Diabetes Hub

ORLANDO – Whether to start a patient with newly diagnosed type 2 diabetes mellitus on combination therapy or monotherapy should be based on experimentation and observation rather than expert opinion, according to Dr. Alan Garber, president of the American College of Endocrinology and professor of medicine, biochemistry, and molecular and cellular biology at Baylor College of Medicine in Houston.

Monotherapy for type 2 diabetes with stepwise addition of other antihyperglycemic agents has long been the accepted way to initiate therapy in this population. Beginning in the 1990s, investigators began to compare the efficacy of monotherapy with combination therapy, first with metformin and glyburide alone or together, and then testing metformin in combination with glipizide, rosiglitazone, and sitagliptin, he said.

For metformin and glyburide, each agent alone lowered glycated hemoglobin (HbA_1c), compared with placebo, but adding one to the other enhanced lowering. Combining the two drugs had the greatest benefit for higher HbA_1c entry levels (e.g., HbA_1c strata of 9%-9.9% or 10% or greater vs. less than 8%). At the highest-entry HbA_1c levels, half doses of each of metformin and glyburide (250 mg/1.25 mg, respectively) were more efficacious than full doses of each (500 mg/2.5 mg). “This is called drug sparing,” he said.

In a trial of metformin and rosiglitazone, the combination was superior to either alone, producing significantly greater mean reductions in HbA_1c and in fasting plasma glucose (FPG) at 32 weeks from their respective baselines, again, with greater reductions for higher-entry HbA_1c levels. The combination was also better than either drug alone in the speed of reducing HbA_1c or FPG, and in the final attained levels.

The combination of metformin and a sulfonylurea presents a risk of hypoglycemia, but Dr. Garber said the results are “much cleaner” using combinations of metformin with agents such as a thiazolidinedione, a dipeptidyl peptidase-4 inhibitor, or a sodium/glucose cotransporter-2 inhibitor.

Also noteworthy are findings from the EDICT (Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes) trial using insulin-sensitizing and insulin-secreting agents metformin/pioglitazone/exenatide in combination vs. escalating doses of metformin with sequential addition of a sulfonylurea and glargine insulin to treat patients with newly diagnosed type 2 diabetes. Over 2 years, the subjects receiving combination therapy had lower HbA_1c, a mean weight loss, compared with weight gain, in the sequential therapy group, and a 7.5-fold lower rate of hypoglycemia, compared with the sequential treatment group (Diabetes Obes Metab. 2015;17:268-75).

Although the agents used in the two treatment strategies were not strictly equivalent, “it’s clear that testing multiple therapeutic mechanisms tends to produce better outcomes than fewer therapeutic mechanisms,” Dr. Garber said. The conclusions are fairly straightforward. “Look for evidence to support what strategies you want to use for your patients’ care.”

Using the Kaiser Permanente database, investigators found that the mean time of having an HbA_1c above 8% was 3 years before a second agent was added, and the mean HbA_1c was 9%. Many people have ascribed this sort of delay to a problem with the physician. But Dr. Garber said it is more related to patients, who often resist prescriptions for more drugs. So starting with two drugs may produce better efficacy faster as well as overcome the psychological issues of trying to add another one later (Am J Manag Care. 2003;9:213-7).

Session moderator Dr. Daniel Einhorn, medical director of the Scripps Whittier Diabetes Institute in La Jolla, California, raised the possibility of “subtraction therapy, where you start with three agents no matter what, and then if things go well, you subtract. And so you reverse the situation that Alan discussed.” In the patient’s view, “you have a celebration that night instead of a wake,” he said.

Dr. Garber has received honoraria or consulting fees as a member of the advisory boards of Novo Nordisk, Janssen, and Merck. Dr. Einhorn is on the scientific advisory boards of Eli Lilly, Novo Nordisk, Janssen, Boehringer Ingelheim, Sanofi, and Adocia, is a consultant for Halozyme, Glysens, Freedom-Meditech, and Epitracker, and has research funding from Lilly, Novo, Janssen, AstraZeneca, Mannkind, Freedom-Meditech, Merck, Sanofi, and Boehringer Ingelheim.

ORLANDO – Whether to start a patient with newly diagnosed type 2 diabetes mellitus on combination therapy or monotherapy should be based on experimentation and observation rather than expert opinion, according to Dr. Alan Garber, president of the American College of Endocrinology and professor of medicine, biochemistry, and molecular and cellular biology at Baylor College of Medicine in Houston.

Monotherapy for type 2 diabetes with stepwise addition of other antihyperglycemic agents has long been the accepted way to initiate therapy in this population. Beginning in the 1990s, investigators began to compare the efficacy of monotherapy with combination therapy, first with metformin and glyburide alone or together, and then testing metformin in combination with glipizide, rosiglitazone, and sitagliptin, he said.

For metformin and glyburide, each agent alone lowered glycated hemoglobin (HbA_1c), compared with placebo, but adding one to the other enhanced lowering. Combining the two drugs had the greatest benefit for higher HbA_1c entry levels (e.g., HbA_1c strata of 9%-9.9% or 10% or greater vs. less than 8%). At the highest-entry HbA_1c levels, half doses of each of metformin and glyburide (250 mg/1.25 mg, respectively) were more efficacious than full doses of each (500 mg/2.5 mg). “This is called drug sparing,” he said.

In a trial of metformin and rosiglitazone, the combination was superior to either alone, producing significantly greater mean reductions in HbA_1c and in fasting plasma glucose (FPG) at 32 weeks from their respective baselines, again, with greater reductions for higher-entry HbA_1c levels. The combination was also better than either drug alone in the speed of reducing HbA_1c or FPG, and in the final attained levels.

The combination of metformin and a sulfonylurea presents a risk of hypoglycemia, but Dr. Garber said the results are “much cleaner” using combinations of metformin with agents such as a thiazolidinedione, a dipeptidyl peptidase-4 inhibitor, or a sodium/glucose cotransporter-2 inhibitor.

Also noteworthy are findings from the EDICT (Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes) trial using insulin-sensitizing and insulin-secreting agents metformin/pioglitazone/exenatide in combination vs. escalating doses of metformin with sequential addition of a sulfonylurea and glargine insulin to treat patients with newly diagnosed type 2 diabetes. Over 2 years, the subjects receiving combination therapy had lower HbA_1c, a mean weight loss, compared with weight gain, in the sequential therapy group, and a 7.5-fold lower rate of hypoglycemia, compared with the sequential treatment group (Diabetes Obes Metab. 2015;17:268-75).

