic Malignancies and Stem Cell Transplantation Institute. In this role, Dr. Siddiqi will oversee research efforts related to CLL. This includes maintaining the CLL tissue bank she developed, conducting translational studies and clinical trials, and investigating novel therapies for CLL.

Dr. Siddiqi is also an associate clinical professor in the department of hematology & hematopoietic cell transplantation, is the supervising physician of City of Hope’s anticoagulation clinic, and works in the Gehr Family Center for Leukemia Research. Dr. Siddiqi is a member of the National Comprehensive Cancer Network panels for CLL/SLL/hairy cell leukemia and venous thromboembolism.

Lastly, James M. Martin, MD, has been appointed assistant professor in the hematology and bone marrow transplant program within the department of hematology/oncology at Fox Chase Cancer Center in Philadelphia.

Dr. Martin received a medical degree from Ohio State University, Columbus, and completed an internship and residency at Rhode Island Hospital/Brown University, in Providence. He joined Fox Chase Cancer Center/Temple University in 2016 for a 3-year fellowship.
 

Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.

[email protected]

The University of Arizona (UA) Cancer Center has a new interim director, two hematologists have earned new positions at City of Hope, and an assistant professor has joined Fox Chase Cancer Center.

William Cance, MD, has been appointed interim director of the UA Cancer Center. In this role, he will oversee clinical operations and research at the center’s primary locations in Tucson and Phoenix. He will also lead the UA Cancer Center’s efforts to renew its 5-year Cancer Center Support Grant from the National Cancer Institute (NCI).

In addition to his new role, Dr. Cance is a professor at the UA Colleges of Medicine and Pharmacy in Phoenix. He is board certified in general surgery and specializes in thyroid cancer, parathyroid disease, sarcoma, and gastrointestinal cancer. Dr. Cance has received funding from NCI, has served on the NCI Board of Scientific Counselors, and is a member of NCI Subcommittee F.

In other news, Larry Kwak, MD, PhD, has been appointed the deputy director of the Hematologic Malignancies and Stem Cell Transplantation Institute at City of Hope in Duarte, Calif. Dr. Kwak will work with the director of the Institute, Stephen J. Forman, MD, to oversee recruitment, clinical and laboratory research, and faculty development.

Dr. Kwak is also director of the Toni Stephenson Lymphoma Center, vice president and deputy director of the comprehensive cancer center, and the Dr. Michael Friedman Professor in Translational Medicine. Dr. Kwak was named one of TIME magazine’s “100 Most Influential People,” received the Chang-Yul Oh Memorial Award from the Korean Medical Association, and won the Ho-Am Prize in Medicine.

Also at City of Hope, Tanya Siddiqi, MD, has been appointed director of the chronic lymphocytic leukemia (CLL) program within the Toni Stephenson Lymphoma Center of the Hematologic Malignancies and Stem Cell Transplantation Institute. In this role, Dr. Siddiqi will oversee research efforts related to CLL. This includes maintaining the CLL tissue bank she developed, conducting translational studies and clinical trials, and investigating novel therapies for CLL.

Dr. Siddiqi is also an associate clinical professor in the department of hematology & hematopoietic cell transplantation, is the supervising physician of City of Hope’s anticoagulation clinic, and works in the Gehr Family Center for Leukemia Research. Dr. Siddiqi is a member of the National Comprehensive Cancer Network panels for CLL/SLL/hairy cell leukemia and venous thromboembolism.

Lastly, James M. Martin, MD, has been appointed assistant professor in the hematology and bone marrow transplant program within the department of hematology/oncology at Fox Chase Cancer Center in Philadelphia.

Dr. Martin received a medical degree from Ohio State University, Columbus, and completed an internship and residency at Rhode Island Hospital/Brown University, in Providence. He joined Fox Chase Cancer Center/Temple University in 2016 for a 3-year fellowship.
 

Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.

[email protected]

The University of Arizona (UA) Cancer Center has a new interim director, two hematologists have earned new positions at City of Hope, and an assistant professor has joined Fox Chase Cancer Center.

William Cance, MD, has been appointed interim director of the UA Cancer Center. In this role, he will oversee clinical operations and research at the center’s primary locations in Tucson and Phoenix. He will also lead the UA Cancer Center’s efforts to renew its 5-year Cancer Center Support Grant from the National Cancer Institute (NCI).

In addition to his new role, Dr. Cance is a professor at the UA Colleges of Medicine and Pharmacy in Phoenix. He is board certified in general surgery and specializes in thyroid cancer, parathyroid disease, sarcoma, and gastrointestinal cancer. Dr. Cance has received funding from NCI, has served on the NCI Board of Scientific Counselors, and is a member of NCI Subcommittee F.

In other news, Larry Kwak, MD, PhD, has been appointed the deputy director of the Hematologic Malignancies and Stem Cell Transplantation Institute at City of Hope in Duarte, Calif. Dr. Kwak will work with the director of the Institute, Stephen J. Forman, MD, to oversee recruitment, clinical and laboratory research, and faculty development.

Dr. Kwak is also director of the Toni Stephenson Lymphoma Center, vice president and deputy director of the comprehensive cancer center, and the Dr. Michael Friedman Professor in Translational Medicine. Dr. Kwak was named one of TIME magazine’s “100 Most Influential People,” received the Chang-Yul Oh Memorial Award from the Korean Medical Association, and won the Ho-Am Prize in Medicine.

Also at City of Hope, Tanya Siddiqi, MD, has been appointed director of the chronic lymphocytic leukemia (CLL) program within the Toni Stephenson Lymphoma Center of the Hematologic Malignancies and Stem Cell Transplantation Institute. In this role, Dr. Siddiqi will oversee research efforts related to CLL. This includes maintaining the CLL tissue bank she developed, conducting translational studies and clinical trials, and investigating novel therapies for CLL.

Dr. Siddiqi is also an associate clinical professor in the department of hematology & hematopoietic cell transplantation, is the supervising physician of City of Hope’s anticoagulation clinic, and works in the Gehr Family Center for Leukemia Research. Dr. Siddiqi is a member of the National Comprehensive Cancer Network panels for CLL/SLL/hairy cell leukemia and venous thromboembolism.

Lastly, James M. Martin, MD, has been appointed assistant professor in the hematology and bone marrow transplant program within the department of hematology/oncology at Fox Chase Cancer Center in Philadelphia.

Dr. Martin received a medical degree from Ohio State University, Columbus, and completed an internship and residency at Rhode Island Hospital/Brown University, in Providence. He joined Fox Chase Cancer Center/Temple University in 2016 for a 3-year fellowship.
 

Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.

[email protected]

The options for treating type 2 diabetes without insulin have grown beyond metformin to include a long list of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists that can be taken with or without metformin. These new drugs have cardiovascular and kidney benefits and help with weight loss, but they also carry risks and, according to some experts, their costs can be prohibitively expensive.
 

Given the medical community’s long-term experience with treating patients with metformin, and metformin’s lower cost, most of the physicians interviewed for this article advise using SGLT2 inhibitors and GLP-1 receptor agonists as second-line treatments. Others said that they would prefer to use the newer drugs as first-line therapies in select high-risk patients, but prior authorization hurdles created by insurance companies make that approach too burdensome.

“The economics of U.S. health care is stacked against many of our patients with diabetes in the current era,” Robert H. Hopkins Jr., MD, said in an interview.

Even when their insurance approves the drugs, patients still may not be able to afford the copay, explained Dr. Hopkins, professor of internal medicine and pediatrics and director of the division of general internal medicine at the University of Arkansas for Medical Sciences, Little Rock. “Sometimes patients can purchase drugs at a lower cost than the copay to purchase with the ‘drug coverage’ in their insurance plan – unfortunately, this is not the case with the newer diabetes medications we are discussing here.”

“SGLT2 inhibitors and GLP-1 agonists can cost several hundred dollars a month, and insurers often balk at paying for them. They’ll say, ‘Have you tried metformin?’ ” explained endocrinologist Victor Lawrence Roberts, MD, in a interview. “We have to work with insurance companies the best we can in a stepwise fashion.”

According to Dr. Roberts, 80% of his patients with diabetes struggle with the cost of medicine in general. “They’re either underinsured or not insured or their formulary is limited.

Douglas S. Paauw, MD, agreed in an interview that the newer drugs can be problematic on the insurance front.

“For some patients they aren’t affordable, especially for the uninsured if you can’t get them on an assistance program,” said Dr. Paauw, who is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the university.

Dr. Hopkins, who is on the Internal Medicine News board, noted that “unfortunately, the treatment of type 2 diabetes in patients who cannot achieve control with metformin, diet, weight control, and exercise is a story of the ‘haves’ and the ‘have nots.’ The ‘haves’ are those who have pharmacy benefits which make access to newer agents like SGLT2 inhibitors and GLP-1 agonists a possibility.”

“Most insurance companies are now covering select SGLT2 inhibitors and GLP-1 receptor agonists for appropriate patients and those companies that currently do not will soon have to,” said Dr. Skolnik, who is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

“The outcomes [associated with use of the new drugs] are robust, the benefits are large, and are well worth the cost,” he added.
 

The side effects

While others praised these drugs for their beneficial effects, they also noted that the side effects of these drugs are serious and must be discussed with patients.

GLP-1 receptor agonists are linked to gastrointestinal symptoms, especially nausea, while SGLT2 inhibitors have been linked to kidney failure, ketoacidosis, and more. The Food and Drug Administration warned in 2018 that the SGLT2 inhibitors can cause a rare serious infection known as Fournier’s gangrene – necrotizing fasciitis of the perineum.

“We have to tell our patients to let us know right away if they get pain or swelling in the genital area,” Dr. Paauw, who is on the Internal Medicine News board, noted. “The chance that an infection could explode quickly is higher in those who take these drugs.”

Amputation risks also are associated with taking the SGLT2 inhibitor canagliflozin (Invokana). The FDA requires the manufacturer of this drug to include a black-box warning about the risk of “lower-limb amputations, most frequently of the toe and midfoot,” but also the leg. In approval trials, the risk doubled versus placebo.

These amputation risks “put a damper on some of the enthusiasm on behalf of physicians and patients ... for taking this drug,” noted Dr. Roberts, who is a professor of internal medicine at the University of Central Florida, Orlando.

While a manufacturer-funded study released last year found no link to amputations, the results weren’t powerful enough to rule out a moderately increased risk.

“[If] you are at high risk for having an amputation, we really have to take this risk very seriously,” said John B. Buse, MD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill, in a presentation about the study at the 2018 annual scientific sessions of the American Diabetes Association.
 

The benefits

Despite these risks of adverse events, most interviewed agreed that the many benefits observed in those taking SGLT2 inhibitors or GLP-1 receptor agonists make them worth prescribing, at least to those who are able to afford them.

Both SGLT2 inhibitors and GLP-1 receptor agonists appear to have significant cardiovascular benefits. A 2019 meta-­analysis and systematic review found that both drugs reduced major adverse cardiac events by about 12% (Circulation. 2019 Apr 23;139[17]:2022-31).

“They don’t cause hypoglycemia, they lower blood pressure, they don’t cause weight gain, and they might promote weight loss,” noted Dr. Paauw.

SGLT2 inhibitors also have shown signs of kidney benefits. The CREDENCE trial linked canagliflozin to a lowering of kidney disorders versus placebo (N Engl J Med. 2019 Jun 13;380[24]:2295-306). “The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% confidence interval, 0.53-0.81; P less than .001), and the relative risk of end-stage kidney disease was lower by 32% (HR, 0.68; 95% CI, 0.54-0.86; P = .002),” the trial investigators wrote.

“They showed very nicely that the drug improved the kidney function of those patients and reduced the kidney deterioration,” said Yehuda Handelsman, MD, an endocrinologist in Tarzana, Calif., who chaired the 2011 and 2015 American Association of Clinical Endocrinologists’ Comprehensive Diabetes Guidelines. The study was especially impressive, he added, because it included patients with low kidney function.

SGLT2 inhibitors’ “diuretic mechanism explains why there is a substantial reduction in heart failure hospitalizations in patients who take these drugs,” said cardiologist Marc E. Goldschmidt, MD, director of the Heart Success Program at Atlantic Health System’s Morristown (N.J.) Medical Center, in an interview. “Both the EMPA-REG Outcome and the CREDENCE trials demonstrated substantial benefit of this class of medications by showing a lower risk of cardiovascular death as well as death from any cause and a lower risk of hospitalization for heart failure."

Overall, the SGLT2 trial data have been very consistent with a benefit for cardiovascular risk reduction, particularly in regard to heart failure hospitalizations and even in potentially preventing heart failure in diabetics,” he added.

Dr. Skolnik, a columnist for Family Practice News, cited SGLT2 inhibitors and GLP-1 receptor agonists’ ability to slow renal disease progression, promote weight loss, and prevent poor cardiac outcomes.“These drugs should be used, in addition to metformin, in all patients with diabetes and vascular disease. These proven outcomes are far better than we ever were able to achieve previously and the strength of the evidence at this point is very strong,” said Dr. Skolnik. “In addition to the benefits of decreasing the development of cardiovascular disease, serious heart failure, and slowing progression of renal disease, these two classes of medication have additional benefits. Both classes help patients lose weight, which is very different from what was found with either sulfonylureas or insulin, which cause patients to gain weight. Also both the SGLT2 inhibitors and the GLP-1 RAs [receptor agonists] have a low incidence of hypoglycemia. For all these reasons, these have become important medications for us to use in primary care.”

