Diabetes Hub

Janssen has announced that it has submitted a supplemental new drug application to the Food and Drug Administration to add an indication for canagliflozin (Invokana). The sodium-glucose cotransporter 2 is currently indicated, in addition to diet and exercise, for glycemic control in type 2 diabetes. However, the new indication would be for the treatment of patients with both type 2 diabetes and chronic kidney disease in hopes of reducing the risks of end-stage kidney disease and of renal or cardiovascular death, according to a press release from the manufacturer.

If approved, canagliflozin will be the first diabetes medicine for the treatment of people living with type 2 diabetes and chronic kidney disease, according to the press release.

The application was based on the results of the phase 3 CREDENCE trial, a randomized, double-blind, placebo-controlled, multicenter study of 4,401 patients with type 2 diabetes, stage 2 or 3 chronic kidney disease, and macroalbuminuria. The patients received standard of care as well. The trial was stopped early, in July 2018, because it had met the prespecified criteria for efficacy. Data from the trial will be presented in mid-April at the annual meeting of the International Society of Nephrology World Congress of Nephrology in Melbourne.

Canagliflozin is contraindicated in patients with severe renal impairment (an estimated glomerular filtration rate of less than 30 mL/min per 1.73 m²), patients with end-stage renal disease, or patients on dialysis. Serious side effects associated with canagliflozin include ketoacidosis, kidney problems, hyperkalemia, serious urinary tract infections, and hypoglycemia. The most common side effects are yeast infections of the vagina or penis, and changes in urination.

The full prescribing information for canagliflozin is available on the FDA website.

[email protected]

Janssen has announced that it has submitted a supplemental new drug application to the Food and Drug Administration to add an indication for canagliflozin (Invokana). The sodium-glucose cotransporter 2 is currently indicated, in addition to diet and exercise, for glycemic control in type 2 diabetes. However, the new indication would be for the treatment of patients with both type 2 diabetes and chronic kidney disease in hopes of reducing the risks of end-stage kidney disease and of renal or cardiovascular death, according to a press release from the manufacturer.

If approved, canagliflozin will be the first diabetes medicine for the treatment of people living with type 2 diabetes and chronic kidney disease, according to the press release.

The application was based on the results of the phase 3 CREDENCE trial, a randomized, double-blind, placebo-controlled, multicenter study of 4,401 patients with type 2 diabetes, stage 2 or 3 chronic kidney disease, and macroalbuminuria. The patients received standard of care as well. The trial was stopped early, in July 2018, because it had met the prespecified criteria for efficacy. Data from the trial will be presented in mid-April at the annual meeting of the International Society of Nephrology World Congress of Nephrology in Melbourne.

Canagliflozin is contraindicated in patients with severe renal impairment (an estimated glomerular filtration rate of less than 30 mL/min per 1.73 m²), patients with end-stage renal disease, or patients on dialysis. Serious side effects associated with canagliflozin include ketoacidosis, kidney problems, hyperkalemia, serious urinary tract infections, and hypoglycemia. The most common side effects are yeast infections of the vagina or penis, and changes in urination.

The full prescribing information for canagliflozin is available on the FDA website.

[email protected]

Janssen has announced that it has submitted a supplemental new drug application to the Food and Drug Administration to add an indication for canagliflozin (Invokana). The sodium-glucose cotransporter 2 is currently indicated, in addition to diet and exercise, for glycemic control in type 2 diabetes. However, the new indication would be for the treatment of patients with both type 2 diabetes and chronic kidney disease in hopes of reducing the risks of end-stage kidney disease and of renal or cardiovascular death, according to a press release from the manufacturer.

If approved, canagliflozin will be the first diabetes medicine for the treatment of people living with type 2 diabetes and chronic kidney disease, according to the press release.

The application was based on the results of the phase 3 CREDENCE trial, a randomized, double-blind, placebo-controlled, multicenter study of 4,401 patients with type 2 diabetes, stage 2 or 3 chronic kidney disease, and macroalbuminuria. The patients received standard of care as well. The trial was stopped early, in July 2018, because it had met the prespecified criteria for efficacy. Data from the trial will be presented in mid-April at the annual meeting of the International Society of Nephrology World Congress of Nephrology in Melbourne.

Canagliflozin is contraindicated in patients with severe renal impairment (an estimated glomerular filtration rate of less than 30 mL/min per 1.73 m²), patients with end-stage renal disease, or patients on dialysis. Serious side effects associated with canagliflozin include ketoacidosis, kidney problems, hyperkalemia, serious urinary tract infections, and hypoglycemia. The most common side effects are yeast infections of the vagina or penis, and changes in urination.

The full prescribing information for canagliflozin is available on the FDA website.

[email protected]

The two newer classes of antihyperglycemic drugs that lower cardiovascular risk have different effects on specific cardiovascular and kidney disease outcomes in patients with type 2 diabetes, results of a meta-analysis suggest. Sodium-glucose contransporter-2 (SGLT2) inhibitors significantly reduced hospitalization from heart failure, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not, according to the reported results.

The GLP-1–RA class reduced risk of kidney disease progression, largely driven by a reduction in macroalbuminuria, according to the authors, whereas only the SGLT2 inhibitors reduced adverse kidney disease outcomes in a composite excluding that biomarker.

“The prevention of heart failure and progression of kidney disease by SGLT2 [inhibitors] should be considered in the decision-making process when treating patients with type 2 diabetes,” study senior author Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital, Boston, and his coauthors wrote in a report on the study appearing in Circulation.

Both GLP-1 RAs and SGLT2 inhibitors significantly reduced major adverse cardiovascular events (MACE) and, as shown in other recent findings, their benefits were confined to patients with established atherosclerotic cardiovascular disease, Dr. Sabatine and his colleagues wrote.

The systematic review and meta-analysis of eight cardiovascular outcomes trials included 77,242 patients, of whom about 56% participated in GLP-1–RA studies and 44% in SGLT2-inhibitor trials. Just under three-quarters of the patients had established atherosclerotic cardiovascular disease, while the remainder had multiple risk factors for it.

Relative risk of hospitalization for heart failure was reduced by 31% with SGLT2 inhibitors, but it was not significantly reduced by GLP-1 RAs, the authors noted.

Risk of kidney disease progression was reduced by 38% with SGLT2 inhibitors and by 18% with GLP-1 RAs when the researchers used a broad composite endpoint including macroalbuminuria, estimated glomerular filtration rate (eGFR), end-stage kidney disease, and death due to renal causes.

By contrast, SGLT2 inhibitors reduced by 45% the relative risk of a narrower kidney outcome that excluded macroalbuminuria, whereas GLP-1 RAs had only a nonsignificant effect on the risk of doubling serum creatinine. That suggests the relative risk reduction of the kidney composite with GLP-1 RAs was driven mainly by a reduction in macroalbuminuria, the authors wrote.

Although albuminuria is an established biomarker for kidney and cardiovascular disease, it is a surrogate marker and can even be absent in patients with reduced eGFR, they said.

“Reduction in eGFR has emerged as a more meaningful endpoint of greater importance and is used in ongoing diabetes trials for kidney outcomes,” the authors said in a discussion of their results.

Relative risk of the composite MACE endpoint, including myocardial infarction, stroke, and cardiovascular death, was reduced by 12% for GLP-1 RAs and by 11% for SGLT2 [inhibitors], according to results of the analysis. However, the benefit was confined to patients with established cardiovascular disease, who had a 14% reduction of risk, compared with no treatment effect in patients who had multiple risk factors only.

Looking at individual MACE components, investigators found that both drug classes significantly reduced relative risk of myocardial infarction and of cardiovascular death, whereas only GLP-1 RAs significantly reduced relative risk of stroke.

Study authors provided disclosures related to AstraZeneca, Amgen, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, and Medimmune, among others.

SOURCE: Zelniker TA et al. Circulation. 2019 Feb 21. doi: 10.1161/CIRCULATIONAHA.118.038868.

The two newer classes of antihyperglycemic drugs that lower cardiovascular risk have different effects on specific cardiovascular and kidney disease outcomes in patients with type 2 diabetes, results of a meta-analysis suggest. Sodium-glucose contransporter-2 (SGLT2) inhibitors significantly reduced hospitalization from heart failure, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not, according to the reported results.

The GLP-1–RA class reduced risk of kidney disease progression, largely driven by a reduction in macroalbuminuria, according to the authors, whereas only the SGLT2 inhibitors reduced adverse kidney disease outcomes in a composite excluding that biomarker.

“The prevention of heart failure and progression of kidney disease by SGLT2 [inhibitors] should be considered in the decision-making process when treating patients with type 2 diabetes,” study senior author Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital, Boston, and his coauthors wrote in a report on the study appearing in Circulation.