Although the agents used in the two treatment strategies were not strictly equivalent, “it’s clear that testing multiple therapeutic mechanisms tends to produce better outcomes than fewer therapeutic mechanisms,” Dr. Garber said. The conclusions are fairly straightforward. “Look for evidence to support what strategies you want to use for your patients’ care.”

Using the Kaiser Permanente database, investigators found that the mean time of having an HbA_1c above 8% was 3 years before a second agent was added, and the mean HbA_1c was 9%. Many people have ascribed this sort of delay to a problem with the physician. But Dr. Garber said it is more related to patients, who often resist prescriptions for more drugs. So starting with two drugs may produce better efficacy faster as well as overcome the psychological issues of trying to add another one later (Am J Manag Care. 2003;9:213-7).

Session moderator Dr. Daniel Einhorn, medical director of the Scripps Whittier Diabetes Institute in La Jolla, California, raised the possibility of “subtraction therapy, where you start with three agents no matter what, and then if things go well, you subtract. And so you reverse the situation that Alan discussed.” In the patient’s view, “you have a celebration that night instead of a wake,” he said.

Dr. Garber has received honoraria or consulting fees as a member of the advisory boards of Novo Nordisk, Janssen, and Merck. Dr. Einhorn is on the scientific advisory boards of Eli Lilly, Novo Nordisk, Janssen, Boehringer Ingelheim, Sanofi, and Adocia, is a consultant for Halozyme, Glysens, Freedom-Meditech, and Epitracker, and has research funding from Lilly, Novo, Janssen, AstraZeneca, Mannkind, Freedom-Meditech, Merck, Sanofi, and Boehringer Ingelheim.

ORLANDO – Whether to start a patient with newly diagnosed type 2 diabetes mellitus on combination therapy or monotherapy should be based on experimentation and observation rather than expert opinion, according to Dr. Alan Garber, president of the American College of Endocrinology and professor of medicine, biochemistry, and molecular and cellular biology at Baylor College of Medicine in Houston.

Monotherapy for type 2 diabetes with stepwise addition of other antihyperglycemic agents has long been the accepted way to initiate therapy in this population. Beginning in the 1990s, investigators began to compare the efficacy of monotherapy with combination therapy, first with metformin and glyburide alone or together, and then testing metformin in combination with glipizide, rosiglitazone, and sitagliptin, he said.

For metformin and glyburide, each agent alone lowered glycated hemoglobin (HbA_1c), compared with placebo, but adding one to the other enhanced lowering. Combining the two drugs had the greatest benefit for higher HbA_1c entry levels (e.g., HbA_1c strata of 9%-9.9% or 10% or greater vs. less than 8%). At the highest-entry HbA_1c levels, half doses of each of metformin and glyburide (250 mg/1.25 mg, respectively) were more efficacious than full doses of each (500 mg/2.5 mg). “This is called drug sparing,” he said.

In a trial of metformin and rosiglitazone, the combination was superior to either alone, producing significantly greater mean reductions in HbA_1c and in fasting plasma glucose (FPG) at 32 weeks from their respective baselines, again, with greater reductions for higher-entry HbA_1c levels. The combination was also better than either drug alone in the speed of reducing HbA_1c or FPG, and in the final attained levels.

The combination of metformin and a sulfonylurea presents a risk of hypoglycemia, but Dr. Garber said the results are “much cleaner” using combinations of metformin with agents such as a thiazolidinedione, a dipeptidyl peptidase-4 inhibitor, or a sodium/glucose cotransporter-2 inhibitor.

Also noteworthy are findings from the EDICT (Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes) trial using insulin-sensitizing and insulin-secreting agents metformin/pioglitazone/exenatide in combination vs. escalating doses of metformin with sequential addition of a sulfonylurea and glargine insulin to treat patients with newly diagnosed type 2 diabetes. Over 2 years, the subjects receiving combination therapy had lower HbA_1c, a mean weight loss, compared with weight gain, in the sequential therapy group, and a 7.5-fold lower rate of hypoglycemia, compared with the sequential treatment group (Diabetes Obes Metab. 2015;17:268-75).

Although the agents used in the two treatment strategies were not strictly equivalent, “it’s clear that testing multiple therapeutic mechanisms tends to produce better outcomes than fewer therapeutic mechanisms,” Dr. Garber said. The conclusions are fairly straightforward. “Look for evidence to support what strategies you want to use for your patients’ care.”

Using the Kaiser Permanente database, investigators found that the mean time of having an HbA_1c above 8% was 3 years before a second agent was added, and the mean HbA_1c was 9%. Many people have ascribed this sort of delay to a problem with the physician. But Dr. Garber said it is more related to patients, who often resist prescriptions for more drugs. So starting with two drugs may produce better efficacy faster as well as overcome the psychological issues of trying to add another one later (Am J Manag Care. 2003;9:213-7).

Session moderator Dr. Daniel Einhorn, medical director of the Scripps Whittier Diabetes Institute in La Jolla, California, raised the possibility of “subtraction therapy, where you start with three agents no matter what, and then if things go well, you subtract. And so you reverse the situation that Alan discussed.” In the patient’s view, “you have a celebration that night instead of a wake,” he said.

Dr. Garber has received honoraria or consulting fees as a member of the advisory boards of Novo Nordisk, Janssen, and Merck. Dr. Einhorn is on the scientific advisory boards of Eli Lilly, Novo Nordisk, Janssen, Boehringer Ingelheim, Sanofi, and Adocia, is a consultant for Halozyme, Glysens, Freedom-Meditech, and Epitracker, and has research funding from Lilly, Novo, Janssen, AstraZeneca, Mannkind, Freedom-Meditech, Merck, Sanofi, and Boehringer Ingelheim.

Among patients with type 2 diabetes, those with foot ulcers show cognitive impairment across all domains when compared with those without, according to a report published in Diabetes Care.

In what they described as one of the first studies to examine cognitive function in people with diabetic foot ulcers, researchers found that these patients “remember less, have decreased ability to concentrate, and more difficulty with learning, less inhibition, slower cognitive and psychomotor responses, and less verbal fluency” than patients with diabetes that does not include foot involvement.

©Balkonsky/ThinkStockPhotos

Although this study had a cross-sectional design that precluded drawing conclusions about causality, an analysis that estimated the participants’ premorbid and postmorbid cognitive abilities suggested that people with diabetic foot ulcers had experienced a recent significant cognitive decline, while those without foot ulcers had not, said Rachel Natovich, Ph.D., of the department of public health, Ben-Gurion University of the Negev, Be’er Sheva (Israel) and the Endocrinology Institute, Sheba Medical Center, Ramat Gan (Israel) and her associates. These findings indicate that patients with diabetic foot ulcers – the very patients who face the greatest self-treatment challenges – are the ones who have the weakest cognitive resources to do so, they noted.