Other recent trials offer “very powerful data” about SGLT2 inhibitors, Dr. Roberts said. That’s good news, since “our approach needs to be toward cardiovascular protection and preservation as well as managing blood sugar.”An Israeli trial, whose results were released in May 2019 at the annual meeting of the American College of Cardiology, found that, compared with other glucose-lowering drugs, taking an SGLT2 inhibitor was associated with lower risks of heart failure hospitalization and all-cause mortality (HR, 0.54; 95% CI, 0.44-0.65; P less than .001). This trial also offered a new detail: The patients gained the benefit regardless of whether their baseline left ventricular ejection fraction was preserved or reduced (J Coll Cardiol. 2019 Mar;73[9]:suppl 1). The SGLT2 inhibitors used in this trial included dapagliflozin (Farxiga) and empagliflozin (Jardiance).

In another study released this year, a subanalysis of the DECLARE-TIMI 58 trial, researchers reported that the SGLT2 inhibitor dapagliflozin reduced risks of both major adverse cardiovascular events and heart failure hospitalization in the subset of patients with type 2 diabetes and prior myocardial infarction versus controls (Circulation. 2019 May 28;139[22]:2516-27). The absolute risk reduction for major adverse cardiovascular events was 1.9% (HR, 0.81; 95% CI, 0.65-1.00; P = .046), while it was 0.6% for heart failure hospitalization (HR, 0.85; 95% CI, 0.72-1.00; P = .055).

These and other studies “speak volumes about the efficacy of managing blood sugar and addressing our biggest nemesis, which is cardiovascular disease,” Dr. Roberts said. “It’s irrefutable. The data [are] very good.”

Dr. Paauw said an SGLT2 inhibitor or GLP-1 receptor agonist is best reserved for use in select patients with cardiovascular risks and type 2 diabetes that need management beyond metformin.

For example, they might fit a 70-year-old with persistent hypertension who’s already taking a couple of blood pressure medications. “If they have another cardiovascular risk factor, the cardiovascular protection piece will be a bigger deal,” he said. Also, “it will probably help lower their blood pressure so they can avoid taking another blood pressure medicine.”

Trials of both GLP-1 receptor agonists and SGLT2 inhibitors have shown benefits “in improving [major adverse cardiac events], with the SGLT2 class showing substantial benefit in improving both heart failure and renal outcomes as well,” noted Dr. Skolnik. “It is in this context that one must address the question of whether the price of the medications are worthwhile. With such substantial benefit, there is no question in my mind that – for patients who have underlying cardiovascular illness, which includes patients with existent coronary disease, history of stroke, transient ischemic attack, or peripheral vascular disease – it is far and away worth it to prescribe these classes of medications.”

Indeed, the American Diabetes Association and the European Association for the Study of Diabetes’ most recent guidelines now call for a GLP-1 receptor agonist – instead of insulin – to be the first injectable used to treat type 2 diabetes (Diabetes Care 2018 Dec; 41[12]:2669-701).

“For the relatively small number of my patients who have been able to access and use these medications for months or longer, more have tolerated the GLP-1 agonists than SGLT2 inhibitors primarily due to urinary issues,” noted Dr. Hopkins.

Dipeptidyl peptidase–4 inhibitors are another option in patients with type 2 diabetes, but research suggests they may not be a top option for patients with cardiovascular risk. A 2018 review noted that cardiovascular outcome trials for alogliptin (Nesina), saxagliptin (Onglyza), and sitagliptin (Januvia) showed noninferiority but failed to demonstrate any superiority, compared with placebo in patients with type 2 diabetes mellitus and high cardiovascular risk (Circ Res. 2018 May 11;122[10]:1439-59).
 

The combination therapies

Many of the newer drugs are available as combinations with other types of diabetes drugs. In some cases, physicians create their own form of combination therapy by separately prescribing two or more diabetes drugs. Earlier this year, a study suggested the benefits of this kind of add-on therapy: Diabetes outcomes improved in patients who took the GLP-1 receptor agonist semaglutide and an SGLT2 inhibitor (Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587[19]30066-X).

Dr. Roberts suggested caution, however, when prescribing combination therapies. “My recommendation is always to begin with the individual medications to see if the patient tolerates the drugs and then decide which component needs to be titrated. It’s hard to titrate a combination drug, and it doesn’t leave a lot of flexibility. You never know which drug is doing what.
 

Dr. Handelsman said some patients may need to take three medications such as metformin, an SGLT2 inhibitor, and a GLP-1 receptor agonist.

“I don’t recommend using the combinations if you’re not familiar with the drugs ... These are relatively new pharmaceuticals, and most of us are on a learning curve as to how they fit into the armamentarium. If a drug is tolerated with a good response, you can certainly consider going to the combination tablets,” he added.

There is at least one drug that combines these three classes: The newly FDA-approved Qternmet XR, which combines dapagliflozin (an SGLT2 inhibitor), saxagliptin (a GLP-1 receptor agonist), and metformin. As of mid-June 2019, it was not yet available in the United States. Its sister drug Qtern, which combines dapagliflozin and saxagliptin, costs more than $500 a month with a free coupon, according to goodrx.com. In contrast, metformin is extremely inexpensive, costing just a few dollars a month for a common starting dose.
 

What about adding insulin?

“Both [SGLT2 inhibitors and GLP-1 receptor agonists] work very well with insulin,” Dr. Handelsman said. “There is a nice additive effect on the reduction of [hemoglobin] A_1c. The only caution is that, although neither SGLT2 inhibitors nor GLP-1 receptor agonists cause hypoglycemia, in combination with insulin they do increase the risk of hypoglycemia. You may have to adjust the dose of insulin.”

Dr. Hopkins warned that cost becomes an even bigger issue when you add insulin into the mix.

“When insulin comes into the discussion, we are again stuck with astronomical costs which many struggle to afford,” he explained.

Indeed, the price tag on these drugs seems to be the biggest problem physicians have with them.

“The challenges in managing patients with diabetes aren’t the risks associated with the drugs. It’s dealing with their insurers,” noted Dr. Roberts.

Dr. Hopkins, Dr. Paauw, Dr. Roberts, and Dr. Syed reported no disclosures. Dr. Buse is an investigator for Johnson and Johnson. Dr. Goldschmidt is paid to speak by Novartis. Dr. Handelsman reported research grants, consulting work, and speaker honoraria from Amgen, Gilead, Lilly, Merck, Novo Nordisk, and others. Dr Skolnik reported nonfinancial support from AstraZeneca, Boehringer Ingelheim, Sanofi, and GlaxoSmithKline and personal fees from AstraZeneca, Boehringer Ingelheim, and Eli Lilly. He also serves on the advisory boards of AstraZeneca, Boehringer Ingelheim, Teva Pharmaceutical, Eli Lilly, Sanofi, Janssen Pharmaceuticals, Intarcia, Mylan, and GlaxoSmithKline.

Dr. Paauw and Dr. Skolnik are columnists for Family Practice News and Internal Medicine News.

M. Alexander Otto contributed to this report.

[email protected]

The options for treating type 2 diabetes without insulin have grown beyond metformin to include a long list of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists that can be taken with or without metformin. These new drugs have cardiovascular and kidney benefits and help with weight loss, but they also carry risks and, according to some experts, their costs can be prohibitively expensive.
 

Given the medical community’s long-term experience with treating patients with metformin, and metformin’s lower cost, most of the physicians interviewed for this article advise using SGLT2 inhibitors and GLP-1 receptor agonists as second-line treatments. Others said that they would prefer to use the newer drugs as first-line therapies in select high-risk patients, but prior authorization hurdles created by insurance companies make that approach too burdensome.

“The economics of U.S. health care is stacked against many of our patients with diabetes in the current era,” Robert H. Hopkins Jr., MD, said in an interview.

Even when their insurance approves the drugs, patients still may not be able to afford the copay, explained Dr. Hopkins, professor of internal medicine and pediatrics and director of the division of general internal medicine at the University of Arkansas for Medical Sciences, Little Rock. “Sometimes patients can purchase drugs at a lower cost than the copay to purchase with the ‘drug coverage’ in their insurance plan – unfortunately, this is not the case with the newer diabetes medications we are discussing here.”

“SGLT2 inhibitors and GLP-1 agonists can cost several hundred dollars a month, and insurers often balk at paying for them. They’ll say, ‘Have you tried metformin?’ ” explained endocrinologist Victor Lawrence Roberts, MD, in a interview. “We have to work with insurance companies the best we can in a stepwise fashion.”

According to Dr. Roberts, 80% of his patients with diabetes struggle with the cost of medicine in general. “They’re either underinsured or not insured or their formulary is limited.

Douglas S. Paauw, MD, agreed in an interview that the newer drugs can be problematic on the insurance front.

“For some patients they aren’t affordable, especially for the uninsured if you can’t get them on an assistance program,” said Dr. Paauw, who is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the university.

Dr. Hopkins, who is on the Internal Medicine News board, noted that “unfortunately, the treatment of type 2 diabetes in patients who cannot achieve control with metformin, diet, weight control, and exercise is a story of the ‘haves’ and the ‘have nots.’ The ‘haves’ are those who have pharmacy benefits which make access to newer agents like SGLT2 inhibitors and GLP-1 agonists a possibility.”

“Most insurance companies are now covering select SGLT2 inhibitors and GLP-1 receptor agonists for appropriate patients and those companies that currently do not will soon have to,” said Dr. Skolnik, who is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

“The outcomes [associated with use of the new drugs] are robust, the benefits are large, and are well worth the cost,” he added.
 

The side effects

While others praised these drugs for their beneficial effects, they also noted that the side effects of these drugs are serious and must be discussed with patients.

GLP-1 receptor agonists are linked to gastrointestinal symptoms, especially nausea, while SGLT2 inhibitors have been linked to kidney failure, ketoacidosis, and more. The Food and Drug Administration warned in 2018 that the SGLT2 inhibitors can cause a rare serious infection known as Fournier’s gangrene – necrotizing fasciitis of the perineum.

“We have to tell our patients to let us know right away if they get pain or swelling in the genital area,” Dr. Paauw, who is on the Internal Medicine News board, noted. “The chance that an infection could explode quickly is higher in those who take these drugs.”

Amputation risks also are associated with taking the SGLT2 inhibitor canagliflozin (Invokana). The FDA requires the manufacturer of this drug to include a black-box warning about the risk of “lower-limb amputations, most frequently of the toe and midfoot,” but also the leg. In approval trials, the risk doubled versus placebo.

These amputation risks “put a damper on some of the enthusiasm on behalf of physicians and patients ... for taking this drug,” noted Dr. Roberts, who is a professor of internal medicine at the University of Central Florida, Orlando.

While a manufacturer-funded study released last year found no link to amputations, the results weren’t powerful enough to rule out a moderately increased risk.

“[If] you are at high risk for having an amputation, we really have to take this risk very seriously,” said John B. Buse, MD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill, in a presentation about the study at the 2018 annual scientific sessions of the American Diabetes Association.
 

The benefits

Despite these risks of adverse events, most interviewed agreed that the many benefits observed in those taking SGLT2 inhibitors or GLP-1 receptor agonists make them worth prescribing, at least to those who are able to afford them.

Both SGLT2 inhibitors and GLP-1 receptor agonists appear to have significant cardiovascular benefits. A 2019 meta-­analysis and systematic review found that both drugs reduced major adverse cardiac events by about 12% (Circulation. 2019 Apr 23;139[17]:2022-31).

“They don’t cause hypoglycemia, they lower blood pressure, they don’t cause weight gain, and they might promote weight loss,” noted Dr. Paauw.

SGLT2 inhibitors also have shown signs of kidney benefits. The CREDENCE trial linked canagliflozin to a lowering of kidney disorders versus placebo (N Engl J Med. 2019 Jun 13;380[24]:2295-306). “The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% confidence interval, 0.53-0.81; P less than .001), and the relative risk of end-stage kidney disease was lower by 32% (HR, 0.68; 95% CI, 0.54-0.86; P = .002),” the trial investigators wrote.

“They showed very nicely that the drug improved the kidney function of those patients and reduced the kidney deterioration,” said Yehuda Handelsman, MD, an endocrinologist in Tarzana, Calif., who chaired the 2011 and 2015 American Association of Clinical Endocrinologists’ Comprehensive Diabetes Guidelines. The study was especially impressive, he added, because it included patients with low kidney function.

SGLT2 inhibitors’ “diuretic mechanism explains why there is a substantial reduction in heart failure hospitalizations in patients who take these drugs,” said cardiologist Marc E. Goldschmidt, MD, director of the Heart Success Program at Atlantic Health System’s Morristown (N.J.) Medical Center, in an interview. “Both the EMPA-REG Outcome and the CREDENCE trials demonstrated substantial benefit of this class of medications by showing a lower risk of cardiovascular death as well as death from any cause and a lower risk of hospitalization for heart failure."

Overall, the SGLT2 trial data have been very consistent with a benefit for cardiovascular risk reduction, particularly in regard to heart failure hospitalizations and even in potentially preventing heart failure in diabetics,” he added.