Both GLP-1 RAs and SGLT2 inhibitors significantly reduced major adverse cardiovascular events (MACE) and, as shown in other recent findings, their benefits were confined to patients with established atherosclerotic cardiovascular disease, Dr. Sabatine and his colleagues wrote.

The systematic review and meta-analysis of eight cardiovascular outcomes trials included 77,242 patients, of whom about 56% participated in GLP-1–RA studies and 44% in SGLT2-inhibitor trials. Just under three-quarters of the patients had established atherosclerotic cardiovascular disease, while the remainder had multiple risk factors for it.

Relative risk of hospitalization for heart failure was reduced by 31% with SGLT2 inhibitors, but it was not significantly reduced by GLP-1 RAs, the authors noted.

Risk of kidney disease progression was reduced by 38% with SGLT2 inhibitors and by 18% with GLP-1 RAs when the researchers used a broad composite endpoint including macroalbuminuria, estimated glomerular filtration rate (eGFR), end-stage kidney disease, and death due to renal causes.

By contrast, SGLT2 inhibitors reduced by 45% the relative risk of a narrower kidney outcome that excluded macroalbuminuria, whereas GLP-1 RAs had only a nonsignificant effect on the risk of doubling serum creatinine. That suggests the relative risk reduction of the kidney composite with GLP-1 RAs was driven mainly by a reduction in macroalbuminuria, the authors wrote.

Although albuminuria is an established biomarker for kidney and cardiovascular disease, it is a surrogate marker and can even be absent in patients with reduced eGFR, they said.

“Reduction in eGFR has emerged as a more meaningful endpoint of greater importance and is used in ongoing diabetes trials for kidney outcomes,” the authors said in a discussion of their results.

Relative risk of the composite MACE endpoint, including myocardial infarction, stroke, and cardiovascular death, was reduced by 12% for GLP-1 RAs and by 11% for SGLT2 [inhibitors], according to results of the analysis. However, the benefit was confined to patients with established cardiovascular disease, who had a 14% reduction of risk, compared with no treatment effect in patients who had multiple risk factors only.

Looking at individual MACE components, investigators found that both drug classes significantly reduced relative risk of myocardial infarction and of cardiovascular death, whereas only GLP-1 RAs significantly reduced relative risk of stroke.

Study authors provided disclosures related to AstraZeneca, Amgen, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, and Medimmune, among others.

SOURCE: Zelniker TA et al. Circulation. 2019 Feb 21. doi: 10.1161/CIRCULATIONAHA.118.038868.

The two newer classes of antihyperglycemic drugs that lower cardiovascular risk have different effects on specific cardiovascular and kidney disease outcomes in patients with type 2 diabetes, results of a meta-analysis suggest. Sodium-glucose contransporter-2 (SGLT2) inhibitors significantly reduced hospitalization from heart failure, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not, according to the reported results.

The GLP-1–RA class reduced risk of kidney disease progression, largely driven by a reduction in macroalbuminuria, according to the authors, whereas only the SGLT2 inhibitors reduced adverse kidney disease outcomes in a composite excluding that biomarker.

“The prevention of heart failure and progression of kidney disease by SGLT2 [inhibitors] should be considered in the decision-making process when treating patients with type 2 diabetes,” study senior author Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital, Boston, and his coauthors wrote in a report on the study appearing in Circulation.

Both GLP-1 RAs and SGLT2 inhibitors significantly reduced major adverse cardiovascular events (MACE) and, as shown in other recent findings, their benefits were confined to patients with established atherosclerotic cardiovascular disease, Dr. Sabatine and his colleagues wrote.

The systematic review and meta-analysis of eight cardiovascular outcomes trials included 77,242 patients, of whom about 56% participated in GLP-1–RA studies and 44% in SGLT2-inhibitor trials. Just under three-quarters of the patients had established atherosclerotic cardiovascular disease, while the remainder had multiple risk factors for it.

Relative risk of hospitalization for heart failure was reduced by 31% with SGLT2 inhibitors, but it was not significantly reduced by GLP-1 RAs, the authors noted.

Risk of kidney disease progression was reduced by 38% with SGLT2 inhibitors and by 18% with GLP-1 RAs when the researchers used a broad composite endpoint including macroalbuminuria, estimated glomerular filtration rate (eGFR), end-stage kidney disease, and death due to renal causes.

By contrast, SGLT2 inhibitors reduced by 45% the relative risk of a narrower kidney outcome that excluded macroalbuminuria, whereas GLP-1 RAs had only a nonsignificant effect on the risk of doubling serum creatinine. That suggests the relative risk reduction of the kidney composite with GLP-1 RAs was driven mainly by a reduction in macroalbuminuria, the authors wrote.

Although albuminuria is an established biomarker for kidney and cardiovascular disease, it is a surrogate marker and can even be absent in patients with reduced eGFR, they said.

“Reduction in eGFR has emerged as a more meaningful endpoint of greater importance and is used in ongoing diabetes trials for kidney outcomes,” the authors said in a discussion of their results.

Relative risk of the composite MACE endpoint, including myocardial infarction, stroke, and cardiovascular death, was reduced by 12% for GLP-1 RAs and by 11% for SGLT2 [inhibitors], according to results of the analysis. However, the benefit was confined to patients with established cardiovascular disease, who had a 14% reduction of risk, compared with no treatment effect in patients who had multiple risk factors only.

Looking at individual MACE components, investigators found that both drug classes significantly reduced relative risk of myocardial infarction and of cardiovascular death, whereas only GLP-1 RAs significantly reduced relative risk of stroke.

Study authors provided disclosures related to AstraZeneca, Amgen, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, and Medimmune, among others.

SOURCE: Zelniker TA et al. Circulation. 2019 Feb 21. doi: 10.1161/CIRCULATIONAHA.118.038868.

Adding once-weekly treatment with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide helped most patients with type 2 diabetes already being treated with sodium-glucose cotransporter-2 (SGLT2) inhibitors meet their glycemic targets and lose weight, researchers reported.

“Combining the distinct modes of action of these two drug classes has beneficial effects on glucose and weight outcomes,” wrote Bernard Zinman, MD, of Mount Sinai Hospital, Toronto, and his coauthors. Their report is in Lancet Diabetes and Endocrinology.

In the international, double-blind, phase 3 SUSTAIN 9 trial, 302 patients with type 2 diabetes whose hemoglobin A_{1c (}HbA_1c) levels were 7.0% to 10.0% (53 to 86 mmol/mol) despite at least 90 days of SGLT2-inhibitor therapy (alone or with metformin or sulfonylurea) were randomly assigned to add either once-weekly semaglutide (1-mg injection) or placebo to their regimen.

A total of 294 patients completed the trial. After 30 weeks, those who had received adjunctive semaglutide had significantly greater reductions in their HbA_1c levels (estimated treatment difference, –1.42%; P less than .0001). They also lost about 3.81 kg more bodyweight than did patients in the placebo group and they had significantly greater reductions in mean body mass index, waist circumference, fasting and self-measured blood glucose, systolic blood pressure, pulse rate, total cholesterol, and low-density lipoprotein and triglyceride levels.

The most commonly reported adverse effects of semaglutide were nausea, diarrhea, vomiting, and constipation, which were usually mild in severity. Severe or blood-glucose–confirmed hypoglycemia occurred in 2.7% patients on semaglutide and none on placebo. However, most patients who received semaglutide achieved an HbA_1c of 7.0% (53 mmol/mol) or less without weight gain or severe or blood-glucose–confirmed hypoglycemia (P less than .0001 vs. placebo).

Novo Nordisk funded the study. Three of the authors were employees of Novo Nordisk at the time of the study, and the remaining authors reported that they and/or their institutions had received funding from the company.

SOURCE: Zinman B et al. Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587(19)30066-X.

Adding once-weekly treatment with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide helped most patients with type 2 diabetes already being treated with sodium-glucose cotransporter-2 (SGLT2) inhibitors meet their glycemic targets and lose weight, researchers reported.

“Combining the distinct modes of action of these two drug classes has beneficial effects on glucose and weight outcomes,” wrote Bernard Zinman, MD, of Mount Sinai Hospital, Toronto, and his coauthors. Their report is in Lancet Diabetes and Endocrinology.

In the international, double-blind, phase 3 SUSTAIN 9 trial, 302 patients with type 2 diabetes whose hemoglobin A_{1c (}HbA_1c) levels were 7.0% to 10.0% (53 to 86 mmol/mol) despite at least 90 days of SGLT2-inhibitor therapy (alone or with metformin or sulfonylurea) were randomly assigned to add either once-weekly semaglutide (1-mg injection) or placebo to their regimen.