The investigators examined this issue after noting that recent consensus guidelines require patients with diabetic foot ulcers to take on even more self-management than is already required for the diabetes. This demands “applying complex cognitive abilities in learning, understanding, and remembering new information; planning and initiating self-care practices; adopting behavioral changes that involve psychomotor abilities; and maintaining these behaviors while controlling and repressing impulses.” So Dr. Natovich and her associates assessed whether the cognitive profile of patients who have diabetic foot problems differs from that of patients who don’t, using a case-control study design.

The 194 study participants were aged 45-75 years. The 99 subjects who had at least one diabetic foot ulcer (cases) were matched for age and duration of diabetes with 95 subjects who did not (controls). All underwent a comprehensive battery of neuropsychological tests assessing general intelligence, short- and long-term memory, attention and concentration, psychomotor efficiency, reaction time, executive function, nonverbal IQ, visual-motor speed, coordination, capacity for learning, verbal production, semantic memory, and language. All were also assessed for depression via the Patient Health Questionnaire.

After scores were standardized according to the expected performance by age and education level, patients with diabetic foot ulcers showed significantly lower scores in all the domains tested, compared with the patients without foot ulcers. This difference persisted after the data were adjusted to account for possible confounding factors such as smoking status, hemoglobin A_1c level, presence or absence of depressive symptoms, and presence or absence of macrovascular disease (Diab Care. 2016 May. doi:10.2337/dc15-2838).

The estimated premorbid cognitive function was similar between the two study groups, but current cognitive function declined significantly in the patients with foot ulcers while remaining relatively constant in the patients without foot ulcers. Prospective studies are needed to explore the timing of cognitive decline and the possibility of causation, Dr. Natovich and her associates said.

The study results “highlight the importance of focusing on cognitive functioning, a less-studied area in diabetic foot research,” they added.

“We feel that it is important to screen the cognitive status of these patients regularly and to take cognitive abilities into consideration in treatment-planning recommendations and follow-up.”

Among patients with type 2 diabetes, those with foot ulcers show cognitive impairment across all domains when compared with those without, according to a report published in Diabetes Care.

In what they described as one of the first studies to examine cognitive function in people with diabetic foot ulcers, researchers found that these patients “remember less, have decreased ability to concentrate, and more difficulty with learning, less inhibition, slower cognitive and psychomotor responses, and less verbal fluency” than patients with diabetes that does not include foot involvement.

©Balkonsky/ThinkStockPhotos

Although this study had a cross-sectional design that precluded drawing conclusions about causality, an analysis that estimated the participants’ premorbid and postmorbid cognitive abilities suggested that people with diabetic foot ulcers had experienced a recent significant cognitive decline, while those without foot ulcers had not, said Rachel Natovich, Ph.D., of the department of public health, Ben-Gurion University of the Negev, Be’er Sheva (Israel) and the Endocrinology Institute, Sheba Medical Center, Ramat Gan (Israel) and her associates. These findings indicate that patients with diabetic foot ulcers – the very patients who face the greatest self-treatment challenges – are the ones who have the weakest cognitive resources to do so, they noted.

The investigators examined this issue after noting that recent consensus guidelines require patients with diabetic foot ulcers to take on even more self-management than is already required for the diabetes. This demands “applying complex cognitive abilities in learning, understanding, and remembering new information; planning and initiating self-care practices; adopting behavioral changes that involve psychomotor abilities; and maintaining these behaviors while controlling and repressing impulses.” So Dr. Natovich and her associates assessed whether the cognitive profile of patients who have diabetic foot problems differs from that of patients who don’t, using a case-control study design.

The 194 study participants were aged 45-75 years. The 99 subjects who had at least one diabetic foot ulcer (cases) were matched for age and duration of diabetes with 95 subjects who did not (controls). All underwent a comprehensive battery of neuropsychological tests assessing general intelligence, short- and long-term memory, attention and concentration, psychomotor efficiency, reaction time, executive function, nonverbal IQ, visual-motor speed, coordination, capacity for learning, verbal production, semantic memory, and language. All were also assessed for depression via the Patient Health Questionnaire.

After scores were standardized according to the expected performance by age and education level, patients with diabetic foot ulcers showed significantly lower scores in all the domains tested, compared with the patients without foot ulcers. This difference persisted after the data were adjusted to account for possible confounding factors such as smoking status, hemoglobin A_1c level, presence or absence of depressive symptoms, and presence or absence of macrovascular disease (Diab Care. 2016 May. doi:10.2337/dc15-2838).

The estimated premorbid cognitive function was similar between the two study groups, but current cognitive function declined significantly in the patients with foot ulcers while remaining relatively constant in the patients without foot ulcers. Prospective studies are needed to explore the timing of cognitive decline and the possibility of causation, Dr. Natovich and her associates said.

The study results “highlight the importance of focusing on cognitive functioning, a less-studied area in diabetic foot research,” they added.

“We feel that it is important to screen the cognitive status of these patients regularly and to take cognitive abilities into consideration in treatment-planning recommendations and follow-up.”

Among patients with type 2 diabetes, those with foot ulcers show cognitive impairment across all domains when compared with those without, according to a report published in Diabetes Care.

In what they described as one of the first studies to examine cognitive function in people with diabetic foot ulcers, researchers found that these patients “remember less, have decreased ability to concentrate, and more difficulty with learning, less inhibition, slower cognitive and psychomotor responses, and less verbal fluency” than patients with diabetes that does not include foot involvement.

©Balkonsky/ThinkStockPhotos

Although this study had a cross-sectional design that precluded drawing conclusions about causality, an analysis that estimated the participants’ premorbid and postmorbid cognitive abilities suggested that people with diabetic foot ulcers had experienced a recent significant cognitive decline, while those without foot ulcers had not, said Rachel Natovich, Ph.D., of the department of public health, Ben-Gurion University of the Negev, Be’er Sheva (Israel) and the Endocrinology Institute, Sheba Medical Center, Ramat Gan (Israel) and her associates. These findings indicate that patients with diabetic foot ulcers – the very patients who face the greatest self-treatment challenges – are the ones who have the weakest cognitive resources to do so, they noted.

The investigators examined this issue after noting that recent consensus guidelines require patients with diabetic foot ulcers to take on even more self-management than is already required for the diabetes. This demands “applying complex cognitive abilities in learning, understanding, and remembering new information; planning and initiating self-care practices; adopting behavioral changes that involve psychomotor abilities; and maintaining these behaviors while controlling and repressing impulses.” So Dr. Natovich and her associates assessed whether the cognitive profile of patients who have diabetic foot problems differs from that of patients who don’t, using a case-control study design.