Dr. Skolnik, a columnist for Family Practice News, cited SGLT2 inhibitors and GLP-1 receptor agonists’ ability to slow renal disease progression, promote weight loss, and prevent poor cardiac outcomes.“These drugs should be used, in addition to metformin, in all patients with diabetes and vascular disease. These proven outcomes are far better than we ever were able to achieve previously and the strength of the evidence at this point is very strong,” said Dr. Skolnik. “In addition to the benefits of decreasing the development of cardiovascular disease, serious heart failure, and slowing progression of renal disease, these two classes of medication have additional benefits. Both classes help patients lose weight, which is very different from what was found with either sulfonylureas or insulin, which cause patients to gain weight. Also both the SGLT2 inhibitors and the GLP-1 RAs [receptor agonists] have a low incidence of hypoglycemia. For all these reasons, these have become important medications for us to use in primary care.”

Other recent trials offer “very powerful data” about SGLT2 inhibitors, Dr. Roberts said. That’s good news, since “our approach needs to be toward cardiovascular protection and preservation as well as managing blood sugar.”An Israeli trial, whose results were released in May 2019 at the annual meeting of the American College of Cardiology, found that, compared with other glucose-lowering drugs, taking an SGLT2 inhibitor was associated with lower risks of heart failure hospitalization and all-cause mortality (HR, 0.54; 95% CI, 0.44-0.65; P less than .001). This trial also offered a new detail: The patients gained the benefit regardless of whether their baseline left ventricular ejection fraction was preserved or reduced (J Coll Cardiol. 2019 Mar;73[9]:suppl 1). The SGLT2 inhibitors used in this trial included dapagliflozin (Farxiga) and empagliflozin (Jardiance).

In another study released this year, a subanalysis of the DECLARE-TIMI 58 trial, researchers reported that the SGLT2 inhibitor dapagliflozin reduced risks of both major adverse cardiovascular events and heart failure hospitalization in the subset of patients with type 2 diabetes and prior myocardial infarction versus controls (Circulation. 2019 May 28;139[22]:2516-27). The absolute risk reduction for major adverse cardiovascular events was 1.9% (HR, 0.81; 95% CI, 0.65-1.00; P = .046), while it was 0.6% for heart failure hospitalization (HR, 0.85; 95% CI, 0.72-1.00; P = .055).

These and other studies “speak volumes about the efficacy of managing blood sugar and addressing our biggest nemesis, which is cardiovascular disease,” Dr. Roberts said. “It’s irrefutable. The data [are] very good.”

Dr. Paauw said an SGLT2 inhibitor or GLP-1 receptor agonist is best reserved for use in select patients with cardiovascular risks and type 2 diabetes that need management beyond metformin.

For example, they might fit a 70-year-old with persistent hypertension who’s already taking a couple of blood pressure medications. “If they have another cardiovascular risk factor, the cardiovascular protection piece will be a bigger deal,” he said. Also, “it will probably help lower their blood pressure so they can avoid taking another blood pressure medicine.”

Trials of both GLP-1 receptor agonists and SGLT2 inhibitors have shown benefits “in improving [major adverse cardiac events], with the SGLT2 class showing substantial benefit in improving both heart failure and renal outcomes as well,” noted Dr. Skolnik. “It is in this context that one must address the question of whether the price of the medications are worthwhile. With such substantial benefit, there is no question in my mind that – for patients who have underlying cardiovascular illness, which includes patients with existent coronary disease, history of stroke, transient ischemic attack, or peripheral vascular disease – it is far and away worth it to prescribe these classes of medications.”

Indeed, the American Diabetes Association and the European Association for the Study of Diabetes’ most recent guidelines now call for a GLP-1 receptor agonist – instead of insulin – to be the first injectable used to treat type 2 diabetes (Diabetes Care 2018 Dec; 41[12]:2669-701).

“For the relatively small number of my patients who have been able to access and use these medications for months or longer, more have tolerated the GLP-1 agonists than SGLT2 inhibitors primarily due to urinary issues,” noted Dr. Hopkins.

Dipeptidyl peptidase–4 inhibitors are another option in patients with type 2 diabetes, but research suggests they may not be a top option for patients with cardiovascular risk. A 2018 review noted that cardiovascular outcome trials for alogliptin (Nesina), saxagliptin (Onglyza), and sitagliptin (Januvia) showed noninferiority but failed to demonstrate any superiority, compared with placebo in patients with type 2 diabetes mellitus and high cardiovascular risk (Circ Res. 2018 May 11;122[10]:1439-59).
 

The combination therapies

Many of the newer drugs are available as combinations with other types of diabetes drugs. In some cases, physicians create their own form of combination therapy by separately prescribing two or more diabetes drugs. Earlier this year, a study suggested the benefits of this kind of add-on therapy: Diabetes outcomes improved in patients who took the GLP-1 receptor agonist semaglutide and an SGLT2 inhibitor (Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587[19]30066-X).

Dr. Roberts suggested caution, however, when prescribing combination therapies. “My recommendation is always to begin with the individual medications to see if the patient tolerates the drugs and then decide which component needs to be titrated. It’s hard to titrate a combination drug, and it doesn’t leave a lot of flexibility. You never know which drug is doing what.
 

Dr. Handelsman said some patients may need to take three medications such as metformin, an SGLT2 inhibitor, and a GLP-1 receptor agonist.

“I don’t recommend using the combinations if you’re not familiar with the drugs ... These are relatively new pharmaceuticals, and most of us are on a learning curve as to how they fit into the armamentarium. If a drug is tolerated with a good response, you can certainly consider going to the combination tablets,” he added.

There is at least one drug that combines these three classes: The newly FDA-approved Qternmet XR, which combines dapagliflozin (an SGLT2 inhibitor), saxagliptin (a GLP-1 receptor agonist), and metformin. As of mid-June 2019, it was not yet available in the United States. Its sister drug Qtern, which combines dapagliflozin and saxagliptin, costs more than $500 a month with a free coupon, according to goodrx.com. In contrast, metformin is extremely inexpensive, costing just a few dollars a month for a common starting dose.
 

What about adding insulin?

“Both [SGLT2 inhibitors and GLP-1 receptor agonists] work very well with insulin,” Dr. Handelsman said. “There is a nice additive effect on the reduction of [hemoglobin] A_1c. The only caution is that, although neither SGLT2 inhibitors nor GLP-1 receptor agonists cause hypoglycemia, in combination with insulin they do increase the risk of hypoglycemia. You may have to adjust the dose of insulin.”

Dr. Hopkins warned that cost becomes an even bigger issue when you add insulin into the mix.

“When insulin comes into the discussion, we are again stuck with astronomical costs which many struggle to afford,” he explained.

Indeed, the price tag on these drugs seems to be the biggest problem physicians have with them.

“The challenges in managing patients with diabetes aren’t the risks associated with the drugs. It’s dealing with their insurers,” noted Dr. Roberts.

Dr. Hopkins, Dr. Paauw, Dr. Roberts, and Dr. Syed reported no disclosures. Dr. Buse is an investigator for Johnson and Johnson. Dr. Goldschmidt is paid to speak by Novartis. Dr. Handelsman reported research grants, consulting work, and speaker honoraria from Amgen, Gilead, Lilly, Merck, Novo Nordisk, and others. Dr Skolnik reported nonfinancial support from AstraZeneca, Boehringer Ingelheim, Sanofi, and GlaxoSmithKline and personal fees from AstraZeneca, Boehringer Ingelheim, and Eli Lilly. He also serves on the advisory boards of AstraZeneca, Boehringer Ingelheim, Teva Pharmaceutical, Eli Lilly, Sanofi, Janssen Pharmaceuticals, Intarcia, Mylan, and GlaxoSmithKline.

Dr. Paauw and Dr. Skolnik are columnists for Family Practice News and Internal Medicine News.

M. Alexander Otto contributed to this report.

[email protected]

The options for treating type 2 diabetes without insulin have grown beyond metformin to include a long list of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists that can be taken with or without metformin. These new drugs have cardiovascular and kidney benefits and help with weight loss, but they also carry risks and, according to some experts, their costs can be prohibitively expensive.
 

Given the medical community’s long-term experience with treating patients with metformin, and metformin’s lower cost, most of the physicians interviewed for this article advise using SGLT2 inhibitors and GLP-1 receptor agonists as second-line treatments. Others said that they would prefer to use the newer drugs as first-line therapies in select high-risk patients, but prior authorization hurdles created by insurance companies make that approach too burdensome.

“The economics of U.S. health care is stacked against many of our patients with diabetes in the current era,” Robert H. Hopkins Jr., MD, said in an interview.

Even when their insurance approves the drugs, patients still may not be able to afford the copay, explained Dr. Hopkins, professor of internal medicine and pediatrics and director of the division of general internal medicine at the University of Arkansas for Medical Sciences, Little Rock. “Sometimes patients can purchase drugs at a lower cost than the copay to purchase with the ‘drug coverage’ in their insurance plan – unfortunately, this is not the case with the newer diabetes medications we are discussing here.”

“SGLT2 inhibitors and GLP-1 agonists can cost several hundred dollars a month, and insurers often balk at paying for them. They’ll say, ‘Have you tried metformin?’ ” explained endocrinologist Victor Lawrence Roberts, MD, in a interview. “We have to work with insurance companies the best we can in a stepwise fashion.”

According to Dr. Roberts, 80% of his patients with diabetes struggle with the cost of medicine in general. “They’re either underinsured or not insured or their formulary is limited.

Douglas S. Paauw, MD, agreed in an interview that the newer drugs can be problematic on the insurance front.

“For some patients they aren’t affordable, especially for the uninsured if you can’t get them on an assistance program,” said Dr. Paauw, who is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the university.

Dr. Hopkins, who is on the Internal Medicine News board, noted that “unfortunately, the treatment of type 2 diabetes in patients who cannot achieve control with metformin, diet, weight control, and exercise is a story of the ‘haves’ and the ‘have nots.’ The ‘haves’ are those who have pharmacy benefits which make access to newer agents like SGLT2 inhibitors and GLP-1 agonists a possibility.”

“Most insurance companies are now covering select SGLT2 inhibitors and GLP-1 receptor agonists for appropriate patients and those companies that currently do not will soon have to,” said Dr. Skolnik, who is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

“The outcomes [associated with use of the new drugs] are robust, the benefits are large, and are well worth the cost,” he added.
 

The side effects

While others praised these drugs for their beneficial effects, they also noted that the side effects of these drugs are serious and must be discussed with patients.

GLP-1 receptor agonists are linked to gastrointestinal symptoms, especially nausea, while SGLT2 inhibitors have been linked to kidney failure, ketoacidosis, and more. The Food and Drug Administration warned in 2018 that the SGLT2 inhibitors can cause a rare serious infection known as Fournier’s gangrene – necrotizing fasciitis of the perineum.

“We have to tell our patients to let us know right away if they get pain or swelling in the genital area,” Dr. Paauw, who is on the Internal Medicine News board, noted. “The chance that an infection could explode quickly is higher in those who take these drugs.”

Amputation risks also are associated with taking the SGLT2 inhibitor canagliflozin (Invokana). The FDA requires the manufacturer of this drug to include a black-box warning about the risk of “lower-limb amputations, most frequently of the toe and midfoot,” but also the leg. In approval trials, the risk doubled versus placebo.

These amputation risks “put a damper on some of the enthusiasm on behalf of physicians and patients ... for taking this drug,” noted Dr. Roberts, who is a professor of internal medicine at the University of Central Florida, Orlando.

While a manufacturer-funded study released last year found no link to amputations, the results weren’t powerful enough to rule out a moderately increased risk.

“[If] you are at high risk for having an amputation, we really have to take this risk very seriously,” said John B. Buse, MD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill, in a presentation about the study at the 2018 annual scientific sessions of the American Diabetes Association.
 

The benefits

Despite these risks of adverse events, most interviewed agreed that the many benefits observed in those taking SGLT2 inhibitors or GLP-1 receptor agonists make them worth prescribing, at least to those who are able to afford them.

Both SGLT2 inhibitors and GLP-1 receptor agonists appear to have significant cardiovascular benefits. A 2019 meta-­analysis and systematic review found that both drugs reduced major adverse cardiac events by about 12% (Circulation. 2019 Apr 23;139[17]:2022-31).

“They don’t cause hypoglycemia, they lower blood pressure, they don’t cause weight gain, and they might promote weight loss,” noted Dr. Paauw.

SGLT2 inhibitors also have shown signs of kidney benefits. The CREDENCE trial linked canagliflozin to a lowering of kidney disorders versus placebo (N Engl J Med. 2019 Jun 13;380[24]:2295-306). “The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% confidence interval, 0.53-0.81; P less than .001), and the relative risk of end-stage kidney disease was lower by 32% (HR, 0.68; 95% CI, 0.54-0.86; P = .002),” the trial investigators wrote.

“They showed very nicely that the drug improved the kidney function of those patients and reduced the kidney deterioration,” said Yehuda Handelsman, MD, an endocrinologist in Tarzana, Calif., who chaired the 2011 and 2015 American Association of Clinical Endocrinologists’ Comprehensive Diabetes Guidelines. The study was especially impressive, he added, because it included patients with low kidney function.

SGLT2 inhibitors’ “diuretic mechanism explains why there is a substantial reduction in heart failure hospitalizations in patients who take these drugs,” said cardiologist Marc E. Goldschmidt, MD, director of the Heart Success Program at Atlantic Health System’s Morristown (N.J.) Medical Center, in an interview. “Both the EMPA-REG Outcome and the CREDENCE trials demonstrated substantial benefit of this class of medications by showing a lower risk of cardiovascular death as well as death from any cause and a lower risk of hospitalization for heart failure."

Overall, the SGLT2 trial data have been very consistent with a benefit for cardiovascular risk reduction, particularly in regard to heart failure hospitalizations and even in potentially preventing heart failure in diabetics,” he added.