A total of 294 patients completed the trial. After 30 weeks, those who had received adjunctive semaglutide had significantly greater reductions in their HbA_1c levels (estimated treatment difference, –1.42%; P less than .0001). They also lost about 3.81 kg more bodyweight than did patients in the placebo group and they had significantly greater reductions in mean body mass index, waist circumference, fasting and self-measured blood glucose, systolic blood pressure, pulse rate, total cholesterol, and low-density lipoprotein and triglyceride levels.

The most commonly reported adverse effects of semaglutide were nausea, diarrhea, vomiting, and constipation, which were usually mild in severity. Severe or blood-glucose–confirmed hypoglycemia occurred in 2.7% patients on semaglutide and none on placebo. However, most patients who received semaglutide achieved an HbA_1c of 7.0% (53 mmol/mol) or less without weight gain or severe or blood-glucose–confirmed hypoglycemia (P less than .0001 vs. placebo).

Novo Nordisk funded the study. Three of the authors were employees of Novo Nordisk at the time of the study, and the remaining authors reported that they and/or their institutions had received funding from the company.

SOURCE: Zinman B et al. Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587(19)30066-X.

Adding once-weekly treatment with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide helped most patients with type 2 diabetes already being treated with sodium-glucose cotransporter-2 (SGLT2) inhibitors meet their glycemic targets and lose weight, researchers reported.

“Combining the distinct modes of action of these two drug classes has beneficial effects on glucose and weight outcomes,” wrote Bernard Zinman, MD, of Mount Sinai Hospital, Toronto, and his coauthors. Their report is in Lancet Diabetes and Endocrinology.

In the international, double-blind, phase 3 SUSTAIN 9 trial, 302 patients with type 2 diabetes whose hemoglobin A_{1c (}HbA_1c) levels were 7.0% to 10.0% (53 to 86 mmol/mol) despite at least 90 days of SGLT2-inhibitor therapy (alone or with metformin or sulfonylurea) were randomly assigned to add either once-weekly semaglutide (1-mg injection) or placebo to their regimen.

A total of 294 patients completed the trial. After 30 weeks, those who had received adjunctive semaglutide had significantly greater reductions in their HbA_1c levels (estimated treatment difference, –1.42%; P less than .0001). They also lost about 3.81 kg more bodyweight than did patients in the placebo group and they had significantly greater reductions in mean body mass index, waist circumference, fasting and self-measured blood glucose, systolic blood pressure, pulse rate, total cholesterol, and low-density lipoprotein and triglyceride levels.

The most commonly reported adverse effects of semaglutide were nausea, diarrhea, vomiting, and constipation, which were usually mild in severity. Severe or blood-glucose–confirmed hypoglycemia occurred in 2.7% patients on semaglutide and none on placebo. However, most patients who received semaglutide achieved an HbA_1c of 7.0% (53 mmol/mol) or less without weight gain or severe or blood-glucose–confirmed hypoglycemia (P less than .0001 vs. placebo).

Novo Nordisk funded the study. Three of the authors were employees of Novo Nordisk at the time of the study, and the remaining authors reported that they and/or their institutions had received funding from the company.

SOURCE: Zinman B et al. Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587(19)30066-X.

Black patients who undergo bariatric surgery have a higher rate of overall complications and a lower postsurgery quality of life than white patients, according to a study of bariatric surgery patients in Michigan.

“Per this analysis, there are significant racial disparities in perioperative outcomes, weight loss, and quality of life after bariatric surgery,” wrote lead author Michael H. Wood, MD, of Wayne State University, Detroit, and his coauthors, adding that, “while biological differences may explain some of the disparity in outcomes, environmental, social, and behavioral factors likely play a role.” The study was published online in JAMA Surgery.

This study reviewed data from 14,210 participants in the Michigan Bariatric Surgery Collaborative (MBSC), a state-wide consortium and clinical registry of bariatric surgery patients. Matching cohorts were established for black (n = 7,105) and white (n = 7,105) patients who underwent a primary bariatric operation (Roux-en-Y gastric bypass, sleeve gastrectomy, or adjustable gastric banding) between June 2006 and January 2017. The only significant differences between cohorts – clarified as “never more than 1 or 2 percentage points” – were in regard to income brackets and procedure type.

At 30-day follow-up, the rate of overall complications was higher in black patients (628, 8.8%) than in white patients (481, 6.8%; adjusted odds ratio, 1.33; 95% confidence interval, 1.17-1.51; P = .02), as was the length of stay (mean, 2.2 days vs. 1.9 days; aOR, 0.30; 95% CI, 0.20-0.40; P less than .001). Black patients also had a higher rate of both ED visits (541 [11.6%] vs. 826 [7.6%]; aOR, 1.60; 95% CI, 1.43-1.79; P less than .001) and readmissions (414 [5.8%] vs. 245 [3.5%]; aOR, 1.73; 95% CI, 1.47-2.03; P less than .001).

In addition, at 1-year follow-up, black patients had a lower mean weight loss (32.0 kg vs. 38.3 kg; P less than .001) and percentage of total weight loss (26% vs. 29%; P less than .001) compared with white patients. And though black patients were more likely than white patients to report a high quality of life before surgery (2,672 [49.5%] vs. 2,354 [41.4%]; P less than .001), they were less likely to do so 1 year afterward (1,379 [87.2%] vs. 2,133 [90.4%]; P = .002).

The coauthors acknowledged the limitations of their study, including potential unmeasured factors between cohorts such as disease duration or severity. They also noted that a wider time horizon than 30 days post surgery could have altered the results, although “serious adverse events and resource use tend to be highest within the first month after surgery, and we anticipate that this effect would have been negligible.”

The study was funded by Blue Cross Blue Shield Michigan/Blue Care Network. Dr. Wood reported no conflicts of interest. Three of his coauthors reported receiving salary support from Blue Cross Blue Shield Michigan/Blue Care Network for their work with the MBSC, and one other coauthor reported receiving an honorarium for being the MBSC’s executive committee chair.

SOURCE: Wood MH et al. JAMA Surg. 2019 Mar 6. doi: 10.1001/jamasurg.2019.0029.

Black patients who undergo bariatric surgery have a higher rate of overall complications and a lower postsurgery quality of life than white patients, according to a study of bariatric surgery patients in Michigan.

“Per this analysis, there are significant racial disparities in perioperative outcomes, weight loss, and quality of life after bariatric surgery,” wrote lead author Michael H. Wood, MD, of Wayne State University, Detroit, and his coauthors, adding that, “while biological differences may explain some of the disparity in outcomes, environmental, social, and behavioral factors likely play a role.” The study was published online in JAMA Surgery.

This study reviewed data from 14,210 participants in the Michigan Bariatric Surgery Collaborative (MBSC), a state-wide consortium and clinical registry of bariatric surgery patients. Matching cohorts were established for black (n = 7,105) and white (n = 7,105) patients who underwent a primary bariatric operation (Roux-en-Y gastric bypass, sleeve gastrectomy, or adjustable gastric banding) between June 2006 and January 2017. The only significant differences between cohorts – clarified as “never more than 1 or 2 percentage points” – were in regard to income brackets and procedure type.

At 30-day follow-up, the rate of overall complications was higher in black patients (628, 8.8%) than in white patients (481, 6.8%; adjusted odds ratio, 1.33; 95% confidence interval, 1.17-1.51; P = .02), as was the length of stay (mean, 2.2 days vs. 1.9 days; aOR, 0.30; 95% CI, 0.20-0.40; P less than .001). Black patients also had a higher rate of both ED visits (541 [11.6%] vs. 826 [7.6%]; aOR, 1.60; 95% CI, 1.43-1.79; P less than .001) and readmissions (414 [5.8%] vs. 245 [3.5%]; aOR, 1.73; 95% CI, 1.47-2.03; P less than .001).

In addition, at 1-year follow-up, black patients had a lower mean weight loss (32.0 kg vs. 38.3 kg; P less than .001) and percentage of total weight loss (26% vs. 29%; P less than .001) compared with white patients. And though black patients were more likely than white patients to report a high quality of life before surgery (2,672 [49.5%] vs. 2,354 [41.4%]; P less than .001), they were less likely to do so 1 year afterward (1,379 [87.2%] vs. 2,133 [90.4%]; P = .002).

The coauthors acknowledged the limitations of their study, including potential unmeasured factors between cohorts such as disease duration or severity. They also noted that a wider time horizon than 30 days post surgery could have altered the results, although “serious adverse events and resource use tend to be highest within the first month after surgery, and we anticipate that this effect would have been negligible.”