The 194 study participants were aged 45-75 years. The 99 subjects who had at least one diabetic foot ulcer (cases) were matched for age and duration of diabetes with 95 subjects who did not (controls). All underwent a comprehensive battery of neuropsychological tests assessing general intelligence, short- and long-term memory, attention and concentration, psychomotor efficiency, reaction time, executive function, nonverbal IQ, visual-motor speed, coordination, capacity for learning, verbal production, semantic memory, and language. All were also assessed for depression via the Patient Health Questionnaire.

After scores were standardized according to the expected performance by age and education level, patients with diabetic foot ulcers showed significantly lower scores in all the domains tested, compared with the patients without foot ulcers. This difference persisted after the data were adjusted to account for possible confounding factors such as smoking status, hemoglobin A_1c level, presence or absence of depressive symptoms, and presence or absence of macrovascular disease (Diab Care. 2016 May. doi:10.2337/dc15-2838).

The estimated premorbid cognitive function was similar between the two study groups, but current cognitive function declined significantly in the patients with foot ulcers while remaining relatively constant in the patients without foot ulcers. Prospective studies are needed to explore the timing of cognitive decline and the possibility of causation, Dr. Natovich and her associates said.

The study results “highlight the importance of focusing on cognitive functioning, a less-studied area in diabetic foot research,” they added.

“We feel that it is important to screen the cognitive status of these patients regularly and to take cognitive abilities into consideration in treatment-planning recommendations and follow-up.”

Interim safety results from an ongoing clinical trial found an increase in leg and foot amputations, mostly affecting the toes, in patients treated with the diabetes medicine canagliflozin, according to an FDA Drug Safety Communication on May 18, 2016.

The agency currently is investigating the safety issue but has yet to determine if taking canagliflozin is associated with an increased risk of leg and foot amputations. A sodium-glucose cotransporter 2 inhibitor, canagliflozin is marketed as Invokana and Invokamet by Janssen Pharmaceuticals, and was approved by the FDA in March 2013.

“Patients should not stop or change their diabetes medicines without first talking to their health care professional,” the communication states. “Doing so can lead to uncontrolled blood sugar levels that can be harmful. Over time, this can cause serious problems, including blindness, nerve and kidney damage, and heart disease. Patients taking canagliflozin should notify their health care professionals right away if they notice any new pain or tenderness, sores or ulcers, or infections in their legs or feet.”

The agency advises health care professionals to follow the recommendations in the canagliflozin drug labels and to monitor patients for the signs and symptoms described above.

Upon its approval, the FDA required five postmarketing studies for canagliflozin: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the Pediatric Research Equity Act (PREA), including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study. In late 2015, investigators determined that the risk of bone fracture is increased with canagliflozin treatment.

Individuals who experience side effects while taking canagliflozin should submit a report through the FDA’s MedWatch program, or contact 1-800-332-1088 for more information.

[email protected]

Interim safety results from an ongoing clinical trial found an increase in leg and foot amputations, mostly affecting the toes, in patients treated with the diabetes medicine canagliflozin, according to an FDA Drug Safety Communication on May 18, 2016.

The agency currently is investigating the safety issue but has yet to determine if taking canagliflozin is associated with an increased risk of leg and foot amputations. A sodium-glucose cotransporter 2 inhibitor, canagliflozin is marketed as Invokana and Invokamet by Janssen Pharmaceuticals, and was approved by the FDA in March 2013.

“Patients should not stop or change their diabetes medicines without first talking to their health care professional,” the communication states. “Doing so can lead to uncontrolled blood sugar levels that can be harmful. Over time, this can cause serious problems, including blindness, nerve and kidney damage, and heart disease. Patients taking canagliflozin should notify their health care professionals right away if they notice any new pain or tenderness, sores or ulcers, or infections in their legs or feet.”

The agency advises health care professionals to follow the recommendations in the canagliflozin drug labels and to monitor patients for the signs and symptoms described above.

Upon its approval, the FDA required five postmarketing studies for canagliflozin: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the Pediatric Research Equity Act (PREA), including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study. In late 2015, investigators determined that the risk of bone fracture is increased with canagliflozin treatment.

Individuals who experience side effects while taking canagliflozin should submit a report through the FDA’s MedWatch program, or contact 1-800-332-1088 for more information.

[email protected]

Interim safety results from an ongoing clinical trial found an increase in leg and foot amputations, mostly affecting the toes, in patients treated with the diabetes medicine canagliflozin, according to an FDA Drug Safety Communication on May 18, 2016.

The agency currently is investigating the safety issue but has yet to determine if taking canagliflozin is associated with an increased risk of leg and foot amputations. A sodium-glucose cotransporter 2 inhibitor, canagliflozin is marketed as Invokana and Invokamet by Janssen Pharmaceuticals, and was approved by the FDA in March 2013.

“Patients should not stop or change their diabetes medicines without first talking to their health care professional,” the communication states. “Doing so can lead to uncontrolled blood sugar levels that can be harmful. Over time, this can cause serious problems, including blindness, nerve and kidney damage, and heart disease. Patients taking canagliflozin should notify their health care professionals right away if they notice any new pain or tenderness, sores or ulcers, or infections in their legs or feet.”

The agency advises health care professionals to follow the recommendations in the canagliflozin drug labels and to monitor patients for the signs and symptoms described above.

Upon its approval, the FDA required five postmarketing studies for canagliflozin: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the Pediatric Research Equity Act (PREA), including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study. In late 2015, investigators determined that the risk of bone fracture is increased with canagliflozin treatment.

Individuals who experience side effects while taking canagliflozin should submit a report through the FDA’s MedWatch program, or contact 1-800-332-1088 for more information.

[email protected]

ATLANTA – Some patients experienced improvement in at least one neurocognitive domain up to 3 years after having bariatric surgery, a small, systematic review has shown.

The most significant improvements were reported in memory, with nine studies showing some statistically significant improvement in a post-bariatric surgery cohort. Four studies showed statistically significant improvement in attention and executive function, and two did so in language.

Dr. Gurneet S. Thiara, a psychiatry resident at the University of Toronto, presented the findings during a scientific session at this year’s annual meeting of the American Psychiatric Association.

Because the studies that form the basis of the analysis did not follow a standard pre-surgery neurocognitive assessment, the actual scope of bariatric surgery’s impact on neurocognition is hard to determine. This shortcoming provides evidence that instituting a standardized method of psychiatric assessment pre-bariatric surgery could help clinicians better anticipate overall neurocognitive outcomes, he said.

“It’s hard to pinpoint the one domain that affects [this cohort] most,” said Dr. Thiara.