Dr. Skolnik, a columnist for Family Practice News, cited SGLT2 inhibitors and GLP-1 receptor agonists’ ability to slow renal disease progression, promote weight loss, and prevent poor cardiac outcomes.“These drugs should be used, in addition to metformin, in all patients with diabetes and vascular disease. These proven outcomes are far better than we ever were able to achieve previously and the strength of the evidence at this point is very strong,” said Dr. Skolnik. “In addition to the benefits of decreasing the development of cardiovascular disease, serious heart failure, and slowing progression of renal disease, these two classes of medication have additional benefits. Both classes help patients lose weight, which is very different from what was found with either sulfonylureas or insulin, which cause patients to gain weight. Also both the SGLT2 inhibitors and the GLP-1 RAs [receptor agonists] have a low incidence of hypoglycemia. For all these reasons, these have become important medications for us to use in primary care.”

Other recent trials offer “very powerful data” about SGLT2 inhibitors, Dr. Roberts said. That’s good news, since “our approach needs to be toward cardiovascular protection and preservation as well as managing blood sugar.”An Israeli trial, whose results were released in May 2019 at the annual meeting of the American College of Cardiology, found that, compared with other glucose-lowering drugs, taking an SGLT2 inhibitor was associated with lower risks of heart failure hospitalization and all-cause mortality (HR, 0.54; 95% CI, 0.44-0.65; P less than .001). This trial also offered a new detail: The patients gained the benefit regardless of whether their baseline left ventricular ejection fraction was preserved or reduced (J Coll Cardiol. 2019 Mar;73[9]:suppl 1). The SGLT2 inhibitors used in this trial included dapagliflozin (Farxiga) and empagliflozin (Jardiance).

In another study released this year, a subanalysis of the DECLARE-TIMI 58 trial, researchers reported that the SGLT2 inhibitor dapagliflozin reduced risks of both major adverse cardiovascular events and heart failure hospitalization in the subset of patients with type 2 diabetes and prior myocardial infarction versus controls (Circulation. 2019 May 28;139[22]:2516-27). The absolute risk reduction for major adverse cardiovascular events was 1.9% (HR, 0.81; 95% CI, 0.65-1.00; P = .046), while it was 0.6% for heart failure hospitalization (HR, 0.85; 95% CI, 0.72-1.00; P = .055).

These and other studies “speak volumes about the efficacy of managing blood sugar and addressing our biggest nemesis, which is cardiovascular disease,” Dr. Roberts said. “It’s irrefutable. The data [are] very good.”

Dr. Paauw said an SGLT2 inhibitor or GLP-1 receptor agonist is best reserved for use in select patients with cardiovascular risks and type 2 diabetes that need management beyond metformin.

For example, they might fit a 70-year-old with persistent hypertension who’s already taking a couple of blood pressure medications. “If they have another cardiovascular risk factor, the cardiovascular protection piece will be a bigger deal,” he said. Also, “it will probably help lower their blood pressure so they can avoid taking another blood pressure medicine.”

Trials of both GLP-1 receptor agonists and SGLT2 inhibitors have shown benefits “in improving [major adverse cardiac events], with the SGLT2 class showing substantial benefit in improving both heart failure and renal outcomes as well,” noted Dr. Skolnik. “It is in this context that one must address the question of whether the price of the medications are worthwhile. With such substantial benefit, there is no question in my mind that – for patients who have underlying cardiovascular illness, which includes patients with existent coronary disease, history of stroke, transient ischemic attack, or peripheral vascular disease – it is far and away worth it to prescribe these classes of medications.”

Indeed, the American Diabetes Association and the European Association for the Study of Diabetes’ most recent guidelines now call for a GLP-1 receptor agonist – instead of insulin – to be the first injectable used to treat type 2 diabetes (Diabetes Care 2018 Dec; 41[12]:2669-701).

“For the relatively small number of my patients who have been able to access and use these medications for months or longer, more have tolerated the GLP-1 agonists than SGLT2 inhibitors primarily due to urinary issues,” noted Dr. Hopkins.

Dipeptidyl peptidase–4 inhibitors are another option in patients with type 2 diabetes, but research suggests they may not be a top option for patients with cardiovascular risk. A 2018 review noted that cardiovascular outcome trials for alogliptin (Nesina), saxagliptin (Onglyza), and sitagliptin (Januvia) showed noninferiority but failed to demonstrate any superiority, compared with placebo in patients with type 2 diabetes mellitus and high cardiovascular risk (Circ Res. 2018 May 11;122[10]:1439-59).
 

The combination therapies

Many of the newer drugs are available as combinations with other types of diabetes drugs. In some cases, physicians create their own form of combination therapy by separately prescribing two or more diabetes drugs. Earlier this year, a study suggested the benefits of this kind of add-on therapy: Diabetes outcomes improved in patients who took the GLP-1 receptor agonist semaglutide and an SGLT2 inhibitor (Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587[19]30066-X).

Dr. Roberts suggested caution, however, when prescribing combination therapies. “My recommendation is always to begin with the individual medications to see if the patient tolerates the drugs and then decide which component needs to be titrated. It’s hard to titrate a combination drug, and it doesn’t leave a lot of flexibility. You never know which drug is doing what.
 

Dr. Handelsman said some patients may need to take three medications such as metformin, an SGLT2 inhibitor, and a GLP-1 receptor agonist.

“I don’t recommend using the combinations if you’re not familiar with the drugs ... These are relatively new pharmaceuticals, and most of us are on a learning curve as to how they fit into the armamentarium. If a drug is tolerated with a good response, you can certainly consider going to the combination tablets,” he added.

There is at least one drug that combines these three classes: The newly FDA-approved Qternmet XR, which combines dapagliflozin (an SGLT2 inhibitor), saxagliptin (a GLP-1 receptor agonist), and metformin. As of mid-June 2019, it was not yet available in the United States. Its sister drug Qtern, which combines dapagliflozin and saxagliptin, costs more than $500 a month with a free coupon, according to goodrx.com. In contrast, metformin is extremely inexpensive, costing just a few dollars a month for a common starting dose.
 

What about adding insulin?

“Both [SGLT2 inhibitors and GLP-1 receptor agonists] work very well with insulin,” Dr. Handelsman said. “There is a nice additive effect on the reduction of [hemoglobin] A_1c. The only caution is that, although neither SGLT2 inhibitors nor GLP-1 receptor agonists cause hypoglycemia, in combination with insulin they do increase the risk of hypoglycemia. You may have to adjust the dose of insulin.”

Dr. Hopkins warned that cost becomes an even bigger issue when you add insulin into the mix.

“When insulin comes into the discussion, we are again stuck with astronomical costs which many struggle to afford,” he explained.

Indeed, the price tag on these drugs seems to be the biggest problem physicians have with them.

“The challenges in managing patients with diabetes aren’t the risks associated with the drugs. It’s dealing with their insurers,” noted Dr. Roberts.

Dr. Hopkins, Dr. Paauw, Dr. Roberts, and Dr. Syed reported no disclosures. Dr. Buse is an investigator for Johnson and Johnson. Dr. Goldschmidt is paid to speak by Novartis. Dr. Handelsman reported research grants, consulting work, and speaker honoraria from Amgen, Gilead, Lilly, Merck, Novo Nordisk, and others. Dr Skolnik reported nonfinancial support from AstraZeneca, Boehringer Ingelheim, Sanofi, and GlaxoSmithKline and personal fees from AstraZeneca, Boehringer Ingelheim, and Eli Lilly. He also serves on the advisory boards of AstraZeneca, Boehringer Ingelheim, Teva Pharmaceutical, Eli Lilly, Sanofi, Janssen Pharmaceuticals, Intarcia, Mylan, and GlaxoSmithKline.

Dr. Paauw and Dr. Skolnik are columnists for Family Practice News and Internal Medicine News.

M. Alexander Otto contributed to this report.

[email protected]

PHILADELPHIA – A surprisingly large number of patients with migraine who first seek care for migraine in a primary care setting receive an initial migraine diagnosis from a neurologist, said Alice R. Pressman, PhD at the annual meeting of the American Headache Society.

Dr. Pressman, executive director of research, development, and dissemination for Sutter Health, and her research colleagues analyzed data from primary care patients who sought care for migraine in the Sutter Health healthcare network in Northern California. They found that women were 10% more likely than men to consult a neurologist and that Asian patients had a longer time to a first neurology encounter for migraine, compared with Caucasian patients.

“Those who sought care from neurology had more severe migraine symptomology, disability, and comorbidities,” the researchers reported. Furthermore, patients with migraine seen by neurologists were more likely to receive prescriptions for acute and preventive migraine medications, compared with patients only seen by primary care physicians.

The study, known as the Migraine Signature Study, used electronic health records (EHR) and patient-reported questionnaire data to examine the clinical experiences and care of patients with migraine.

The primary care population consisted of 1.4 million adults with at least one office visit to primary care in 2013-2017. Using the validated Migraine Probability Algorithm, the researchers identified approximately 94,000 patients who sought care for migraine.

The investigators also invited 38,536 patients to complete an online survey about migraine criteria, symptomology, health resource utilization, and patient-reported outcomes such as disability, acute treatment optimization, cutaneous allodynia, depression, anxiety, and posttraumatic stress disorder (PTSD).

Of the patients who sought care for migraine, 72,624 patients did not receive migraine care from neurology, and 21,525 did.

Patients with migraine care from a neurologist were more likely to have at least one acute migraine medication order (89.4% vs. 80.6%), at least one preventive migraine medication order (78.6% vs. 49.1%), and any migraine medication order (95.3% vs. 85.9%). In addition, those with at least one medication order in the primary care setting had fewer orders per person per year, compared with those with at least one medication order in the neurology setting (1.1 vs. 1.6).

About one-third of the patients who sought care for migraine had no migraine encounters in the first 12 months of the study. Of the more than 33,000 patients with first migraine consults, approximately two-thirds did not receive a neurology consultation during the study and received their migraine diagnosis in the primary care setting.

Of the 31% of patients with first migraine consults in primary care who later had a neurology consult, two-thirds received a migraine diagnosis from neurology. “The high rate of initial migraine diagnosis within neurology was surprising among this sample with primary care encounters first,” the researchers said.

The investigators also examined patient-reported outcomes from 391 respondents who received migraine care from neurology and 399 respondents who received migraine care from primary care. “Patients who consulted a neurologist were likely to report moderate-to-severe disability, poor acute treatment optimization, and major depression,” they said. “Allodynia, anxiety, and PTSD did not differ by type of provider.”

Confounding may have influenced the results, and the researchers plan to assess factors such as headache frequency and severity using patient-reported survey data in future analyses.

The Migraine Signature Study was supported by Amgen, Inc.

[email protected]

PHILADELPHIA – A surprisingly large number of patients with migraine who first seek care for migraine in a primary care setting receive an initial migraine diagnosis from a neurologist, said Alice R. Pressman, PhD at the annual meeting of the American Headache Society.

Dr. Pressman, executive director of research, development, and dissemination for Sutter Health, and her research colleagues analyzed data from primary care patients who sought care for migraine in the Sutter Health healthcare network in Northern California. They found that women were 10% more likely than men to consult a neurologist and that Asian patients had a longer time to a first neurology encounter for migraine, compared with Caucasian patients.

“Those who sought care from neurology had more severe migraine symptomology, disability, and comorbidities,” the researchers reported. Furthermore, patients with migraine seen by neurologists were more likely to receive prescriptions for acute and preventive migraine medications, compared with patients only seen by primary care physicians.

The study, known as the Migraine Signature Study, used electronic health records (EHR) and patient-reported questionnaire data to examine the clinical experiences and care of patients with migraine.

The primary care population consisted of 1.4 million adults with at least one office visit to primary care in 2013-2017. Using the validated Migraine Probability Algorithm, the researchers identified approximately 94,000 patients who sought care for migraine.

The investigators also invited 38,536 patients to complete an online survey about migraine criteria, symptomology, health resource utilization, and patient-reported outcomes such as disability, acute treatment optimization, cutaneous allodynia, depression, anxiety, and posttraumatic stress disorder (PTSD).

Of the patients who sought care for migraine, 72,624 patients did not receive migraine care from neurology, and 21,525 did.

Patients with migraine care from a neurologist were more likely to have at least one acute migraine medication order (89.4% vs. 80.6%), at least one preventive migraine medication order (78.6% vs. 49.1%), and any migraine medication order (95.3% vs. 85.9%). In addition, those with at least one medication order in the primary care setting had fewer orders per person per year, compared with those with at least one medication order in the neurology setting (1.1 vs. 1.6).

About one-third of the patients who sought care for migraine had no migraine encounters in the first 12 months of the study. Of the more than 33,000 patients with first migraine consults, approximately two-thirds did not receive a neurology consultation during the study and received their migraine diagnosis in the primary care setting.

Of the 31% of patients with first migraine consults in primary care who later had a neurology consult, two-thirds received a migraine diagnosis from neurology. “The high rate of initial migraine diagnosis within neurology was surprising among this sample with primary care encounters first,” the researchers said.

The investigators also examined patient-reported outcomes from 391 respondents who received migraine care from neurology and 399 respondents who received migraine care from primary care. “Patients who consulted a neurologist were likely to report moderate-to-severe disability, poor acute treatment optimization, and major depression,” they said. “Allodynia, anxiety, and PTSD did not differ by type of provider.”

Confounding may have influenced the results, and the researchers plan to assess factors such as headache frequency and severity using patient-reported survey data in future analyses.