The study was funded by Blue Cross Blue Shield Michigan/Blue Care Network. Dr. Wood reported no conflicts of interest. Three of his coauthors reported receiving salary support from Blue Cross Blue Shield Michigan/Blue Care Network for their work with the MBSC, and one other coauthor reported receiving an honorarium for being the MBSC’s executive committee chair.

SOURCE: Wood MH et al. JAMA Surg. 2019 Mar 6. doi: 10.1001/jamasurg.2019.0029.

Black patients who undergo bariatric surgery have a higher rate of overall complications and a lower postsurgery quality of life than white patients, according to a study of bariatric surgery patients in Michigan.

“Per this analysis, there are significant racial disparities in perioperative outcomes, weight loss, and quality of life after bariatric surgery,” wrote lead author Michael H. Wood, MD, of Wayne State University, Detroit, and his coauthors, adding that, “while biological differences may explain some of the disparity in outcomes, environmental, social, and behavioral factors likely play a role.” The study was published online in JAMA Surgery.

This study reviewed data from 14,210 participants in the Michigan Bariatric Surgery Collaborative (MBSC), a state-wide consortium and clinical registry of bariatric surgery patients. Matching cohorts were established for black (n = 7,105) and white (n = 7,105) patients who underwent a primary bariatric operation (Roux-en-Y gastric bypass, sleeve gastrectomy, or adjustable gastric banding) between June 2006 and January 2017. The only significant differences between cohorts – clarified as “never more than 1 or 2 percentage points” – were in regard to income brackets and procedure type.

At 30-day follow-up, the rate of overall complications was higher in black patients (628, 8.8%) than in white patients (481, 6.8%; adjusted odds ratio, 1.33; 95% confidence interval, 1.17-1.51; P = .02), as was the length of stay (mean, 2.2 days vs. 1.9 days; aOR, 0.30; 95% CI, 0.20-0.40; P less than .001). Black patients also had a higher rate of both ED visits (541 [11.6%] vs. 826 [7.6%]; aOR, 1.60; 95% CI, 1.43-1.79; P less than .001) and readmissions (414 [5.8%] vs. 245 [3.5%]; aOR, 1.73; 95% CI, 1.47-2.03; P less than .001).

In addition, at 1-year follow-up, black patients had a lower mean weight loss (32.0 kg vs. 38.3 kg; P less than .001) and percentage of total weight loss (26% vs. 29%; P less than .001) compared with white patients. And though black patients were more likely than white patients to report a high quality of life before surgery (2,672 [49.5%] vs. 2,354 [41.4%]; P less than .001), they were less likely to do so 1 year afterward (1,379 [87.2%] vs. 2,133 [90.4%]; P = .002).

The coauthors acknowledged the limitations of their study, including potential unmeasured factors between cohorts such as disease duration or severity. They also noted that a wider time horizon than 30 days post surgery could have altered the results, although “serious adverse events and resource use tend to be highest within the first month after surgery, and we anticipate that this effect would have been negligible.”

The study was funded by Blue Cross Blue Shield Michigan/Blue Care Network. Dr. Wood reported no conflicts of interest. Three of his coauthors reported receiving salary support from Blue Cross Blue Shield Michigan/Blue Care Network for their work with the MBSC, and one other coauthor reported receiving an honorarium for being the MBSC’s executive committee chair.

SOURCE: Wood MH et al. JAMA Surg. 2019 Mar 6. doi: 10.1001/jamasurg.2019.0029.

LOS ANGELES – Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events in chronic and acute cardiovascular disease states in patients on maximally tolerated statins, according to the best available data.

Doug Brunk/MDedge News

In addition, there does not seem to be a floor of achieved LDL-C levels where cardiovascular outcomes are not decreased.

Those are two key lessons from recent trials of PCSK9 inhibitors that Norman E. Lepor, MD, highlighted at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. Anti-PCSK9 antibodies have shown a significant lipid-lowering effect, lowering LDL-C by 45%-55% from baseline regardless of whether patients are on statins or ezetimibe. More than 70% of high-risk patients are able to achieve an LDL-C level less than 70 mg/dL.

In two randomized trials known as SPIRE-1 and SPIRE-2, researchers compared the PCSK9 inhibitor bococizumab with placebo (N Engl J Med 2017;376:1527-39). The main difference between these two trials was the baseline cardiovascular risk was higher in SPIRE-2, particularly the baseline LDL levels. “Both trials were stopped early because of the increased incidence of antibodies against bococizumab as well as adverse events associated with that, particularly injection site reactions,” said Dr. Lepor, a cardiologist who is professor of medicine at the Geffen School of Medicine at UCLA.

SPIRE-1 did not show a significant difference within a short time of that trial, but SPIRE-2 showed a profound reduction in cardiovascular events within a short time. “That led to the conclusion that the higher the LDL, the higher risk you are, the more likely that you’re going to attain a more robust reduction of cardiovascular events,” Dr. Lepor said. Bococizumab, a partially humanized antibody, did not come to market because of the high incidence of anti-drug antibody and associated diminution of therapeutic effect, he added.

Next came the FOURIER trial of evolocumab, a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL or higher who were receiving statin therapy. Study participants received evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections (N Engl J Med. 2017;376:1713-22). “The reduction in LDL was very robust and occurred quite early, and there was consistency in terms of long-term effect,” said Dr. Lepor, a past president of the California chapter of the American College of Cardiology. Specifically, researchers observed a 15% reduction in the primary endpoints of a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (P less than .001), and a 20% reduction in the key secondary endpoints of a composite of cardiovascular death, MI, or stroke.

“It’s important to note that these are patients who were already well treated on statins,” he said. “There really does not seem to be a floor of LDL levels where we can say there is no further benefit. Achieved LDL-C at 4 weeks did lead to the ability to prognosticate benefit. We’re not seeing an increase in situations like diabetes, neurocognitive effects, and myalgias. The incidence of adverse events are similar to placebo. We feel very good that there do not seem to be safety issues for these agents, particularly in a population of patients with very low LDLs.” Dr. Lepor went on to note that FOURIER substudies have shown that there did not seem to be any increased incidence of neurocognitive disorders in patients taking evolocumab and that diabetes “tends to be a disease amplifier.”

In a more recent trial known as ODYSSEY OUTCOMES, 18,536 acute coronary syndrome (ACS) patients were randomized to alirocumab 75 mg once every 2 weeks or placebo (N Engl J Med. 2018;379:2097-107). The dose of alirocumab was increased to 150 mg every 2 weeks if the LDL was not lowered to less than 50 mg/dL. “The trial had other interesting aspects to it,” Dr. Lepor said. “If you had an LDL during the trial of less than 25 mg/dL, you were down-titrated from the 150-mg dose to the 75-mg dose, or if you were on the 75-mg dose with two consecutive LDLs less than 15 mg/dL, the alirocumab was stopped, all in blinded fashion.” The primary outcome was time to first occurrence of CHD death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina.

At baseline, patients had a median age of 58 years, 25% were women, their median LDL was 92 mg/dL. About 89% of patients were on high dose atorvastatin/rosuvastatin. Time from index ACS to randomization was a median of 2.6 months.

The primary efficacy endpoint was major adverse cardiac events including CHD death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. After a median follow-up of 2.8 years, the researchers observed highly significant 15% reduction of the primary endpoint with alirocumab compared with placebo (hazard ratio, 0.85; P = .0001), and a 15% reduction of death from any cause. In patients with a baseline LDL-C of 100 mg/dL or greater, the benefits of alirocumab were further amplified. “The higher your LDL, the higher your risk,” Dr. Lepor said. “The higher your risk, the greater your benefit from therapeutic intervention.”

He concluded his presentation by likening the treatment approach with PCSK9 inhibitors in ACS patients to that of chemotherapy in cancer patients. “In patients who have the very high risk of recurrence, those are the ones we want to attack with tougher chemotherapy,” he said. “Who are the patients who benefit most from PCSK9 inhibitors? ACS patients and those who are breaking through statin therapy with cardiovascular events, those with diabetes, CKD, and peripheral vascular disease.”

Dr. Lepor disclosed that he serves on the advisory board for Sanofi/Regeneron and is on the speakers bureau for Amgen and Sanofi/Regeneron.

[email protected]

LOS ANGELES – Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events in chronic and acute cardiovascular disease states in patients on maximally tolerated statins, according to the best available data.

Doug Brunk/MDedge News

In addition, there does not seem to be a floor of achieved LDL-C levels where cardiovascular outcomes are not decreased.

Those are two key lessons from recent trials of PCSK9 inhibitors that Norman E. Lepor, MD, highlighted at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. Anti-PCSK9 antibodies have shown a significant lipid-lowering effect, lowering LDL-C by 45%-55% from baseline regardless of whether patients are on statins or ezetimibe. More than 70% of high-risk patients are able to achieve an LDL-C level less than 70 mg/dL.