One study included in the analysis showed no neurocognitive improvement, although Dr. Thiara noted this was possibly due to the under- or non-reporting of negative outcomes by researchers who conducted studies that might have met his inclusion criteria.

Dr. Thiara and his colleagues were not able to draw conclusions as to which patients would be affected in which domains and by what mechanism of action. Their analysis did suggest possible relationships between gastric bypass and changes in metabolism, levels of leptin and ghrelin, vascular function, hypoperfusion in the brain, and even shifts in the gut microbiome.

Dr. Thiara sought studies with bariatric surgery patients whose neurocognitive and psychological outcomes were followed anywhere from one to three years post-surgery. After analyzing 422 studies published between January 1990 and August 2015, only ten studies, with patient sample sizes ranging from 10 to 156, met the criteria.

The study was not intended to determine a relationship between neurocognitive outcomes and type of bypass surgery performed, but Dr. Thiara said the majority of the procedures analyzed tended to be Roux-en-Y rather than the gastric bypass sleeve.

[email protected]

On Twitter @whitneymcknight

ATLANTA – Some patients experienced improvement in at least one neurocognitive domain up to 3 years after having bariatric surgery, a small, systematic review has shown.

The most significant improvements were reported in memory, with nine studies showing some statistically significant improvement in a post-bariatric surgery cohort. Four studies showed statistically significant improvement in attention and executive function, and two did so in language.

Dr. Gurneet S. Thiara, a psychiatry resident at the University of Toronto, presented the findings during a scientific session at this year’s annual meeting of the American Psychiatric Association.

Because the studies that form the basis of the analysis did not follow a standard pre-surgery neurocognitive assessment, the actual scope of bariatric surgery’s impact on neurocognition is hard to determine. This shortcoming provides evidence that instituting a standardized method of psychiatric assessment pre-bariatric surgery could help clinicians better anticipate overall neurocognitive outcomes, he said.

“It’s hard to pinpoint the one domain that affects [this cohort] most,” said Dr. Thiara.

One study included in the analysis showed no neurocognitive improvement, although Dr. Thiara noted this was possibly due to the under- or non-reporting of negative outcomes by researchers who conducted studies that might have met his inclusion criteria.

Dr. Thiara and his colleagues were not able to draw conclusions as to which patients would be affected in which domains and by what mechanism of action. Their analysis did suggest possible relationships between gastric bypass and changes in metabolism, levels of leptin and ghrelin, vascular function, hypoperfusion in the brain, and even shifts in the gut microbiome.

Dr. Thiara sought studies with bariatric surgery patients whose neurocognitive and psychological outcomes were followed anywhere from one to three years post-surgery. After analyzing 422 studies published between January 1990 and August 2015, only ten studies, with patient sample sizes ranging from 10 to 156, met the criteria.

The study was not intended to determine a relationship between neurocognitive outcomes and type of bypass surgery performed, but Dr. Thiara said the majority of the procedures analyzed tended to be Roux-en-Y rather than the gastric bypass sleeve.

[email protected]

On Twitter @whitneymcknight

ATLANTA – Some patients experienced improvement in at least one neurocognitive domain up to 3 years after having bariatric surgery, a small, systematic review has shown.

The most significant improvements were reported in memory, with nine studies showing some statistically significant improvement in a post-bariatric surgery cohort. Four studies showed statistically significant improvement in attention and executive function, and two did so in language.

Dr. Gurneet S. Thiara, a psychiatry resident at the University of Toronto, presented the findings during a scientific session at this year’s annual meeting of the American Psychiatric Association.

Because the studies that form the basis of the analysis did not follow a standard pre-surgery neurocognitive assessment, the actual scope of bariatric surgery’s impact on neurocognition is hard to determine. This shortcoming provides evidence that instituting a standardized method of psychiatric assessment pre-bariatric surgery could help clinicians better anticipate overall neurocognitive outcomes, he said.

“It’s hard to pinpoint the one domain that affects [this cohort] most,” said Dr. Thiara.

One study included in the analysis showed no neurocognitive improvement, although Dr. Thiara noted this was possibly due to the under- or non-reporting of negative outcomes by researchers who conducted studies that might have met his inclusion criteria.

Dr. Thiara and his colleagues were not able to draw conclusions as to which patients would be affected in which domains and by what mechanism of action. Their analysis did suggest possible relationships between gastric bypass and changes in metabolism, levels of leptin and ghrelin, vascular function, hypoperfusion in the brain, and even shifts in the gut microbiome.

Dr. Thiara sought studies with bariatric surgery patients whose neurocognitive and psychological outcomes were followed anywhere from one to three years post-surgery. After analyzing 422 studies published between January 1990 and August 2015, only ten studies, with patient sample sizes ranging from 10 to 156, met the criteria.

The study was not intended to determine a relationship between neurocognitive outcomes and type of bypass surgery performed, but Dr. Thiara said the majority of the procedures analyzed tended to be Roux-en-Y rather than the gastric bypass sleeve.

[email protected]

On Twitter @whitneymcknight

Individuals whose blood pressure rose sharply over time had a significantly increased risk of stroke and death from nonstroke causes, compared with other blood pressure trajectories in a study of more than 6,000 adults published online May 9 in Hypertension.

The current association of blood pressure with stroke does not account for variations in blood pressure trajectories over the long term, wrote Dr. M. Arfan Ikram of Erasmus University, Rotterdam, the Netherlands, and his colleagues.

IPGGutenbergUKLtd/ThinkStock

The researchers reviewed data from 6,745 adults aged 55-106 years participating in the population-based Rotterdam Study, and identified four blood pressure trajectories over 5 decades. Class 1 included individuals whose blood pressure increased from 120 to 160 mm Hg; class 2 increased from 120 to 200 mm Hg; class 3 included those with moderate midlife blood pressure averaging 140 mm Hg; class 4 included those with a high midlife blood pressure averaging 160 mm Hg.

After controlling for confounding variables, class 3 had the highest overall risk of stroke, but the lowest risk of dying from a nonstroke event. Class 2 and class 4 individuals were at the greatest risk of stroke and of dying from nonstroke disease before 80 years of age. Class 1 individuals (with a normal baseline blood pressure and gradual increase) were least likely to suffer a stroke or die from a nonstroke event (Hypertension. 2016 May 9).

Although the study was limited by its homogenous nature (small geographical region, mostly white population), the findings show the importance of regular blood pressure measurement, the researchers noted.

“Identifying the patterns described in our study is an important step, since they evoke new causal and treatment questions that can motivate future studies to explore the etiologic significance and predictive value of associations,” they said. The researchers had no financial conflicts to disclose.