The Migraine Signature Study was supported by Amgen, Inc.

[email protected]

PHILADELPHIA – A surprisingly large number of patients with migraine who first seek care for migraine in a primary care setting receive an initial migraine diagnosis from a neurologist, said Alice R. Pressman, PhD at the annual meeting of the American Headache Society.

Dr. Pressman, executive director of research, development, and dissemination for Sutter Health, and her research colleagues analyzed data from primary care patients who sought care for migraine in the Sutter Health healthcare network in Northern California. They found that women were 10% more likely than men to consult a neurologist and that Asian patients had a longer time to a first neurology encounter for migraine, compared with Caucasian patients.

“Those who sought care from neurology had more severe migraine symptomology, disability, and comorbidities,” the researchers reported. Furthermore, patients with migraine seen by neurologists were more likely to receive prescriptions for acute and preventive migraine medications, compared with patients only seen by primary care physicians.

The study, known as the Migraine Signature Study, used electronic health records (EHR) and patient-reported questionnaire data to examine the clinical experiences and care of patients with migraine.

The primary care population consisted of 1.4 million adults with at least one office visit to primary care in 2013-2017. Using the validated Migraine Probability Algorithm, the researchers identified approximately 94,000 patients who sought care for migraine.

The investigators also invited 38,536 patients to complete an online survey about migraine criteria, symptomology, health resource utilization, and patient-reported outcomes such as disability, acute treatment optimization, cutaneous allodynia, depression, anxiety, and posttraumatic stress disorder (PTSD).

Of the patients who sought care for migraine, 72,624 patients did not receive migraine care from neurology, and 21,525 did.

Patients with migraine care from a neurologist were more likely to have at least one acute migraine medication order (89.4% vs. 80.6%), at least one preventive migraine medication order (78.6% vs. 49.1%), and any migraine medication order (95.3% vs. 85.9%). In addition, those with at least one medication order in the primary care setting had fewer orders per person per year, compared with those with at least one medication order in the neurology setting (1.1 vs. 1.6).

About one-third of the patients who sought care for migraine had no migraine encounters in the first 12 months of the study. Of the more than 33,000 patients with first migraine consults, approximately two-thirds did not receive a neurology consultation during the study and received their migraine diagnosis in the primary care setting.

Of the 31% of patients with first migraine consults in primary care who later had a neurology consult, two-thirds received a migraine diagnosis from neurology. “The high rate of initial migraine diagnosis within neurology was surprising among this sample with primary care encounters first,” the researchers said.

The investigators also examined patient-reported outcomes from 391 respondents who received migraine care from neurology and 399 respondents who received migraine care from primary care. “Patients who consulted a neurologist were likely to report moderate-to-severe disability, poor acute treatment optimization, and major depression,” they said. “Allodynia, anxiety, and PTSD did not differ by type of provider.”

Confounding may have influenced the results, and the researchers plan to assess factors such as headache frequency and severity using patient-reported survey data in future analyses.

The Migraine Signature Study was supported by Amgen, Inc.

[email protected]

In a phase 3, active comparator controlled trial, treatment with risankizumab led to better skin clearance than treatment with adalimumab in patients with moderate-to-severe plaque psoriasis. Results of the IMMvent trial were published online ahead of print July 4 in the Lancet.

Risankizumab targets the p19 subunit of the cytokine IL-23. Selectivity for p19 has the potential to be safer than some other approaches that target the p40 subunit, because p19 is specific to IL-23, and many immune defense processes can function without IL-23. The p40 subunit is shared with IL-12, and blocking it can therefore lead to off-target effects.

Risankizumab was previously shown to have superior safety and efficacy over ustekinumab, which inhibits a subunit shared by IL-23 and IL-12 (Gordon KB et al. Lancet. 2018;392[10148]:650-61). Adalimumab is a TNF-alpha inhibitor that is frequently used to treat psoriasis, and which became available in biosimilar form in Europe in 2018.

The researchers randomized 605 adult patients from 66 sites in 11 countries to receive either risankizumab or adalimumab. The first phase (Part A) of the trial lasted up to 16 weeks, and tested the general superiority of risankizumab over adalimumab. The second phase (Part B), from week 16 to 44, evaluated the efficacy of risankizumab in participants who experienced an intermediate response, defined as Psoriasis Area and Severity Index (PASI) score of 50-90.

At the start of Part B, subjects initially receiving adalimumab who had at least a 90% improvement in PASI stayed on adalimumab (PASI 90), while those who had less than 50% improvement in PASI were switched to risankizumab. The remaining intermediate responders (PASI 50-90) were re-randomized to continue adalimumab or switch to risankizumab. All subjects initially randomized to risankizumab continued risankizumab during part B.

At the end of Part A, 72% of the risankizumab group achieved PASI 90, compared with 47% in the adalimumab group (p < 0.0001). A total of 84% in the risankizumab group had a static Physician’s Global Assessment (sPGA) score of 0 or 1 at the end of Part A, compared with 60% in the adalimumab group (p < 0.0001).

During Part B, among intermediate adalimumab responders, 66% of those switched to risankizumab achieved PASI 90, compared with 21% of continued on adalimumab (p < 0.0001).

In Part A, 56% of patients taking risankizumab experienced an adverse event, as did 57% of those taking adalimumab. Among adalimumab intermediate responders, 75% of those who switched to risankizumab during Part B had an adverse event, compared with 66% of those who continued adalimumab.

SOURCE: Reich K, et al. Lancet 2019, July 4 .

In a phase 3, active comparator controlled trial, treatment with risankizumab led to better skin clearance than treatment with adalimumab in patients with moderate-to-severe plaque psoriasis. Results of the IMMvent trial were published online ahead of print July 4 in the Lancet.

Risankizumab targets the p19 subunit of the cytokine IL-23. Selectivity for p19 has the potential to be safer than some other approaches that target the p40 subunit, because p19 is specific to IL-23, and many immune defense processes can function without IL-23. The p40 subunit is shared with IL-12, and blocking it can therefore lead to off-target effects.

Risankizumab was previously shown to have superior safety and efficacy over ustekinumab, which inhibits a subunit shared by IL-23 and IL-12 (Gordon KB et al. Lancet. 2018;392[10148]:650-61). Adalimumab is a TNF-alpha inhibitor that is frequently used to treat psoriasis, and which became available in biosimilar form in Europe in 2018.

The researchers randomized 605 adult patients from 66 sites in 11 countries to receive either risankizumab or adalimumab. The first phase (Part A) of the trial lasted up to 16 weeks, and tested the general superiority of risankizumab over adalimumab. The second phase (Part B), from week 16 to 44, evaluated the efficacy of risankizumab in participants who experienced an intermediate response, defined as Psoriasis Area and Severity Index (PASI) score of 50-90.

At the start of Part B, subjects initially receiving adalimumab who had at least a 90% improvement in PASI stayed on adalimumab (PASI 90), while those who had less than 50% improvement in PASI were switched to risankizumab. The remaining intermediate responders (PASI 50-90) were re-randomized to continue adalimumab or switch to risankizumab. All subjects initially randomized to risankizumab continued risankizumab during part B.

At the end of Part A, 72% of the risankizumab group achieved PASI 90, compared with 47% in the adalimumab group (p < 0.0001). A total of 84% in the risankizumab group had a static Physician’s Global Assessment (sPGA) score of 0 or 1 at the end of Part A, compared with 60% in the adalimumab group (p < 0.0001).

During Part B, among intermediate adalimumab responders, 66% of those switched to risankizumab achieved PASI 90, compared with 21% of continued on adalimumab (p < 0.0001).

In Part A, 56% of patients taking risankizumab experienced an adverse event, as did 57% of those taking adalimumab. Among adalimumab intermediate responders, 75% of those who switched to risankizumab during Part B had an adverse event, compared with 66% of those who continued adalimumab.

SOURCE: Reich K, et al. Lancet 2019, July 4 .

In a phase 3, active comparator controlled trial, treatment with risankizumab led to better skin clearance than treatment with adalimumab in patients with moderate-to-severe plaque psoriasis. Results of the IMMvent trial were published online ahead of print July 4 in the Lancet.

Risankizumab targets the p19 subunit of the cytokine IL-23. Selectivity for p19 has the potential to be safer than some other approaches that target the p40 subunit, because p19 is specific to IL-23, and many immune defense processes can function without IL-23. The p40 subunit is shared with IL-12, and blocking it can therefore lead to off-target effects.

Risankizumab was previously shown to have superior safety and efficacy over ustekinumab, which inhibits a subunit shared by IL-23 and IL-12 (Gordon KB et al. Lancet. 2018;392[10148]:650-61). Adalimumab is a TNF-alpha inhibitor that is frequently used to treat psoriasis, and which became available in biosimilar form in Europe in 2018.

The researchers randomized 605 adult patients from 66 sites in 11 countries to receive either risankizumab or adalimumab. The first phase (Part A) of the trial lasted up to 16 weeks, and tested the general superiority of risankizumab over adalimumab. The second phase (Part B), from week 16 to 44, evaluated the efficacy of risankizumab in participants who experienced an intermediate response, defined as Psoriasis Area and Severity Index (PASI) score of 50-90.

At the start of Part B, subjects initially receiving adalimumab who had at least a 90% improvement in PASI stayed on adalimumab (PASI 90), while those who had less than 50% improvement in PASI were switched to risankizumab. The remaining intermediate responders (PASI 50-90) were re-randomized to continue adalimumab or switch to risankizumab. All subjects initially randomized to risankizumab continued risankizumab during part B.

At the end of Part A, 72% of the risankizumab group achieved PASI 90, compared with 47% in the adalimumab group (p < 0.0001). A total of 84% in the risankizumab group had a static Physician’s Global Assessment (sPGA) score of 0 or 1 at the end of Part A, compared with 60% in the adalimumab group (p < 0.0001).

During Part B, among intermediate adalimumab responders, 66% of those switched to risankizumab achieved PASI 90, compared with 21% of continued on adalimumab (p < 0.0001).

In Part A, 56% of patients taking risankizumab experienced an adverse event, as did 57% of those taking adalimumab. Among adalimumab intermediate responders, 75% of those who switched to risankizumab during Part B had an adverse event, compared with 66% of those who continued adalimumab.

SOURCE: Reich K, et al. Lancet 2019, July 4 .

PHILADELPHIA – Mindfulness-based cognitive therapy tailored for migraine may reduce migraine-related disability, even as the number of headache days and pain intensity remain unchanged, according to randomized clinical trial results.

“The fact that people can improve how they live their daily life even with the same amount of headache days and the same pain intensity is remarkable,” said study investigator Elizabeth K. Seng, PhD, associate professor of psychology at Yeshiva University and research associate professor of neurology at Albert Einstein College of Medicine, both in New York. “I think this gives us a little bit of a clue about when to use these kinds of treatments.”

Dr. Seng presented findings from the phase 2b pilot trial at the annual meeting of the American Headache Society.

To study the efficacy of mindfulness-based cognitive therapy for migraine, Dr. Seng and her research colleagues recruited participants with migraine in the New York City area between 2015 and 2018. In all, 60 patients were randomized to receive 8 weekly individual 75-minute mindfulness-based cognitive therapy for migraine sessions or 8 weeks on a wait list with treatment as usual.

Primary outcomes were Month 0 to Month 4 changes in perceived disability, measured using the Henry Ford Disability Inventory (HDI) and functional disability measured using the Migraine Disability Assessment Scale (MIDAS). Secondary outcomes included changes in headache days per 30 days and headache pain intensity.

Participants had a mean age of about 40 years, about 92% were women, and approximately half of the patients had chronic migraine. Participants had an average baseline HDI of 51.4, and 83.3% had MIDAS scores indicating severe disability. Patients averaged 10.4 headache attack days per month, and mean headache attack severity on a 0-10 scale was 6.2. Attrition did not significantly differ between the mindfulness-based cognitive therapy and control groups.

Patients who received mindfulness-based cognitive therapy for migraine experienced an approximately 15-point reduction on the HDI scale at 4 months, whereas wait-listed patients did not experience much of a change, Dr. Seng said. The difference between groups was statistically significant.

At 4 months, a smaller proportion of patients in the mindfulness-based cognitive therapy group had a MIDAS score of 21 or greater, but the difference between groups was not statistically significant. The data indicate a large effect that the study was underpowered to detect, Dr. Seng said.

A planned subgroup analysis found that mindfulness-based cognitive therapy produced changes in disability that were greater in patients with episodic migraine, compared with patients with chronic migraine. A reduction in MIDAS scores was statistically significant among patients with episodic migraine.

During the trial, one patient experienced increased headache frequency and intensity and changed their preventive treatment regimen, which investigators considered unrelated to mindfulness-based cognitive therapy. In addition, one patient experienced flooding – a vivid recollection of a traumatic event – which is an expected effect of meditation and relaxation therapy, Dr. Seng said. The patient completed the study and was satisfied with the mindfulness-based cognitive therapy training, she said.

“Preliminary evidence suggests that mindfulness-based cognitive therapy could be recommended to reduce headache-related disability in people with episodic migraine or people who have some kind of effective prevention on board, but they are still experiencing high levels of disability,” Dr. Seng said.

Although flooding may occur in patients with a trauma history who use meditation and relaxation, the techniques still may be useful, Dr. Seng said. “In the VA setting, we use meditation and relaxation all the time. But it helps to forewarn patients that they might experience distressful flooding and [to provide] techniques that they can use to reduce the impact of that.”