In two randomized trials known as SPIRE-1 and SPIRE-2, researchers compared the PCSK9 inhibitor bococizumab with placebo (N Engl J Med 2017;376:1527-39). The main difference between these two trials was the baseline cardiovascular risk was higher in SPIRE-2, particularly the baseline LDL levels. “Both trials were stopped early because of the increased incidence of antibodies against bococizumab as well as adverse events associated with that, particularly injection site reactions,” said Dr. Lepor, a cardiologist who is professor of medicine at the Geffen School of Medicine at UCLA.

SPIRE-1 did not show a significant difference within a short time of that trial, but SPIRE-2 showed a profound reduction in cardiovascular events within a short time. “That led to the conclusion that the higher the LDL, the higher risk you are, the more likely that you’re going to attain a more robust reduction of cardiovascular events,” Dr. Lepor said. Bococizumab, a partially humanized antibody, did not come to market because of the high incidence of anti-drug antibody and associated diminution of therapeutic effect, he added.

Next came the FOURIER trial of evolocumab, a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL or higher who were receiving statin therapy. Study participants received evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections (N Engl J Med. 2017;376:1713-22). “The reduction in LDL was very robust and occurred quite early, and there was consistency in terms of long-term effect,” said Dr. Lepor, a past president of the California chapter of the American College of Cardiology. Specifically, researchers observed a 15% reduction in the primary endpoints of a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (P less than .001), and a 20% reduction in the key secondary endpoints of a composite of cardiovascular death, MI, or stroke.

“It’s important to note that these are patients who were already well treated on statins,” he said. “There really does not seem to be a floor of LDL levels where we can say there is no further benefit. Achieved LDL-C at 4 weeks did lead to the ability to prognosticate benefit. We’re not seeing an increase in situations like diabetes, neurocognitive effects, and myalgias. The incidence of adverse events are similar to placebo. We feel very good that there do not seem to be safety issues for these agents, particularly in a population of patients with very low LDLs.” Dr. Lepor went on to note that FOURIER substudies have shown that there did not seem to be any increased incidence of neurocognitive disorders in patients taking evolocumab and that diabetes “tends to be a disease amplifier.”

In a more recent trial known as ODYSSEY OUTCOMES, 18,536 acute coronary syndrome (ACS) patients were randomized to alirocumab 75 mg once every 2 weeks or placebo (N Engl J Med. 2018;379:2097-107). The dose of alirocumab was increased to 150 mg every 2 weeks if the LDL was not lowered to less than 50 mg/dL. “The trial had other interesting aspects to it,” Dr. Lepor said. “If you had an LDL during the trial of less than 25 mg/dL, you were down-titrated from the 150-mg dose to the 75-mg dose, or if you were on the 75-mg dose with two consecutive LDLs less than 15 mg/dL, the alirocumab was stopped, all in blinded fashion.” The primary outcome was time to first occurrence of CHD death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina.

At baseline, patients had a median age of 58 years, 25% were women, their median LDL was 92 mg/dL. About 89% of patients were on high dose atorvastatin/rosuvastatin. Time from index ACS to randomization was a median of 2.6 months.

The primary efficacy endpoint was major adverse cardiac events including CHD death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. After a median follow-up of 2.8 years, the researchers observed highly significant 15% reduction of the primary endpoint with alirocumab compared with placebo (hazard ratio, 0.85; P = .0001), and a 15% reduction of death from any cause. In patients with a baseline LDL-C of 100 mg/dL or greater, the benefits of alirocumab were further amplified. “The higher your LDL, the higher your risk,” Dr. Lepor said. “The higher your risk, the greater your benefit from therapeutic intervention.”

He concluded his presentation by likening the treatment approach with PCSK9 inhibitors in ACS patients to that of chemotherapy in cancer patients. “In patients who have the very high risk of recurrence, those are the ones we want to attack with tougher chemotherapy,” he said. “Who are the patients who benefit most from PCSK9 inhibitors? ACS patients and those who are breaking through statin therapy with cardiovascular events, those with diabetes, CKD, and peripheral vascular disease.”

Dr. Lepor disclosed that he serves on the advisory board for Sanofi/Regeneron and is on the speakers bureau for Amgen and Sanofi/Regeneron.

[email protected]

LOS ANGELES – Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events in chronic and acute cardiovascular disease states in patients on maximally tolerated statins, according to the best available data.

Doug Brunk/MDedge News

In addition, there does not seem to be a floor of achieved LDL-C levels where cardiovascular outcomes are not decreased.

Those are two key lessons from recent trials of PCSK9 inhibitors that Norman E. Lepor, MD, highlighted at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. Anti-PCSK9 antibodies have shown a significant lipid-lowering effect, lowering LDL-C by 45%-55% from baseline regardless of whether patients are on statins or ezetimibe. More than 70% of high-risk patients are able to achieve an LDL-C level less than 70 mg/dL.

In two randomized trials known as SPIRE-1 and SPIRE-2, researchers compared the PCSK9 inhibitor bococizumab with placebo (N Engl J Med 2017;376:1527-39). The main difference between these two trials was the baseline cardiovascular risk was higher in SPIRE-2, particularly the baseline LDL levels. “Both trials were stopped early because of the increased incidence of antibodies against bococizumab as well as adverse events associated with that, particularly injection site reactions,” said Dr. Lepor, a cardiologist who is professor of medicine at the Geffen School of Medicine at UCLA.

SPIRE-1 did not show a significant difference within a short time of that trial, but SPIRE-2 showed a profound reduction in cardiovascular events within a short time. “That led to the conclusion that the higher the LDL, the higher risk you are, the more likely that you’re going to attain a more robust reduction of cardiovascular events,” Dr. Lepor said. Bococizumab, a partially humanized antibody, did not come to market because of the high incidence of anti-drug antibody and associated diminution of therapeutic effect, he added.

Next came the FOURIER trial of evolocumab, a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL or higher who were receiving statin therapy. Study participants received evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections (N Engl J Med. 2017;376:1713-22). “The reduction in LDL was very robust and occurred quite early, and there was consistency in terms of long-term effect,” said Dr. Lepor, a past president of the California chapter of the American College of Cardiology. Specifically, researchers observed a 15% reduction in the primary endpoints of a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (P less than .001), and a 20% reduction in the key secondary endpoints of a composite of cardiovascular death, MI, or stroke.

“It’s important to note that these are patients who were already well treated on statins,” he said. “There really does not seem to be a floor of LDL levels where we can say there is no further benefit. Achieved LDL-C at 4 weeks did lead to the ability to prognosticate benefit. We’re not seeing an increase in situations like diabetes, neurocognitive effects, and myalgias. The incidence of adverse events are similar to placebo. We feel very good that there do not seem to be safety issues for these agents, particularly in a population of patients with very low LDLs.” Dr. Lepor went on to note that FOURIER substudies have shown that there did not seem to be any increased incidence of neurocognitive disorders in patients taking evolocumab and that diabetes “tends to be a disease amplifier.”

In a more recent trial known as ODYSSEY OUTCOMES, 18,536 acute coronary syndrome (ACS) patients were randomized to alirocumab 75 mg once every 2 weeks or placebo (N Engl J Med. 2018;379:2097-107). The dose of alirocumab was increased to 150 mg every 2 weeks if the LDL was not lowered to less than 50 mg/dL. “The trial had other interesting aspects to it,” Dr. Lepor said. “If you had an LDL during the trial of less than 25 mg/dL, you were down-titrated from the 150-mg dose to the 75-mg dose, or if you were on the 75-mg dose with two consecutive LDLs less than 15 mg/dL, the alirocumab was stopped, all in blinded fashion.” The primary outcome was time to first occurrence of CHD death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina.

At baseline, patients had a median age of 58 years, 25% were women, their median LDL was 92 mg/dL. About 89% of patients were on high dose atorvastatin/rosuvastatin. Time from index ACS to randomization was a median of 2.6 months.

The primary efficacy endpoint was major adverse cardiac events including CHD death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. After a median follow-up of 2.8 years, the researchers observed highly significant 15% reduction of the primary endpoint with alirocumab compared with placebo (hazard ratio, 0.85; P = .0001), and a 15% reduction of death from any cause. In patients with a baseline LDL-C of 100 mg/dL or greater, the benefits of alirocumab were further amplified. “The higher your LDL, the higher your risk,” Dr. Lepor said. “The higher your risk, the greater your benefit from therapeutic intervention.”