Individuals whose blood pressure rose sharply over time had a significantly increased risk of stroke and death from nonstroke causes, compared with other blood pressure trajectories in a study of more than 6,000 adults published online May 9 in Hypertension.

The current association of blood pressure with stroke does not account for variations in blood pressure trajectories over the long term, wrote Dr. M. Arfan Ikram of Erasmus University, Rotterdam, the Netherlands, and his colleagues.

IPGGutenbergUKLtd/ThinkStock

The researchers reviewed data from 6,745 adults aged 55-106 years participating in the population-based Rotterdam Study, and identified four blood pressure trajectories over 5 decades. Class 1 included individuals whose blood pressure increased from 120 to 160 mm Hg; class 2 increased from 120 to 200 mm Hg; class 3 included those with moderate midlife blood pressure averaging 140 mm Hg; class 4 included those with a high midlife blood pressure averaging 160 mm Hg.

After controlling for confounding variables, class 3 had the highest overall risk of stroke, but the lowest risk of dying from a nonstroke event. Class 2 and class 4 individuals were at the greatest risk of stroke and of dying from nonstroke disease before 80 years of age. Class 1 individuals (with a normal baseline blood pressure and gradual increase) were least likely to suffer a stroke or die from a nonstroke event (Hypertension. 2016 May 9).

Although the study was limited by its homogenous nature (small geographical region, mostly white population), the findings show the importance of regular blood pressure measurement, the researchers noted.

“Identifying the patterns described in our study is an important step, since they evoke new causal and treatment questions that can motivate future studies to explore the etiologic significance and predictive value of associations,” they said. The researchers had no financial conflicts to disclose.

Individuals whose blood pressure rose sharply over time had a significantly increased risk of stroke and death from nonstroke causes, compared with other blood pressure trajectories in a study of more than 6,000 adults published online May 9 in Hypertension.

The current association of blood pressure with stroke does not account for variations in blood pressure trajectories over the long term, wrote Dr. M. Arfan Ikram of Erasmus University, Rotterdam, the Netherlands, and his colleagues.

IPGGutenbergUKLtd/ThinkStock

The researchers reviewed data from 6,745 adults aged 55-106 years participating in the population-based Rotterdam Study, and identified four blood pressure trajectories over 5 decades. Class 1 included individuals whose blood pressure increased from 120 to 160 mm Hg; class 2 increased from 120 to 200 mm Hg; class 3 included those with moderate midlife blood pressure averaging 140 mm Hg; class 4 included those with a high midlife blood pressure averaging 160 mm Hg.

After controlling for confounding variables, class 3 had the highest overall risk of stroke, but the lowest risk of dying from a nonstroke event. Class 2 and class 4 individuals were at the greatest risk of stroke and of dying from nonstroke disease before 80 years of age. Class 1 individuals (with a normal baseline blood pressure and gradual increase) were least likely to suffer a stroke or die from a nonstroke event (Hypertension. 2016 May 9).

Although the study was limited by its homogenous nature (small geographical region, mostly white population), the findings show the importance of regular blood pressure measurement, the researchers noted.

“Identifying the patterns described in our study is an important step, since they evoke new causal and treatment questions that can motivate future studies to explore the etiologic significance and predictive value of associations,” they said. The researchers had no financial conflicts to disclose.

Neither saxagliptin nor sitagliptin, the two oral DPP-4 inhibitors most commonly used as antihyperglycemic medications, raised the risk of hospitalization for heart failure in a large population-based cohort study that analyzed data from a Food and Drug Administration surveillance program.

The report was published online April 25 in Annals of Internal Medicine.

The cardiovascular safety of DPP-4 inhibitors is controversial: Several postmarketing studies have produced conflicting results, particularly with regard to HF risk. “Patients with diabetes have a higher HF risk than those without, so any antihyperglycemic agent that modifies the risk warrants further examination,” said Sengwee Toh, Sc.D., a pharmacoepidemiologist in the department of population medicine, Harvard Medical School and Harvard Pilgrim Health Institute, Boston, and his associates.

They compared rates of HF among demographically and geographically diverse patients who initiated antidiabetic medications during a 7-year period in routine clinical settings. The study population included 78,553 adults who initiated saxagliptin and 298,124 who initiated sitagliptin, who were compared with patients who initiated pioglitazone, second-generation sulfonylureas, or long-acting insulins. Mean follow-up was 7-9 months.

There was no evidence of an increased risk of hospitalization for HF among new users of saxagliptin or sitagliptin. The hazard ratios for developing HF were 0.83 for saxagliptin vs. sitagliptin, 0.63 for saxagliptin vs. pioglitazone, 0.69 for saxagliptin vs. sulfonylureas, and 0.61 for saxagliptin vs. insulin. Similarly, the hazard ratios for developing HF were 0.74 for sitagliptin vs. pioglitazone, 0.86 for sitagliptin vs. sulfonylureas, and 0.71 for sitagliptin vs. insulin.

These results were consistent across sensitivity analyses and subgroup analyses that categorized patients by whether or not they had preexisting cardiovascular disease and whether or not they had a history of prior HF, the investigators said (Ann Intern Med. 2016 April 25. doi:10.7326/M15-2568).

However, this was an observational study with a relatively short follow-up. “Well-designed randomized trials with hospitalization for HF as the main endpoint or observational studies that address the limitations of our study will help provide more definitive evidence on the topic,” Dr. Toh and his associates said.

This study was supported by the FDA. Dr. Toh reported having no relevant financial disclosures; one of his associates reported receiving personal fees from Novartis unrelated to this work.

Neither saxagliptin nor sitagliptin, the two oral DPP-4 inhibitors most commonly used as antihyperglycemic medications, raised the risk of hospitalization for heart failure in a large population-based cohort study that analyzed data from a Food and Drug Administration surveillance program.

The report was published online April 25 in Annals of Internal Medicine.

The cardiovascular safety of DPP-4 inhibitors is controversial: Several postmarketing studies have produced conflicting results, particularly with regard to HF risk. “Patients with diabetes have a higher HF risk than those without, so any antihyperglycemic agent that modifies the risk warrants further examination,” said Sengwee Toh, Sc.D., a pharmacoepidemiologist in the department of population medicine, Harvard Medical School and Harvard Pilgrim Health Institute, Boston, and his associates.

They compared rates of HF among demographically and geographically diverse patients who initiated antidiabetic medications during a 7-year period in routine clinical settings. The study population included 78,553 adults who initiated saxagliptin and 298,124 who initiated sitagliptin, who were compared with patients who initiated pioglitazone, second-generation sulfonylureas, or long-acting insulins. Mean follow-up was 7-9 months.