[email protected]

PHILADELPHIA – Mindfulness-based cognitive therapy tailored for migraine may reduce migraine-related disability, even as the number of headache days and pain intensity remain unchanged, according to randomized clinical trial results.

“The fact that people can improve how they live their daily life even with the same amount of headache days and the same pain intensity is remarkable,” said study investigator Elizabeth K. Seng, PhD, associate professor of psychology at Yeshiva University and research associate professor of neurology at Albert Einstein College of Medicine, both in New York. “I think this gives us a little bit of a clue about when to use these kinds of treatments.”

Dr. Seng presented findings from the phase 2b pilot trial at the annual meeting of the American Headache Society.

To study the efficacy of mindfulness-based cognitive therapy for migraine, Dr. Seng and her research colleagues recruited participants with migraine in the New York City area between 2015 and 2018. In all, 60 patients were randomized to receive 8 weekly individual 75-minute mindfulness-based cognitive therapy for migraine sessions or 8 weeks on a wait list with treatment as usual.

Primary outcomes were Month 0 to Month 4 changes in perceived disability, measured using the Henry Ford Disability Inventory (HDI) and functional disability measured using the Migraine Disability Assessment Scale (MIDAS). Secondary outcomes included changes in headache days per 30 days and headache pain intensity.

Participants had a mean age of about 40 years, about 92% were women, and approximately half of the patients had chronic migraine. Participants had an average baseline HDI of 51.4, and 83.3% had MIDAS scores indicating severe disability. Patients averaged 10.4 headache attack days per month, and mean headache attack severity on a 0-10 scale was 6.2. Attrition did not significantly differ between the mindfulness-based cognitive therapy and control groups.

Patients who received mindfulness-based cognitive therapy for migraine experienced an approximately 15-point reduction on the HDI scale at 4 months, whereas wait-listed patients did not experience much of a change, Dr. Seng said. The difference between groups was statistically significant.

At 4 months, a smaller proportion of patients in the mindfulness-based cognitive therapy group had a MIDAS score of 21 or greater, but the difference between groups was not statistically significant. The data indicate a large effect that the study was underpowered to detect, Dr. Seng said.

A planned subgroup analysis found that mindfulness-based cognitive therapy produced changes in disability that were greater in patients with episodic migraine, compared with patients with chronic migraine. A reduction in MIDAS scores was statistically significant among patients with episodic migraine.

During the trial, one patient experienced increased headache frequency and intensity and changed their preventive treatment regimen, which investigators considered unrelated to mindfulness-based cognitive therapy. In addition, one patient experienced flooding – a vivid recollection of a traumatic event – which is an expected effect of meditation and relaxation therapy, Dr. Seng said. The patient completed the study and was satisfied with the mindfulness-based cognitive therapy training, she said.

“Preliminary evidence suggests that mindfulness-based cognitive therapy could be recommended to reduce headache-related disability in people with episodic migraine or people who have some kind of effective prevention on board, but they are still experiencing high levels of disability,” Dr. Seng said.

Although flooding may occur in patients with a trauma history who use meditation and relaxation, the techniques still may be useful, Dr. Seng said. “In the VA setting, we use meditation and relaxation all the time. But it helps to forewarn patients that they might experience distressful flooding and [to provide] techniques that they can use to reduce the impact of that.”

[email protected]

PHILADELPHIA – Mindfulness-based cognitive therapy tailored for migraine may reduce migraine-related disability, even as the number of headache days and pain intensity remain unchanged, according to randomized clinical trial results.

“The fact that people can improve how they live their daily life even with the same amount of headache days and the same pain intensity is remarkable,” said study investigator Elizabeth K. Seng, PhD, associate professor of psychology at Yeshiva University and research associate professor of neurology at Albert Einstein College of Medicine, both in New York. “I think this gives us a little bit of a clue about when to use these kinds of treatments.”

Dr. Seng presented findings from the phase 2b pilot trial at the annual meeting of the American Headache Society.

To study the efficacy of mindfulness-based cognitive therapy for migraine, Dr. Seng and her research colleagues recruited participants with migraine in the New York City area between 2015 and 2018. In all, 60 patients were randomized to receive 8 weekly individual 75-minute mindfulness-based cognitive therapy for migraine sessions or 8 weeks on a wait list with treatment as usual.

Primary outcomes were Month 0 to Month 4 changes in perceived disability, measured using the Henry Ford Disability Inventory (HDI) and functional disability measured using the Migraine Disability Assessment Scale (MIDAS). Secondary outcomes included changes in headache days per 30 days and headache pain intensity.

Participants had a mean age of about 40 years, about 92% were women, and approximately half of the patients had chronic migraine. Participants had an average baseline HDI of 51.4, and 83.3% had MIDAS scores indicating severe disability. Patients averaged 10.4 headache attack days per month, and mean headache attack severity on a 0-10 scale was 6.2. Attrition did not significantly differ between the mindfulness-based cognitive therapy and control groups.

Patients who received mindfulness-based cognitive therapy for migraine experienced an approximately 15-point reduction on the HDI scale at 4 months, whereas wait-listed patients did not experience much of a change, Dr. Seng said. The difference between groups was statistically significant.

At 4 months, a smaller proportion of patients in the mindfulness-based cognitive therapy group had a MIDAS score of 21 or greater, but the difference between groups was not statistically significant. The data indicate a large effect that the study was underpowered to detect, Dr. Seng said.

A planned subgroup analysis found that mindfulness-based cognitive therapy produced changes in disability that were greater in patients with episodic migraine, compared with patients with chronic migraine. A reduction in MIDAS scores was statistically significant among patients with episodic migraine.

During the trial, one patient experienced increased headache frequency and intensity and changed their preventive treatment regimen, which investigators considered unrelated to mindfulness-based cognitive therapy. In addition, one patient experienced flooding – a vivid recollection of a traumatic event – which is an expected effect of meditation and relaxation therapy, Dr. Seng said. The patient completed the study and was satisfied with the mindfulness-based cognitive therapy training, she said.

“Preliminary evidence suggests that mindfulness-based cognitive therapy could be recommended to reduce headache-related disability in people with episodic migraine or people who have some kind of effective prevention on board, but they are still experiencing high levels of disability,” Dr. Seng said.

Although flooding may occur in patients with a trauma history who use meditation and relaxation, the techniques still may be useful, Dr. Seng said. “In the VA setting, we use meditation and relaxation all the time. But it helps to forewarn patients that they might experience distressful flooding and [to provide] techniques that they can use to reduce the impact of that.”

[email protected]

PHILADELPHIA – Patients with a history of migraine who underwent any type of surgery and then received a perioperative prescription for a headache abortive agent such as a triptan had 37% fewer readmissions for pain during the 30 days following surgery compared with patients who did not receive a migraine abortive prescription, according to an observational review of nearly 22,000 migraine patients from the Boston area.

Mitchel L. Zoler/MDedge News

While this statistically significant observational association must be viewed with caution, it provides compelling evidence for clinicians to prescribe a migraine abortive agent to migraineurs soon after surgery so that patients have these drugs handy if a migraine strikes, a possibility made likely by the stress and disruption of surgery, Katharina Platzbecker, MD, said at the annual meeting of the American Headache Society.

Postoperative migraine patients who received an abortive prescription specifically for a triptan or ergotamine showed an even stronger protective association, with an adjusted, statistically-significant 67% reduced rate of 30-day readmission for pain compared with the 50% of migraine patients who did not receive an abortive agent prescription after their surgery, said Dr. Platzbecker, a research fellow in the department of anesthesia, critical care, and pain medicine at Beth Israel Deaconess Medical Center in Boston. Only 8% of patients in the study received a triptan or ergotamine, with the vast majority of these patients getting a triptan.

The other types of abortive drugs prescribed perioperatively to migraine patients were NSAIDs or acetaminophen, received by 47% of the patients studied. The adjusted analysis showed that patients who received a prescription for one of these drugs had a statistically significant 35% reduced rate of 30-day readmission for pain. Patients who did not receive a prescription for a migraine abortive drug often got an opioid prescription, which went to 87% of the entire study population. Some patients received perioperative prescriptions for more than one drug. The analysis also showed that periopertive opioid prescriptions had no significant association with the 30-day rate of pain readmissions. In addition, prescription of any pain-reducing medication immediately prior to surgery as prophylaxis, which occurred in 17% of patients, had no significant association with the rate of 30-day postoperative pain readmission.


Despite the lack of clear causal evidence, clinicians should “definitely” be more aggressive in prescribing abortive treatments, especially triptans, to patients with a history of migraine who undergo surgery, Dr. Platzbecker said in an interview. These patients “are likely at risk for migraine [episodes] after surgery,”

Her study used data collected from nearly 25,000 patients with a history of a migraine billing diagnosis who underwent surgery and was a patient in either the Beth Israel or Partners (Massachusetts General Hospital and Brigham and Women’s Hospital) health systems during 2005-2017. Complete data that fulfilled the requirements of the study were available for 21,932 of these patients, of whom 11,011 (50%) received a perioperative prescription for an abortive drug and 10,921 (50%) did not. The prescribing occurred totally at the discretion of each patient’s physicians and surgeons. The researchers defined perioperative prescription as a billing entry for a drug anytime after surgery and within 30 days of hospital discharge or until readmission. The entire group studied averaged about 50 years old, more than 80% were women, and those who received an abortive treatment prescription generally had longer surgeries, more inpatient surgeries, and higher rates of various comorbidities. The adjusted statistical analysis took into account baseline differences like these.

Additional sensitivity analyses showed that perioperative prescriptions for abortive treatments also linked with significant reductions in all 30-day hospital readmissions, and with 30-day pain readmissions in patients who received surgery as inpatients as well as in those who were outpatients, and the association was specific to migraine patients. When Dr. Platzbecker expanded the group of patients she examined to more than 62,000 with any headache diagnosis the association between receiving a prescription for an abortive treatment and reduced 30-day pain readmissions became statistically insignificant.

Dr. Platzbecker and her associates previously reported results from an adjusted analysis showing that patients from the same database with a history of migraine who underwent surgery had an overall 42% increased rate of 30-day readmissions for pain compared with surgery patients who had no migraine history (Cephalagia. 2019 Feb;39[2]:286-95).

Dr. Platzbecker had no commercial disclosures.

[email protected]

On Twitter @mitchelzoler

This article was updated 7/16/19.

PHILADELPHIA – Patients with a history of migraine who underwent any type of surgery and then received a perioperative prescription for a headache abortive agent such as a triptan had 37% fewer readmissions for pain during the 30 days following surgery compared with patients who did not receive a migraine abortive prescription, according to an observational review of nearly 22,000 migraine patients from the Boston area.

Mitchel L. Zoler/MDedge News

While this statistically significant observational association must be viewed with caution, it provides compelling evidence for clinicians to prescribe a migraine abortive agent to migraineurs soon after surgery so that patients have these drugs handy if a migraine strikes, a possibility made likely by the stress and disruption of surgery, Katharina Platzbecker, MD, said at the annual meeting of the American Headache Society.

Postoperative migraine patients who received an abortive prescription specifically for a triptan or ergotamine showed an even stronger protective association, with an adjusted, statistically-significant 67% reduced rate of 30-day readmission for pain compared with the 50% of migraine patients who did not receive an abortive agent prescription after their surgery, said Dr. Platzbecker, a research fellow in the department of anesthesia, critical care, and pain medicine at Beth Israel Deaconess Medical Center in Boston. Only 8% of patients in the study received a triptan or ergotamine, with the vast majority of these patients getting a triptan.

The other types of abortive drugs prescribed perioperatively to migraine patients were NSAIDs or acetaminophen, received by 47% of the patients studied. The adjusted analysis showed that patients who received a prescription for one of these drugs had a statistically significant 35% reduced rate of 30-day readmission for pain. Patients who did not receive a prescription for a migraine abortive drug often got an opioid prescription, which went to 87% of the entire study population. Some patients received perioperative prescriptions for more than one drug. The analysis also showed that periopertive opioid prescriptions had no significant association with the 30-day rate of pain readmissions. In addition, prescription of any pain-reducing medication immediately prior to surgery as prophylaxis, which occurred in 17% of patients, had no significant association with the rate of 30-day postoperative pain readmission.


Despite the lack of clear causal evidence, clinicians should “definitely” be more aggressive in prescribing abortive treatments, especially triptans, to patients with a history of migraine who undergo surgery, Dr. Platzbecker said in an interview. These patients “are likely at risk for migraine [episodes] after surgery,”

Her study used data collected from nearly 25,000 patients with a history of a migraine billing diagnosis who underwent surgery and was a patient in either the Beth Israel or Partners (Massachusetts General Hospital and Brigham and Women’s Hospital) health systems during 2005-2017. Complete data that fulfilled the requirements of the study were available for 21,932 of these patients, of whom 11,011 (50%) received a perioperative prescription for an abortive drug and 10,921 (50%) did not. The prescribing occurred totally at the discretion of each patient’s physicians and surgeons. The researchers defined perioperative prescription as a billing entry for a drug anytime after surgery and within 30 days of hospital discharge or until readmission. The entire group studied averaged about 50 years old, more than 80% were women, and those who received an abortive treatment prescription generally had longer surgeries, more inpatient surgeries, and higher rates of various comorbidities. The adjusted statistical analysis took into account baseline differences like these.