He concluded his presentation by likening the treatment approach with PCSK9 inhibitors in ACS patients to that of chemotherapy in cancer patients. “In patients who have the very high risk of recurrence, those are the ones we want to attack with tougher chemotherapy,” he said. “Who are the patients who benefit most from PCSK9 inhibitors? ACS patients and those who are breaking through statin therapy with cardiovascular events, those with diabetes, CKD, and peripheral vascular disease.”

Dr. Lepor disclosed that he serves on the advisory board for Sanofi/Regeneron and is on the speakers bureau for Amgen and Sanofi/Regeneron.

[email protected]

Tourette syndrome and chronic tic disorder are associated with a “substantial risk” of metabolic and cardiovascular disorders such as obesity, type 2 diabetes mellitus (T2DM), and circulatory system diseases, according to a study published online Jan. 14 in JAMA Neurology.

The movement disorders are associated with cardiometabolic problems “even after taking into account a number of covariates and shared familial confounders and excluding relevant psychiatric comorbidities,” the researchers wrote. “The results highlight the importance of carefully monitoring cardiometabolic health in patients with Tourette syndrome or chronic tic disorder across the lifespan, particularly in those with comorbid attention-deficit/hyperactivity disorder (ADHD).”

Gustaf Brander, a researcher in the department of clinical neuroscience at Karolinska Institutet in Stockholm, and his colleagues conducted a longitudinal population-based cohort study of individuals living in Sweden between Jan. 1, 1973, and Dec. 31, 2013. The researchers assessed outcomes for patients with previously validated diagnoses of Tourette syndrome or chronic tic disorder in the Swedish National Patient Register. Main outcomes included obesity, dyslipidemia, hypertension, T2DM, and cardiovascular diseases, including ischemic heart diseases, arrhythmia, cerebrovascular diseases, transient ischemic attack, and arteriosclerosis. In addition, the researchers identified families with full siblings discordant for Tourette syndrome or chronic tic disorder.

Of the more than 14 million individuals in the cohort, 7,804 (76.4% male; median age at first diagnosis, 13.3 years) had a diagnosis of Tourette syndrome or chronic tic disorder in specialist care. Furthermore, the cohort included 5,141 families with full siblings who were discordant for these disorders.

Individuals with Tourette syndrome or chronic tic disorder had a higher risk for any metabolic or cardiovascular disorder, compared with the general population (hazard ratio adjusted by sex and birth year [aHR], 1.99) and sibling controls (aHR, 1.37). Specifically, individuals with Tourette syndrome or chronic tic disorder had higher risks for obesity (aHR, 2.76), T2DM(aHR, 1.67), and circulatory system diseases (aHR, 1.76).

The increased risk of any cardiometabolic disorder was significantly greater for males than it was for females (aHRs, 2.13 vs. 1.79), as was the risk of obesity (aHRs, 3.24 vs. 1.97).

The increased risk for cardiometabolic disorders in this patient population was evident by age 8 years. Exclusion of those patients with comorbid ADHD reduced but did not eliminate the risk (aHR, 1.52). The exclusion of other comorbidities did not significantly affect the results. Among patients with Tourette syndrome or chronic tic disorder, those who had received antipsychotic treatment for more than 1 year were significantly less likely to have metabolic and cardiovascular disorders, compared with patients not taking antipsychotic medication. This association may be related to “greater medical vigilance” and “should not be taken as evidence that antipsychotics are free from cardiometabolic adverse effects,” the authors noted.

The study was supported by a research grant from Tourettes Action. In addition, authors reported support from the Swedish Research Council and a Karolinska Institutet PhD stipend. Two authors disclosed personal fees from publishers, and one author disclosed grants and other funding from Shire.

[email protected]

SOURCE: Brander G et al. JAMA Neurol. 2019 Jan 14. doi: 10.1001/jamaneurol.2018.4279.

Tourette syndrome and chronic tic disorder are associated with a “substantial risk” of metabolic and cardiovascular disorders such as obesity, type 2 diabetes mellitus (T2DM), and circulatory system diseases, according to a study published online Jan. 14 in JAMA Neurology.

The movement disorders are associated with cardiometabolic problems “even after taking into account a number of covariates and shared familial confounders and excluding relevant psychiatric comorbidities,” the researchers wrote. “The results highlight the importance of carefully monitoring cardiometabolic health in patients with Tourette syndrome or chronic tic disorder across the lifespan, particularly in those with comorbid attention-deficit/hyperactivity disorder (ADHD).”

Gustaf Brander, a researcher in the department of clinical neuroscience at Karolinska Institutet in Stockholm, and his colleagues conducted a longitudinal population-based cohort study of individuals living in Sweden between Jan. 1, 1973, and Dec. 31, 2013. The researchers assessed outcomes for patients with previously validated diagnoses of Tourette syndrome or chronic tic disorder in the Swedish National Patient Register. Main outcomes included obesity, dyslipidemia, hypertension, T2DM, and cardiovascular diseases, including ischemic heart diseases, arrhythmia, cerebrovascular diseases, transient ischemic attack, and arteriosclerosis. In addition, the researchers identified families with full siblings discordant for Tourette syndrome or chronic tic disorder.

Of the more than 14 million individuals in the cohort, 7,804 (76.4% male; median age at first diagnosis, 13.3 years) had a diagnosis of Tourette syndrome or chronic tic disorder in specialist care. Furthermore, the cohort included 5,141 families with full siblings who were discordant for these disorders.

Individuals with Tourette syndrome or chronic tic disorder had a higher risk for any metabolic or cardiovascular disorder, compared with the general population (hazard ratio adjusted by sex and birth year [aHR], 1.99) and sibling controls (aHR, 1.37). Specifically, individuals with Tourette syndrome or chronic tic disorder had higher risks for obesity (aHR, 2.76), T2DM(aHR, 1.67), and circulatory system diseases (aHR, 1.76).

The increased risk of any cardiometabolic disorder was significantly greater for males than it was for females (aHRs, 2.13 vs. 1.79), as was the risk of obesity (aHRs, 3.24 vs. 1.97).

The increased risk for cardiometabolic disorders in this patient population was evident by age 8 years. Exclusion of those patients with comorbid ADHD reduced but did not eliminate the risk (aHR, 1.52). The exclusion of other comorbidities did not significantly affect the results. Among patients with Tourette syndrome or chronic tic disorder, those who had received antipsychotic treatment for more than 1 year were significantly less likely to have metabolic and cardiovascular disorders, compared with patients not taking antipsychotic medication. This association may be related to “greater medical vigilance” and “should not be taken as evidence that antipsychotics are free from cardiometabolic adverse effects,” the authors noted.

The study was supported by a research grant from Tourettes Action. In addition, authors reported support from the Swedish Research Council and a Karolinska Institutet PhD stipend. Two authors disclosed personal fees from publishers, and one author disclosed grants and other funding from Shire.

[email protected]

SOURCE: Brander G et al. JAMA Neurol. 2019 Jan 14. doi: 10.1001/jamaneurol.2018.4279.

Tourette syndrome and chronic tic disorder are associated with a “substantial risk” of metabolic and cardiovascular disorders such as obesity, type 2 diabetes mellitus (T2DM), and circulatory system diseases, according to a study published online Jan. 14 in JAMA Neurology.

The movement disorders are associated with cardiometabolic problems “even after taking into account a number of covariates and shared familial confounders and excluding relevant psychiatric comorbidities,” the researchers wrote. “The results highlight the importance of carefully monitoring cardiometabolic health in patients with Tourette syndrome or chronic tic disorder across the lifespan, particularly in those with comorbid attention-deficit/hyperactivity disorder (ADHD).”

Gustaf Brander, a researcher in the department of clinical neuroscience at Karolinska Institutet in Stockholm, and his colleagues conducted a longitudinal population-based cohort study of individuals living in Sweden between Jan. 1, 1973, and Dec. 31, 2013. The researchers assessed outcomes for patients with previously validated diagnoses of Tourette syndrome or chronic tic disorder in the Swedish National Patient Register. Main outcomes included obesity, dyslipidemia, hypertension, T2DM, and cardiovascular diseases, including ischemic heart diseases, arrhythmia, cerebrovascular diseases, transient ischemic attack, and arteriosclerosis. In addition, the researchers identified families with full siblings discordant for Tourette syndrome or chronic tic disorder.

Of the more than 14 million individuals in the cohort, 7,804 (76.4% male; median age at first diagnosis, 13.3 years) had a diagnosis of Tourette syndrome or chronic tic disorder in specialist care. Furthermore, the cohort included 5,141 families with full siblings who were discordant for these disorders.