There was no evidence of an increased risk of hospitalization for HF among new users of saxagliptin or sitagliptin. The hazard ratios for developing HF were 0.83 for saxagliptin vs. sitagliptin, 0.63 for saxagliptin vs. pioglitazone, 0.69 for saxagliptin vs. sulfonylureas, and 0.61 for saxagliptin vs. insulin. Similarly, the hazard ratios for developing HF were 0.74 for sitagliptin vs. pioglitazone, 0.86 for sitagliptin vs. sulfonylureas, and 0.71 for sitagliptin vs. insulin.

These results were consistent across sensitivity analyses and subgroup analyses that categorized patients by whether or not they had preexisting cardiovascular disease and whether or not they had a history of prior HF, the investigators said (Ann Intern Med. 2016 April 25. doi:10.7326/M15-2568).

However, this was an observational study with a relatively short follow-up. “Well-designed randomized trials with hospitalization for HF as the main endpoint or observational studies that address the limitations of our study will help provide more definitive evidence on the topic,” Dr. Toh and his associates said.

This study was supported by the FDA. Dr. Toh reported having no relevant financial disclosures; one of his associates reported receiving personal fees from Novartis unrelated to this work.

Neither saxagliptin nor sitagliptin, the two oral DPP-4 inhibitors most commonly used as antihyperglycemic medications, raised the risk of hospitalization for heart failure in a large population-based cohort study that analyzed data from a Food and Drug Administration surveillance program.

The report was published online April 25 in Annals of Internal Medicine.

The cardiovascular safety of DPP-4 inhibitors is controversial: Several postmarketing studies have produced conflicting results, particularly with regard to HF risk. “Patients with diabetes have a higher HF risk than those without, so any antihyperglycemic agent that modifies the risk warrants further examination,” said Sengwee Toh, Sc.D., a pharmacoepidemiologist in the department of population medicine, Harvard Medical School and Harvard Pilgrim Health Institute, Boston, and his associates.

They compared rates of HF among demographically and geographically diverse patients who initiated antidiabetic medications during a 7-year period in routine clinical settings. The study population included 78,553 adults who initiated saxagliptin and 298,124 who initiated sitagliptin, who were compared with patients who initiated pioglitazone, second-generation sulfonylureas, or long-acting insulins. Mean follow-up was 7-9 months.

There was no evidence of an increased risk of hospitalization for HF among new users of saxagliptin or sitagliptin. The hazard ratios for developing HF were 0.83 for saxagliptin vs. sitagliptin, 0.63 for saxagliptin vs. pioglitazone, 0.69 for saxagliptin vs. sulfonylureas, and 0.61 for saxagliptin vs. insulin. Similarly, the hazard ratios for developing HF were 0.74 for sitagliptin vs. pioglitazone, 0.86 for sitagliptin vs. sulfonylureas, and 0.71 for sitagliptin vs. insulin.

These results were consistent across sensitivity analyses and subgroup analyses that categorized patients by whether or not they had preexisting cardiovascular disease and whether or not they had a history of prior HF, the investigators said (Ann Intern Med. 2016 April 25. doi:10.7326/M15-2568).

However, this was an observational study with a relatively short follow-up. “Well-designed randomized trials with hospitalization for HF as the main endpoint or observational studies that address the limitations of our study will help provide more definitive evidence on the topic,” Dr. Toh and his associates said.

This study was supported by the FDA. Dr. Toh reported having no relevant financial disclosures; one of his associates reported receiving personal fees from Novartis unrelated to this work.

CHICAGO – The superiority of metabolic surgery over intensive medical therapy for achieving glycemic control in patients with type 2 diabetes was largely maintained at the final 5-year follow-up evaluation in the randomized, controlled STAMPEDE trial.

The 150 subjects, who had “fairly severe diabetes” with an average disease duration of 8 years, were randomized to receive intensive medical therapy alone, or intensive medical therapy with Roux-en-Y gastric bypass surgery or sleeve gastrectomy surgery. The primary endpoint of hemoglobin A_1c less than 6% was achieved in 5%, 29%, and 23% of patients in the groups, respectively. The difference was statistically significant in favor of both types of surgery, Dr. Philip Raymond Schauer reported at the annual meeting of the American College of Cardiology.

Furthermore, patients in the surgery groups fared better than those in the intensive medical therapy group on several other measures, including disease remission (defied as HbA_1c less than 6% without diabetes medication), HbA_1c less than 7% (the American Diabetes Association target for therapy), change in fasting plasma glucose from baseline, and changes in high- and low-density lipoprotein cholesterol levels, said Dr. Schauer, director of the Cleveland Clinic Bariatric and Metabolic Institute.

Patients in the surgery groups also experienced a significantly greater reduction in the use of antihypertensive medications and lipid-lowering agents, he added.

The “very dramatic drop” in HbA_1c seen early on in the surgical patients was, for the most part, sustained out to 5 years, he said.

The results for both surgeries were significantly better than those for intensive medical therapy, but the results with gastric bypass were more effective at 5 years than were those for sleeve gastrectomy, he added, noting that the surgery patients had better quality of life, compared with the intensive medical therapy patients.

As for adverse events in the surgery groups, no perioperative deaths occurred, and while there were some surgical complications, none resulted in long-term disability, Dr. Schauer said.

Anemia was more common in the surgery patients, but was fairly mild. The most common complication was weight gain in 20% of patients, and the overall reoperation rate was 7%.

Of note, patients in the study had body mass index ranging from 27 to 43 kg/m², and those with BMI less than 35 had similar benefits as those with more severe obesity. This is important, as many insurance companies won’t cover metabolic surgery for patients with BMI less than 35, he explained.

These findings represent the longest follow-up to date comparing the efficacy of the two most common metabolic surgery procedures with medical treatment of type 2 diabetes for maintaining glycemic control or reducing end-organ complications. Three-year outcomes of STAMPEDE (Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently) were reported in 2014 (N Engl J Med. 2014;370:2002-13).

The participants ranged in age from 20 to 60 years. The average HbA_1c was about 9%, the average BMI was 36, and most were on at least three antidiabetic medications at baseline. Half were on insulin.

The findings are important, because of the roughly 25 million Americans with type 2 diabetes, only about half have good glycemic control on their current medical treatment strategies, Dr. Schauer said.

Though limited by the single-center study design, the STAMPEDE findings show that metabolic surgery is more effective long term than intensive medical therapy in patients with uncontrolled type 2 diabetes and should be considered a treatment option in this population, he concluded, adding that multicenter studies would be helpful for determining the generalizability of the findings.