Additional sensitivity analyses showed that perioperative prescriptions for abortive treatments also linked with significant reductions in all 30-day hospital readmissions, and with 30-day pain readmissions in patients who received surgery as inpatients as well as in those who were outpatients, and the association was specific to migraine patients. When Dr. Platzbecker expanded the group of patients she examined to more than 62,000 with any headache diagnosis the association between receiving a prescription for an abortive treatment and reduced 30-day pain readmissions became statistically insignificant.

Dr. Platzbecker and her associates previously reported results from an adjusted analysis showing that patients from the same database with a history of migraine who underwent surgery had an overall 42% increased rate of 30-day readmissions for pain compared with surgery patients who had no migraine history (Cephalagia. 2019 Feb;39[2]:286-95).

Dr. Platzbecker had no commercial disclosures.

[email protected]

On Twitter @mitchelzoler

This article was updated 7/16/19.

PHILADELPHIA – Patients with a history of migraine who underwent any type of surgery and then received a perioperative prescription for a headache abortive agent such as a triptan had 37% fewer readmissions for pain during the 30 days following surgery compared with patients who did not receive a migraine abortive prescription, according to an observational review of nearly 22,000 migraine patients from the Boston area.

Mitchel L. Zoler/MDedge News

While this statistically significant observational association must be viewed with caution, it provides compelling evidence for clinicians to prescribe a migraine abortive agent to migraineurs soon after surgery so that patients have these drugs handy if a migraine strikes, a possibility made likely by the stress and disruption of surgery, Katharina Platzbecker, MD, said at the annual meeting of the American Headache Society.

Postoperative migraine patients who received an abortive prescription specifically for a triptan or ergotamine showed an even stronger protective association, with an adjusted, statistically-significant 67% reduced rate of 30-day readmission for pain compared with the 50% of migraine patients who did not receive an abortive agent prescription after their surgery, said Dr. Platzbecker, a research fellow in the department of anesthesia, critical care, and pain medicine at Beth Israel Deaconess Medical Center in Boston. Only 8% of patients in the study received a triptan or ergotamine, with the vast majority of these patients getting a triptan.

The other types of abortive drugs prescribed perioperatively to migraine patients were NSAIDs or acetaminophen, received by 47% of the patients studied. The adjusted analysis showed that patients who received a prescription for one of these drugs had a statistically significant 35% reduced rate of 30-day readmission for pain. Patients who did not receive a prescription for a migraine abortive drug often got an opioid prescription, which went to 87% of the entire study population. Some patients received perioperative prescriptions for more than one drug. The analysis also showed that periopertive opioid prescriptions had no significant association with the 30-day rate of pain readmissions. In addition, prescription of any pain-reducing medication immediately prior to surgery as prophylaxis, which occurred in 17% of patients, had no significant association with the rate of 30-day postoperative pain readmission.


Despite the lack of clear causal evidence, clinicians should “definitely” be more aggressive in prescribing abortive treatments, especially triptans, to patients with a history of migraine who undergo surgery, Dr. Platzbecker said in an interview. These patients “are likely at risk for migraine [episodes] after surgery,”

Her study used data collected from nearly 25,000 patients with a history of a migraine billing diagnosis who underwent surgery and was a patient in either the Beth Israel or Partners (Massachusetts General Hospital and Brigham and Women’s Hospital) health systems during 2005-2017. Complete data that fulfilled the requirements of the study were available for 21,932 of these patients, of whom 11,011 (50%) received a perioperative prescription for an abortive drug and 10,921 (50%) did not. The prescribing occurred totally at the discretion of each patient’s physicians and surgeons. The researchers defined perioperative prescription as a billing entry for a drug anytime after surgery and within 30 days of hospital discharge or until readmission. The entire group studied averaged about 50 years old, more than 80% were women, and those who received an abortive treatment prescription generally had longer surgeries, more inpatient surgeries, and higher rates of various comorbidities. The adjusted statistical analysis took into account baseline differences like these.

Additional sensitivity analyses showed that perioperative prescriptions for abortive treatments also linked with significant reductions in all 30-day hospital readmissions, and with 30-day pain readmissions in patients who received surgery as inpatients as well as in those who were outpatients, and the association was specific to migraine patients. When Dr. Platzbecker expanded the group of patients she examined to more than 62,000 with any headache diagnosis the association between receiving a prescription for an abortive treatment and reduced 30-day pain readmissions became statistically insignificant.

Dr. Platzbecker and her associates previously reported results from an adjusted analysis showing that patients from the same database with a history of migraine who underwent surgery had an overall 42% increased rate of 30-day readmissions for pain compared with surgery patients who had no migraine history (Cephalagia. 2019 Feb;39[2]:286-95).

Dr. Platzbecker had no commercial disclosures.

[email protected]

On Twitter @mitchelzoler

This article was updated 7/16/19.

PHILADELPHIA – Migraine patients fared as well when managed for a year by telemedicine as when managed by a 12-month series of routine office visits in a single-center, randomized trial with 40 patients, the first reported randomized study of the impact of true telemedicine on mid-term migraine management.

“Telemedicine was viable and produced similar outcomes at 1 year in a highly disabled cohort,” Deborah I. Friedman, MD, said at the annual meeting of the American Headache Society. Many patients expressed high satisfaction with the approach. In addition to resulting in predictably shorter travel times for patients, it also linked with a cut in the consultation length by about a quarter, reported Dr. Friedman, a professor of neurology and chief of the division of headache medicine at UT Southwestern Medical Center in Dallas.

“There is a lot of opportunity for telemedicine, particularly in headache medicine because usually after the first visit we mostly just talk with patients with no further examinations, so it lends itself to telemedicine. It extends your reach.” Dr. Friedman said in a video interview. It is particularly attractive to patients who live a substantial distance from the clinic or find it hard to fit an office visit into their schedule, but some participants said they preferred the direct interaction of an office visit, she noted.

In addition to showing the efficacy of telemedicine in this setting, Dr. Friedman said that she hoped the findings may help pave the way for easier insurance payment for telemedicine consultations with migraineurs.

“One of the main reasons I did this study was to provide evidence to use for compensation for telemedicine visits. It will be good to have evidence in the medical literature that the outcomes are similar and that nothing is lost in patient care with telemedicine,” she said.

The study randomized 40 patients scheduled to see Dr. Friedman for the first time for a migraine consultation and to start treatment. After all patients had their initial office visit and examination, 22 of the patients entered the telemedicine arm and had follow-up consultations after 4-6 weeks, and after 3, 6, 9, and 12 months. The remaining 18 patients were randomized to receive these consultations in the office. Eighteen of the telemedicine patients and 12 of the in-office patients returned for a 12-month assessment. Patients averaged about 40 years old, they had actual or potential travel distances for in-office visits that in some cases exceeded 300 miles one way, and their Migraine Disability Assessment score averaged just above 40.

The telmedicine patients completed 93% of their visits compared with 88% of the in-office patients, a difference that was not statistically different. Migraine Disability Assessment scores improved by an average of 24 points in the telemedicine patients and by an average 19 points among the in-office controls, a difference that was not significant. The two groups also showed similar levels of treatment response for reductions in number of headache days and headache severity improvement. Average session length was 25 minutes with telemedicine and 34 minutes in office, a statistically significant difference that Dr. Friedman attributed to the interest by patients who have traveled long distances to see her to “get their money’s worth” from their visit.


Dr. Friedman highlighted the importance of having the visual aspect of a telemedicine consultation in addition to the conversation. For the trial the audio-visual link was via a standard laptop connection. Some patients assigned to telemedicine voiced regret over not being able to be examined, immediately start a new treatment, or receive drug samples. Dr. Friedman said that she couldn’t think of any migraine patients to whom she wouldn’t offer the option of telemedicine visits following an initial, in-person visit. But her use of telemedicine in routine practice is on hold right now as her institution, UT Southwestern, is still working out its consent and billing system, she said.

The study received partial funding from Merck. Dr. Friedman had no relevant disclosures.

[email protected]

On Twitter @mitchelzoler

SOURCE: Friedman DI. Headache. 2019 June;59[S1]:1-208, LBOR01.

PHILADELPHIA – Migraine patients fared as well when managed for a year by telemedicine as when managed by a 12-month series of routine office visits in a single-center, randomized trial with 40 patients, the first reported randomized study of the impact of true telemedicine on mid-term migraine management.

“Telemedicine was viable and produced similar outcomes at 1 year in a highly disabled cohort,” Deborah I. Friedman, MD, said at the annual meeting of the American Headache Society. Many patients expressed high satisfaction with the approach. In addition to resulting in predictably shorter travel times for patients, it also linked with a cut in the consultation length by about a quarter, reported Dr. Friedman, a professor of neurology and chief of the division of headache medicine at UT Southwestern Medical Center in Dallas.

“There is a lot of opportunity for telemedicine, particularly in headache medicine because usually after the first visit we mostly just talk with patients with no further examinations, so it lends itself to telemedicine. It extends your reach.” Dr. Friedman said in a video interview. It is particularly attractive to patients who live a substantial distance from the clinic or find it hard to fit an office visit into their schedule, but some participants said they preferred the direct interaction of an office visit, she noted.

In addition to showing the efficacy of telemedicine in this setting, Dr. Friedman said that she hoped the findings may help pave the way for easier insurance payment for telemedicine consultations with migraineurs.

“One of the main reasons I did this study was to provide evidence to use for compensation for telemedicine visits. It will be good to have evidence in the medical literature that the outcomes are similar and that nothing is lost in patient care with telemedicine,” she said.

The study randomized 40 patients scheduled to see Dr. Friedman for the first time for a migraine consultation and to start treatment. After all patients had their initial office visit and examination, 22 of the patients entered the telemedicine arm and had follow-up consultations after 4-6 weeks, and after 3, 6, 9, and 12 months. The remaining 18 patients were randomized to receive these consultations in the office. Eighteen of the telemedicine patients and 12 of the in-office patients returned for a 12-month assessment. Patients averaged about 40 years old, they had actual or potential travel distances for in-office visits that in some cases exceeded 300 miles one way, and their Migraine Disability Assessment score averaged just above 40.

The telmedicine patients completed 93% of their visits compared with 88% of the in-office patients, a difference that was not statistically different. Migraine Disability Assessment scores improved by an average of 24 points in the telemedicine patients and by an average 19 points among the in-office controls, a difference that was not significant. The two groups also showed similar levels of treatment response for reductions in number of headache days and headache severity improvement. Average session length was 25 minutes with telemedicine and 34 minutes in office, a statistically significant difference that Dr. Friedman attributed to the interest by patients who have traveled long distances to see her to “get their money’s worth” from their visit.


Dr. Friedman highlighted the importance of having the visual aspect of a telemedicine consultation in addition to the conversation. For the trial the audio-visual link was via a standard laptop connection. Some patients assigned to telemedicine voiced regret over not being able to be examined, immediately start a new treatment, or receive drug samples. Dr. Friedman said that she couldn’t think of any migraine patients to whom she wouldn’t offer the option of telemedicine visits following an initial, in-person visit. But her use of telemedicine in routine practice is on hold right now as her institution, UT Southwestern, is still working out its consent and billing system, she said.

The study received partial funding from Merck. Dr. Friedman had no relevant disclosures.

[email protected]

On Twitter @mitchelzoler

SOURCE: Friedman DI. Headache. 2019 June;59[S1]:1-208, LBOR01.

PHILADELPHIA – Migraine patients fared as well when managed for a year by telemedicine as when managed by a 12-month series of routine office visits in a single-center, randomized trial with 40 patients, the first reported randomized study of the impact of true telemedicine on mid-term migraine management.

“Telemedicine was viable and produced similar outcomes at 1 year in a highly disabled cohort,” Deborah I. Friedman, MD, said at the annual meeting of the American Headache Society. Many patients expressed high satisfaction with the approach. In addition to resulting in predictably shorter travel times for patients, it also linked with a cut in the consultation length by about a quarter, reported Dr. Friedman, a professor of neurology and chief of the division of headache medicine at UT Southwestern Medical Center in Dallas.

“There is a lot of opportunity for telemedicine, particularly in headache medicine because usually after the first visit we mostly just talk with patients with no further examinations, so it lends itself to telemedicine. It extends your reach.” Dr. Friedman said in a video interview. It is particularly attractive to patients who live a substantial distance from the clinic or find it hard to fit an office visit into their schedule, but some participants said they preferred the direct interaction of an office visit, she noted.

In addition to showing the efficacy of telemedicine in this setting, Dr. Friedman said that she hoped the findings may help pave the way for easier insurance payment for telemedicine consultations with migraineurs.

“One of the main reasons I did this study was to provide evidence to use for compensation for telemedicine visits. It will be good to have evidence in the medical literature that the outcomes are similar and that nothing is lost in patient care with telemedicine,” she said.

The study randomized 40 patients scheduled to see Dr. Friedman for the first time for a migraine consultation and to start treatment. After all patients had their initial office visit and examination, 22 of the patients entered the telemedicine arm and had follow-up consultations after 4-6 weeks, and after 3, 6, 9, and 12 months. The remaining 18 patients were randomized to receive these consultations in the office. Eighteen of the telemedicine patients and 12 of the in-office patients returned for a 12-month assessment. Patients averaged about 40 years old, they had actual or potential travel distances for in-office visits that in some cases exceeded 300 miles one way, and their Migraine Disability Assessment score averaged just above 40.