Individuals with Tourette syndrome or chronic tic disorder had a higher risk for any metabolic or cardiovascular disorder, compared with the general population (hazard ratio adjusted by sex and birth year [aHR], 1.99) and sibling controls (aHR, 1.37). Specifically, individuals with Tourette syndrome or chronic tic disorder had higher risks for obesity (aHR, 2.76), T2DM(aHR, 1.67), and circulatory system diseases (aHR, 1.76).

The increased risk of any cardiometabolic disorder was significantly greater for males than it was for females (aHRs, 2.13 vs. 1.79), as was the risk of obesity (aHRs, 3.24 vs. 1.97).

The increased risk for cardiometabolic disorders in this patient population was evident by age 8 years. Exclusion of those patients with comorbid ADHD reduced but did not eliminate the risk (aHR, 1.52). The exclusion of other comorbidities did not significantly affect the results. Among patients with Tourette syndrome or chronic tic disorder, those who had received antipsychotic treatment for more than 1 year were significantly less likely to have metabolic and cardiovascular disorders, compared with patients not taking antipsychotic medication. This association may be related to “greater medical vigilance” and “should not be taken as evidence that antipsychotics are free from cardiometabolic adverse effects,” the authors noted.

The study was supported by a research grant from Tourettes Action. In addition, authors reported support from the Swedish Research Council and a Karolinska Institutet PhD stipend. Two authors disclosed personal fees from publishers, and one author disclosed grants and other funding from Shire.

[email protected]

SOURCE: Brander G et al. JAMA Neurol. 2019 Jan 14. doi: 10.1001/jamaneurol.2018.4279.

LOS ANGELES – Mounting evidence suggests that the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors helps prevent heart failure.

They also may play a role in the treatment of patients with known heart failure (HF), but further studies are required to prove definite treatment benefit.

“These trials enrolled a minority of patients with known heart failure, and, in those subgroups, the drugs seems to reduce the risk for hospitalization, opening the possibility of treatment benefit,” Javed Butler, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But there were not enough patients to conclude this. If you are treating diabetes with these agents in patients with heart failure, more power to you. But don’t think you are treating heart failure per se until the results of the dedicated heart failure trials come out.”

Good glycemic control has not been shown to affect heart failure outcomes per se, said Dr. Butler, professor and chairman of the department of medicine at the University of Mississippi Medical Center, Jackson.

“People seem to mix the concepts of prevention and treatment together,” he said. “We have now very good evidence across all trials with SGLT-2 inhibitors for prevention of heart failure. But for treatment, we need more data despite favorable early signals.

“Also, these trials include most patients with ischemic heart disease, but we don’t have data on nonischemic etiology for the development of heart failure from these trials,” Dr. Butler added.

The best available data from clinical trials suggest that patients with American College of Cardiology Foundation/American Heart Association heart failure classification stages A and B benefit the most from aggressive treatment to prevent HF.

“Either they have diseases like high blood pressure or diabetes, but their hearts are normal, or, perhaps, their hearts are abnormal, and they develop left ventricular hypertrophy or atrial fibrillation,” he said. “However, if someone is stage C – manifest heart failure – or stage D – advanced heart failure – we need further data on novel therapies to improve their outcomes.”

Dr. Butler emphasized that not all heart failure is associated with atherosclerotic vascular disease. In fact, the Health, Aging, and Body Composition Study showed that the incidence of heart failure increased progressively across age groups, both for those with and without a preceding vascular event (P = .03 and P less than .001, respectively; Eur J Heart Fail. 2014 May;16[5]:526-34). “There’s a whole other world of nonischemic heart failure that we also need to worry about,” he said. “There is a lot of microvascular endothelial dysfunction.”

The combination of heart failure and diabetes is especially lethal. “If you put them together, you’re looking at about a 10-fold higher risk of mortality, which is a horrible prognosis,” Dr. Butler said. “That means that we need to think about prevention and treatment separately.”

Data from the SAVOR-TIMI 53, EXAMINE, and TECOS trials show there is no protective effect of dipeptidyl peptidase–4 inhibitors when it comes to hospitalization for heart failure.

“The other classes of drugs either increase the risk, or we don’t have very good data,” Dr. Butler said. “So far, across the spectrum of therapies for diabetes, the effect on heart failure is neutral and perhaps confers some risk.”

SGLT-2 inhibitors convey a different story.

In the EMPA-REG OUTCOME Trial, one inclusion criterion was established cardiovascular disease (CVD) in the form of a prior MI, coronary artery disease, stroke, unstable angina, or occlusive peripheral artery disease, but not heart failure alone (N Engl J Med. 2015 Nov 26; 373[22]:2117-28). “This was not a heart failure study, so we don’t know what their New York Heart Association class was, or the details of their baseline HF treatment in the minority of patients who were enrolled who had a history of HF,” Dr. Butler cautioned.

However, the trial found that empagliflozin conferred an overall cardiovascular death risk reduction of 38%, compared with placebo. When the researchers assessed the impact of treatment on all modes of cardiovascular death, they found that death from heart failure benefited the most (hazard ratio, 0.32; P = .0008), while sudden death benefited as well. Empagliflozin also had a significant impact on reduced hospitalization for heart failure, compared with placebo (HR, 0.65).

“This is a large enough cohort that you should feel comfortable that this drug is preventing heart failure in those with HF at baseline,” said Dr. Butler, who was not involved with the study. “We can have a debate about whether this is a treatment for heart failure or not, but for prevention of heart failure, I feel comfortable that these drugs do that.”

A subsequent study of canagliflozin and cardiovascular and renal events in type 2 diabetes showed the same result (N Engl J Med. 2017 Aug 17; 377[7]:644-57). It reduced hospitalization for heart failure by 33% (HR, 0.67).

Then came the CVD-REAL study, which found low rates of hospitalization for heart failure and all-cause death in new users of SGLT-2 inhibitors. More recently, DECLARE-TIMI 58 yielded similar results.

“One of the criticisms of these findings is that heart failure characteristics were not well phenotyped in these studies,” Dr. Butler said. “I say it really does not matter. Heart failure hospitalizations are associated with a poor prognosis irrespective of whether the hospitalization occurred in patients without heart failure or in a patient with previously diagnosed heart failure, or whether the patient has reduced or preserved ejection fraction.

“Framingham and other classic studies show us that 5-year mortality for heart failure is about 50%,” he noted. “If you can prevent a disease that has a 5-year mortality of 50%, doesn’t that sound like a really good deal?”

A contemporary appraisal of the heart failure epidemic in Olmstead County, Minn., during 2000-2010 found that the mortality was 20.2% at 1 year after diagnosis, and 52.6% at 5 years after diagnosis. The data include new-onset HF in both inpatient and outpatient settings.

Specifically, new-onset HF hospitalization was associated with a 1-year post discharge mortality of 21.1% (JAMA Intern Med. 2015;175[6]:996-1004). “We cannot ignore prevention of heart failure,” Dr. Butler said. “Also, for treatment, once you get hospitalized for heart failure, the fundamental natural history of the disease changes. There is a 30% cumulative incremental death risk between the second and third hospitalizations.”

Dr. Butler concluded his presentation by noting that five randomized, controlled trials evaluating SGLT-2 inhibitors in HF have been launched, and should help elucidate any effects the drugs may have in treating the condition. They include EMPEROR-Preserved (NCT03057951), EMPEROR-Reduced (NCT03057977), Dapa-HF (NCT03036124), and SOLOIST-WHF (NCT03521934) and DELIVER (NCT03619213).

Dr. Butler disclosed that he has received research support from the National Institutes of Health, the European Union, and the Patient-Centered Outcomes Research Institute. He has also been a consultant for numerous pharmaceutical companies, including Boehringer Ingelheim, Janssen, and AstraZeneca, which sponsored the EMPA-REG, CANVAS, and DECLARE TIMI 58 trials.

[email protected]

LOS ANGELES – Mounting evidence suggests that the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors helps prevent heart failure.

They also may play a role in the treatment of patients with known heart failure (HF), but further studies are required to prove definite treatment benefit.

“These trials enrolled a minority of patients with known heart failure, and, in those subgroups, the drugs seems to reduce the risk for hospitalization, opening the possibility of treatment benefit,” Javed Butler, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But there were not enough patients to conclude this. If you are treating diabetes with these agents in patients with heart failure, more power to you. But don’t think you are treating heart failure per se until the results of the dedicated heart failure trials come out.”

Good glycemic control has not been shown to affect heart failure outcomes per se, said Dr. Butler, professor and chairman of the department of medicine at the University of Mississippi Medical Center, Jackson.

“People seem to mix the concepts of prevention and treatment together,” he said. “We have now very good evidence across all trials with SGLT-2 inhibitors for prevention of heart failure. But for treatment, we need more data despite favorable early signals.