Dr. Schauer reported receiving consulting fees/honoraria from Ethicon Endosurgery and The Medicines Company, and having ownership interest in Surgical Excellence.

[email protected]

CHICAGO – The superiority of metabolic surgery over intensive medical therapy for achieving glycemic control in patients with type 2 diabetes was largely maintained at the final 5-year follow-up evaluation in the randomized, controlled STAMPEDE trial.

The 150 subjects, who had “fairly severe diabetes” with an average disease duration of 8 years, were randomized to receive intensive medical therapy alone, or intensive medical therapy with Roux-en-Y gastric bypass surgery or sleeve gastrectomy surgery. The primary endpoint of hemoglobin A_1c less than 6% was achieved in 5%, 29%, and 23% of patients in the groups, respectively. The difference was statistically significant in favor of both types of surgery, Dr. Philip Raymond Schauer reported at the annual meeting of the American College of Cardiology.

Furthermore, patients in the surgery groups fared better than those in the intensive medical therapy group on several other measures, including disease remission (defied as HbA_1c less than 6% without diabetes medication), HbA_1c less than 7% (the American Diabetes Association target for therapy), change in fasting plasma glucose from baseline, and changes in high- and low-density lipoprotein cholesterol levels, said Dr. Schauer, director of the Cleveland Clinic Bariatric and Metabolic Institute.

Patients in the surgery groups also experienced a significantly greater reduction in the use of antihypertensive medications and lipid-lowering agents, he added.

The “very dramatic drop” in HbA_1c seen early on in the surgical patients was, for the most part, sustained out to 5 years, he said.

The results for both surgeries were significantly better than those for intensive medical therapy, but the results with gastric bypass were more effective at 5 years than were those for sleeve gastrectomy, he added, noting that the surgery patients had better quality of life, compared with the intensive medical therapy patients.

As for adverse events in the surgery groups, no perioperative deaths occurred, and while there were some surgical complications, none resulted in long-term disability, Dr. Schauer said.

Anemia was more common in the surgery patients, but was fairly mild. The most common complication was weight gain in 20% of patients, and the overall reoperation rate was 7%.

Of note, patients in the study had body mass index ranging from 27 to 43 kg/m², and those with BMI less than 35 had similar benefits as those with more severe obesity. This is important, as many insurance companies won’t cover metabolic surgery for patients with BMI less than 35, he explained.

These findings represent the longest follow-up to date comparing the efficacy of the two most common metabolic surgery procedures with medical treatment of type 2 diabetes for maintaining glycemic control or reducing end-organ complications. Three-year outcomes of STAMPEDE (Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently) were reported in 2014 (N Engl J Med. 2014;370:2002-13).

The participants ranged in age from 20 to 60 years. The average HbA_1c was about 9%, the average BMI was 36, and most were on at least three antidiabetic medications at baseline. Half were on insulin.

The findings are important, because of the roughly 25 million Americans with type 2 diabetes, only about half have good glycemic control on their current medical treatment strategies, Dr. Schauer said.

Though limited by the single-center study design, the STAMPEDE findings show that metabolic surgery is more effective long term than intensive medical therapy in patients with uncontrolled type 2 diabetes and should be considered a treatment option in this population, he concluded, adding that multicenter studies would be helpful for determining the generalizability of the findings.

Dr. Schauer reported receiving consulting fees/honoraria from Ethicon Endosurgery and The Medicines Company, and having ownership interest in Surgical Excellence.

[email protected]

CHICAGO – The superiority of metabolic surgery over intensive medical therapy for achieving glycemic control in patients with type 2 diabetes was largely maintained at the final 5-year follow-up evaluation in the randomized, controlled STAMPEDE trial.

The 150 subjects, who had “fairly severe diabetes” with an average disease duration of 8 years, were randomized to receive intensive medical therapy alone, or intensive medical therapy with Roux-en-Y gastric bypass surgery or sleeve gastrectomy surgery. The primary endpoint of hemoglobin A_1c less than 6% was achieved in 5%, 29%, and 23% of patients in the groups, respectively. The difference was statistically significant in favor of both types of surgery, Dr. Philip Raymond Schauer reported at the annual meeting of the American College of Cardiology.

Furthermore, patients in the surgery groups fared better than those in the intensive medical therapy group on several other measures, including disease remission (defied as HbA_1c less than 6% without diabetes medication), HbA_1c less than 7% (the American Diabetes Association target for therapy), change in fasting plasma glucose from baseline, and changes in high- and low-density lipoprotein cholesterol levels, said Dr. Schauer, director of the Cleveland Clinic Bariatric and Metabolic Institute.

Patients in the surgery groups also experienced a significantly greater reduction in the use of antihypertensive medications and lipid-lowering agents, he added.

The “very dramatic drop” in HbA_1c seen early on in the surgical patients was, for the most part, sustained out to 5 years, he said.

The results for both surgeries were significantly better than those for intensive medical therapy, but the results with gastric bypass were more effective at 5 years than were those for sleeve gastrectomy, he added, noting that the surgery patients had better quality of life, compared with the intensive medical therapy patients.

As for adverse events in the surgery groups, no perioperative deaths occurred, and while there were some surgical complications, none resulted in long-term disability, Dr. Schauer said.

Anemia was more common in the surgery patients, but was fairly mild. The most common complication was weight gain in 20% of patients, and the overall reoperation rate was 7%.

Of note, patients in the study had body mass index ranging from 27 to 43 kg/m², and those with BMI less than 35 had similar benefits as those with more severe obesity. This is important, as many insurance companies won’t cover metabolic surgery for patients with BMI less than 35, he explained.

These findings represent the longest follow-up to date comparing the efficacy of the two most common metabolic surgery procedures with medical treatment of type 2 diabetes for maintaining glycemic control or reducing end-organ complications. Three-year outcomes of STAMPEDE (Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently) were reported in 2014 (N Engl J Med. 2014;370:2002-13).

The participants ranged in age from 20 to 60 years. The average HbA_1c was about 9%, the average BMI was 36, and most were on at least three antidiabetic medications at baseline. Half were on insulin.

The findings are important, because of the roughly 25 million Americans with type 2 diabetes, only about half have good glycemic control on their current medical treatment strategies, Dr. Schauer said.

Though limited by the single-center study design, the STAMPEDE findings show that metabolic surgery is more effective long term than intensive medical therapy in patients with uncontrolled type 2 diabetes and should be considered a treatment option in this population, he concluded, adding that multicenter studies would be helpful for determining the generalizability of the findings.

Dr. Schauer reported receiving consulting fees/honoraria from Ethicon Endosurgery and The Medicines Company, and having ownership interest in Surgical Excellence.

[email protected]