The telmedicine patients completed 93% of their visits compared with 88% of the in-office patients, a difference that was not statistically different. Migraine Disability Assessment scores improved by an average of 24 points in the telemedicine patients and by an average 19 points among the in-office controls, a difference that was not significant. The two groups also showed similar levels of treatment response for reductions in number of headache days and headache severity improvement. Average session length was 25 minutes with telemedicine and 34 minutes in office, a statistically significant difference that Dr. Friedman attributed to the interest by patients who have traveled long distances to see her to “get their money’s worth” from their visit.


Dr. Friedman highlighted the importance of having the visual aspect of a telemedicine consultation in addition to the conversation. For the trial the audio-visual link was via a standard laptop connection. Some patients assigned to telemedicine voiced regret over not being able to be examined, immediately start a new treatment, or receive drug samples. Dr. Friedman said that she couldn’t think of any migraine patients to whom she wouldn’t offer the option of telemedicine visits following an initial, in-person visit. But her use of telemedicine in routine practice is on hold right now as her institution, UT Southwestern, is still working out its consent and billing system, she said.

The study received partial funding from Merck. Dr. Friedman had no relevant disclosures.

[email protected]

On Twitter @mitchelzoler

SOURCE: Friedman DI. Headache. 2019 June;59[S1]:1-208, LBOR01.

Among patients with osteoporosis who have diminished long-term response to bisphosphonate therapy, the addition of eldecalcitol may reduce bone turnover markers and increase bone mineral density, according a study in Osteoporosis and Sarcopenia.

Bisphosphonates may increase bone mineral density, but their efficacy “can diminish over longer treatment periods, and bone mineral density plateaus and even decreases have been encountered regardless of the bisphosphonate usage,” said lead study author Mikio Kamimura, MD, PhD, a researcher at the Kamimura Orthopedic Clinic’s Center of Osteoporosis and Spinal Disorders in Matsumoto, Japan, and colleagues.

Eldecalcitol is an active vitamin D₃ derivative approved in Japan for the treatment of osteoporosis. A prior study suggested that bisphosphonate therapy combined with eldecalcitol is more effective than bisphosphonate therapy combined with alfacalcidol, another vitamin D analog, for the treatment of osteoporosis (Tohoku J Exp Med. 2015 Dec;237[4]:339-43.). Investigators had not studied the additive effects of eldecalcitol in patients who are poor responders to long-term bisphosphonate therapy, however.

To examine this question, researchers in Japan conducted a prospective cohort study. Dr. Kamimura and colleagues analyzed data from 42 postmenopausal Japanese women with primary osteoporosis who were poor responders to bisphosphonates – that is, their low lumbar bone mineral density or bilateral total hip bone mineral density did not apparently increase with chronic bisphosphonate treatment over 2 years. The patients had an average age of about 73 years. They received bisphosphonate therapy with alendronate, risedronate, or minodronate. During the study, participants added daily oral eldecalcitol 0.75 mcg/day after breakfast.

The researchers measured markers of bone formation and bone resorption before bisphosphonate therapy, before adding eldecalcitol, and 4 months after starting eldecalcitol. They also assessed measures of bone mineral density.

Serum bone alkaline phosphatase, a bone formation marker, and urinary N-terminal telopeptide of type I collagen, a bone resorption marker, significantly decreased with bisphosphonate therapy. Added eldecalcitol decreased both bone turnover markers further.

Average low lumbar bone mineral density increase rate was 0.2% from 2 to 1 years before eldecalcitol administration, −0.7% during the year before eldecalcitol administration, and 2.9% during 1 year of eldecalcitol therapy. Similarly, mean increase rates of bilateral total hip bone mineral density were 0.2%, −0.7%, and 1.2%, respectively. Mean femoral neck bone mineral density increase rate was 1.1% after eldecalcitol administration, whereas the cohort had no gains with bisphosphonate therapy alone.

In osteoporotic patients exhibiting a poor response to long-term bisphosphonate therapy, the addition of eldecalcitol may represent “a good treatment option,” the authors concluded.

The small sample size, short follow-up period, and lack of evaluation of fracture prevention are limitations of the study, and further studies are needed to confirm these results, the researchers acknowledged.

The authors reported no relevant conflicts of interest.
[email protected]

SOURCE: Kamimura M et al. Osteoporos Sarcopenia. 2019 Jun 28. doi: 10.1016/j.afos.2019.06.001.

Among patients with osteoporosis who have diminished long-term response to bisphosphonate therapy, the addition of eldecalcitol may reduce bone turnover markers and increase bone mineral density, according a study in Osteoporosis and Sarcopenia.

Bisphosphonates may increase bone mineral density, but their efficacy “can diminish over longer treatment periods, and bone mineral density plateaus and even decreases have been encountered regardless of the bisphosphonate usage,” said lead study author Mikio Kamimura, MD, PhD, a researcher at the Kamimura Orthopedic Clinic’s Center of Osteoporosis and Spinal Disorders in Matsumoto, Japan, and colleagues.

Eldecalcitol is an active vitamin D₃ derivative approved in Japan for the treatment of osteoporosis. A prior study suggested that bisphosphonate therapy combined with eldecalcitol is more effective than bisphosphonate therapy combined with alfacalcidol, another vitamin D analog, for the treatment of osteoporosis (Tohoku J Exp Med. 2015 Dec;237[4]:339-43.). Investigators had not studied the additive effects of eldecalcitol in patients who are poor responders to long-term bisphosphonate therapy, however.

To examine this question, researchers in Japan conducted a prospective cohort study. Dr. Kamimura and colleagues analyzed data from 42 postmenopausal Japanese women with primary osteoporosis who were poor responders to bisphosphonates – that is, their low lumbar bone mineral density or bilateral total hip bone mineral density did not apparently increase with chronic bisphosphonate treatment over 2 years. The patients had an average age of about 73 years. They received bisphosphonate therapy with alendronate, risedronate, or minodronate. During the study, participants added daily oral eldecalcitol 0.75 mcg/day after breakfast.

The researchers measured markers of bone formation and bone resorption before bisphosphonate therapy, before adding eldecalcitol, and 4 months after starting eldecalcitol. They also assessed measures of bone mineral density.

Serum bone alkaline phosphatase, a bone formation marker, and urinary N-terminal telopeptide of type I collagen, a bone resorption marker, significantly decreased with bisphosphonate therapy. Added eldecalcitol decreased both bone turnover markers further.

Average low lumbar bone mineral density increase rate was 0.2% from 2 to 1 years before eldecalcitol administration, −0.7% during the year before eldecalcitol administration, and 2.9% during 1 year of eldecalcitol therapy. Similarly, mean increase rates of bilateral total hip bone mineral density were 0.2%, −0.7%, and 1.2%, respectively. Mean femoral neck bone mineral density increase rate was 1.1% after eldecalcitol administration, whereas the cohort had no gains with bisphosphonate therapy alone.

In osteoporotic patients exhibiting a poor response to long-term bisphosphonate therapy, the addition of eldecalcitol may represent “a good treatment option,” the authors concluded.

The small sample size, short follow-up period, and lack of evaluation of fracture prevention are limitations of the study, and further studies are needed to confirm these results, the researchers acknowledged.

The authors reported no relevant conflicts of interest.
[email protected]

SOURCE: Kamimura M et al. Osteoporos Sarcopenia. 2019 Jun 28. doi: 10.1016/j.afos.2019.06.001.

Among patients with osteoporosis who have diminished long-term response to bisphosphonate therapy, the addition of eldecalcitol may reduce bone turnover markers and increase bone mineral density, according a study in Osteoporosis and Sarcopenia.

Bisphosphonates may increase bone mineral density, but their efficacy “can diminish over longer treatment periods, and bone mineral density plateaus and even decreases have been encountered regardless of the bisphosphonate usage,” said lead study author Mikio Kamimura, MD, PhD, a researcher at the Kamimura Orthopedic Clinic’s Center of Osteoporosis and Spinal Disorders in Matsumoto, Japan, and colleagues.

Eldecalcitol is an active vitamin D₃ derivative approved in Japan for the treatment of osteoporosis. A prior study suggested that bisphosphonate therapy combined with eldecalcitol is more effective than bisphosphonate therapy combined with alfacalcidol, another vitamin D analog, for the treatment of osteoporosis (Tohoku J Exp Med. 2015 Dec;237[4]:339-43.). Investigators had not studied the additive effects of eldecalcitol in patients who are poor responders to long-term bisphosphonate therapy, however.

To examine this question, researchers in Japan conducted a prospective cohort study. Dr. Kamimura and colleagues analyzed data from 42 postmenopausal Japanese women with primary osteoporosis who were poor responders to bisphosphonates – that is, their low lumbar bone mineral density or bilateral total hip bone mineral density did not apparently increase with chronic bisphosphonate treatment over 2 years. The patients had an average age of about 73 years. They received bisphosphonate therapy with alendronate, risedronate, or minodronate. During the study, participants added daily oral eldecalcitol 0.75 mcg/day after breakfast.

The researchers measured markers of bone formation and bone resorption before bisphosphonate therapy, before adding eldecalcitol, and 4 months after starting eldecalcitol. They also assessed measures of bone mineral density.

Serum bone alkaline phosphatase, a bone formation marker, and urinary N-terminal telopeptide of type I collagen, a bone resorption marker, significantly decreased with bisphosphonate therapy. Added eldecalcitol decreased both bone turnover markers further.

Average low lumbar bone mineral density increase rate was 0.2% from 2 to 1 years before eldecalcitol administration, −0.7% during the year before eldecalcitol administration, and 2.9% during 1 year of eldecalcitol therapy. Similarly, mean increase rates of bilateral total hip bone mineral density were 0.2%, −0.7%, and 1.2%, respectively. Mean femoral neck bone mineral density increase rate was 1.1% after eldecalcitol administration, whereas the cohort had no gains with bisphosphonate therapy alone.

In osteoporotic patients exhibiting a poor response to long-term bisphosphonate therapy, the addition of eldecalcitol may represent “a good treatment option,” the authors concluded.

The small sample size, short follow-up period, and lack of evaluation of fracture prevention are limitations of the study, and further studies are needed to confirm these results, the researchers acknowledged.

The authors reported no relevant conflicts of interest.
[email protected]

SOURCE: Kamimura M et al. Osteoporos Sarcopenia. 2019 Jun 28. doi: 10.1016/j.afos.2019.06.001.

PHILADELPHIA – The headache field is not free of the gender bias that affects medicine in general, said Elizabeth W. Loder, MD, chief of the Division of Headache and Pain at Brigham and Women’s Hospital in Boston, at the annual meeting of the American Headache Society. Women accrue credentials and are accorded respect as headache experts more slowly than men, she said. They are underrepresented among the speakers at headache conferences and are less likely than men to be invited to write editorials for peer-reviewed publications. Furthermore, a significant proportion of female headache specialists experiences sexual harassment in their professional environments.

Bias also affects interactions between patients and headache specialists, said Dr. Loder. Regardless of their gender, patients expect female care providers to be sympathetic and understanding. If they perceive that a female physician does not sufficiently display these attributes, they often write critical reviews of them on the Internet. In contrast, male physicians are not expected to be particularly caring, and patients praise them highly when they are.

Recognition of these biases is increasing, however. Representation of women in professional societies and on conference programs will improve, and emerging codes of conduct will reduce sexual harassment, said Dr. Loder. Headache specialists can take various steps, such as offering recognition and encouragement, to make the field more welcoming to women and to other disadvantaged groups.

[email protected]

PHILADELPHIA – The headache field is not free of the gender bias that affects medicine in general, said Elizabeth W. Loder, MD, chief of the Division of Headache and Pain at Brigham and Women’s Hospital in Boston, at the annual meeting of the American Headache Society. Women accrue credentials and are accorded respect as headache experts more slowly than men, she said. They are underrepresented among the speakers at headache conferences and are less likely than men to be invited to write editorials for peer-reviewed publications. Furthermore, a significant proportion of female headache specialists experiences sexual harassment in their professional environments.

Bias also affects interactions between patients and headache specialists, said Dr. Loder. Regardless of their gender, patients expect female care providers to be sympathetic and understanding. If they perceive that a female physician does not sufficiently display these attributes, they often write critical reviews of them on the Internet. In contrast, male physicians are not expected to be particularly caring, and patients praise them highly when they are.

Recognition of these biases is increasing, however. Representation of women in professional societies and on conference programs will improve, and emerging codes of conduct will reduce sexual harassment, said Dr. Loder. Headache specialists can take various steps, such as offering recognition and encouragement, to make the field more welcoming to women and to other disadvantaged groups.

[email protected]

PHILADELPHIA – The headache field is not free of the gender bias that affects medicine in general, said Elizabeth W. Loder, MD, chief of the Division of Headache and Pain at Brigham and Women’s Hospital in Boston, at the annual meeting of the American Headache Society. Women accrue credentials and are accorded respect as headache experts more slowly than men, she said. They are underrepresented among the speakers at headache conferences and are less likely than men to be invited to write editorials for peer-reviewed publications. Furthermore, a significant proportion of female headache specialists experiences sexual harassment in their professional environments.

Bias also affects interactions between patients and headache specialists, said Dr. Loder. Regardless of their gender, patients expect female care providers to be sympathetic and understanding. If they perceive that a female physician does not sufficiently display these attributes, they often write critical reviews of them on the Internet. In contrast, male physicians are not expected to be particularly caring, and patients praise them highly when they are.

Recognition of these biases is increasing, however. Representation of women in professional societies and on conference programs will improve, and emerging codes of conduct will reduce sexual harassment, said Dr. Loder. Headache specialists can take various steps, such as offering recognition and encouragement, to make the field more welcoming to women and to other disadvantaged groups.

[email protected]