“Also, these trials include most patients with ischemic heart disease, but we don’t have data on nonischemic etiology for the development of heart failure from these trials,” Dr. Butler added.

The best available data from clinical trials suggest that patients with American College of Cardiology Foundation/American Heart Association heart failure classification stages A and B benefit the most from aggressive treatment to prevent HF.

“Either they have diseases like high blood pressure or diabetes, but their hearts are normal, or, perhaps, their hearts are abnormal, and they develop left ventricular hypertrophy or atrial fibrillation,” he said. “However, if someone is stage C – manifest heart failure – or stage D – advanced heart failure – we need further data on novel therapies to improve their outcomes.”

Dr. Butler emphasized that not all heart failure is associated with atherosclerotic vascular disease. In fact, the Health, Aging, and Body Composition Study showed that the incidence of heart failure increased progressively across age groups, both for those with and without a preceding vascular event (P = .03 and P less than .001, respectively; Eur J Heart Fail. 2014 May;16[5]:526-34). “There’s a whole other world of nonischemic heart failure that we also need to worry about,” he said. “There is a lot of microvascular endothelial dysfunction.”

The combination of heart failure and diabetes is especially lethal. “If you put them together, you’re looking at about a 10-fold higher risk of mortality, which is a horrible prognosis,” Dr. Butler said. “That means that we need to think about prevention and treatment separately.”

Data from the SAVOR-TIMI 53, EXAMINE, and TECOS trials show there is no protective effect of dipeptidyl peptidase–4 inhibitors when it comes to hospitalization for heart failure.

“The other classes of drugs either increase the risk, or we don’t have very good data,” Dr. Butler said. “So far, across the spectrum of therapies for diabetes, the effect on heart failure is neutral and perhaps confers some risk.”

SGLT-2 inhibitors convey a different story.

In the EMPA-REG OUTCOME Trial, one inclusion criterion was established cardiovascular disease (CVD) in the form of a prior MI, coronary artery disease, stroke, unstable angina, or occlusive peripheral artery disease, but not heart failure alone (N Engl J Med. 2015 Nov 26; 373[22]:2117-28). “This was not a heart failure study, so we don’t know what their New York Heart Association class was, or the details of their baseline HF treatment in the minority of patients who were enrolled who had a history of HF,” Dr. Butler cautioned.

However, the trial found that empagliflozin conferred an overall cardiovascular death risk reduction of 38%, compared with placebo. When the researchers assessed the impact of treatment on all modes of cardiovascular death, they found that death from heart failure benefited the most (hazard ratio, 0.32; P = .0008), while sudden death benefited as well. Empagliflozin also had a significant impact on reduced hospitalization for heart failure, compared with placebo (HR, 0.65).

“This is a large enough cohort that you should feel comfortable that this drug is preventing heart failure in those with HF at baseline,” said Dr. Butler, who was not involved with the study. “We can have a debate about whether this is a treatment for heart failure or not, but for prevention of heart failure, I feel comfortable that these drugs do that.”

A subsequent study of canagliflozin and cardiovascular and renal events in type 2 diabetes showed the same result (N Engl J Med. 2017 Aug 17; 377[7]:644-57). It reduced hospitalization for heart failure by 33% (HR, 0.67).

Then came the CVD-REAL study, which found low rates of hospitalization for heart failure and all-cause death in new users of SGLT-2 inhibitors. More recently, DECLARE-TIMI 58 yielded similar results.

“One of the criticisms of these findings is that heart failure characteristics were not well phenotyped in these studies,” Dr. Butler said. “I say it really does not matter. Heart failure hospitalizations are associated with a poor prognosis irrespective of whether the hospitalization occurred in patients without heart failure or in a patient with previously diagnosed heart failure, or whether the patient has reduced or preserved ejection fraction.

“Framingham and other classic studies show us that 5-year mortality for heart failure is about 50%,” he noted. “If you can prevent a disease that has a 5-year mortality of 50%, doesn’t that sound like a really good deal?”

A contemporary appraisal of the heart failure epidemic in Olmstead County, Minn., during 2000-2010 found that the mortality was 20.2% at 1 year after diagnosis, and 52.6% at 5 years after diagnosis. The data include new-onset HF in both inpatient and outpatient settings.

Specifically, new-onset HF hospitalization was associated with a 1-year post discharge mortality of 21.1% (JAMA Intern Med. 2015;175[6]:996-1004). “We cannot ignore prevention of heart failure,” Dr. Butler said. “Also, for treatment, once you get hospitalized for heart failure, the fundamental natural history of the disease changes. There is a 30% cumulative incremental death risk between the second and third hospitalizations.”

Dr. Butler concluded his presentation by noting that five randomized, controlled trials evaluating SGLT-2 inhibitors in HF have been launched, and should help elucidate any effects the drugs may have in treating the condition. They include EMPEROR-Preserved (NCT03057951), EMPEROR-Reduced (NCT03057977), Dapa-HF (NCT03036124), and SOLOIST-WHF (NCT03521934) and DELIVER (NCT03619213).

Dr. Butler disclosed that he has received research support from the National Institutes of Health, the European Union, and the Patient-Centered Outcomes Research Institute. He has also been a consultant for numerous pharmaceutical companies, including Boehringer Ingelheim, Janssen, and AstraZeneca, which sponsored the EMPA-REG, CANVAS, and DECLARE TIMI 58 trials.

[email protected]

LOS ANGELES – Mounting evidence suggests that the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors helps prevent heart failure.

They also may play a role in the treatment of patients with known heart failure (HF), but further studies are required to prove definite treatment benefit.

“These trials enrolled a minority of patients with known heart failure, and, in those subgroups, the drugs seems to reduce the risk for hospitalization, opening the possibility of treatment benefit,” Javed Butler, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But there were not enough patients to conclude this. If you are treating diabetes with these agents in patients with heart failure, more power to you. But don’t think you are treating heart failure per se until the results of the dedicated heart failure trials come out.”

Good glycemic control has not been shown to affect heart failure outcomes per se, said Dr. Butler, professor and chairman of the department of medicine at the University of Mississippi Medical Center, Jackson.

“People seem to mix the concepts of prevention and treatment together,” he said. “We have now very good evidence across all trials with SGLT-2 inhibitors for prevention of heart failure. But for treatment, we need more data despite favorable early signals.

“Also, these trials include most patients with ischemic heart disease, but we don’t have data on nonischemic etiology for the development of heart failure from these trials,” Dr. Butler added.

The best available data from clinical trials suggest that patients with American College of Cardiology Foundation/American Heart Association heart failure classification stages A and B benefit the most from aggressive treatment to prevent HF.

“Either they have diseases like high blood pressure or diabetes, but their hearts are normal, or, perhaps, their hearts are abnormal, and they develop left ventricular hypertrophy or atrial fibrillation,” he said. “However, if someone is stage C – manifest heart failure – or stage D – advanced heart failure – we need further data on novel therapies to improve their outcomes.”

Dr. Butler emphasized that not all heart failure is associated with atherosclerotic vascular disease. In fact, the Health, Aging, and Body Composition Study showed that the incidence of heart failure increased progressively across age groups, both for those with and without a preceding vascular event (P = .03 and P less than .001, respectively; Eur J Heart Fail. 2014 May;16[5]:526-34). “There’s a whole other world of nonischemic heart failure that we also need to worry about,” he said. “There is a lot of microvascular endothelial dysfunction.”

The combination of heart failure and diabetes is especially lethal. “If you put them together, you’re looking at about a 10-fold higher risk of mortality, which is a horrible prognosis,” Dr. Butler said. “That means that we need to think about prevention and treatment separately.”

Data from the SAVOR-TIMI 53, EXAMINE, and TECOS trials show there is no protective effect of dipeptidyl peptidase–4 inhibitors when it comes to hospitalization for heart failure.

“The other classes of drugs either increase the risk, or we don’t have very good data,” Dr. Butler said. “So far, across the spectrum of therapies for diabetes, the effect on heart failure is neutral and perhaps confers some risk.”

SGLT-2 inhibitors convey a different story.

In the EMPA-REG OUTCOME Trial, one inclusion criterion was established cardiovascular disease (CVD) in the form of a prior MI, coronary artery disease, stroke, unstable angina, or occlusive peripheral artery disease, but not heart failure alone (N Engl J Med. 2015 Nov 26; 373[22]:2117-28). “This was not a heart failure study, so we don’t know what their New York Heart Association class was, or the details of their baseline HF treatment in the minority of patients who were enrolled who had a history of HF,” Dr. Butler cautioned.

However, the trial found that empagliflozin conferred an overall cardiovascular death risk reduction of 38%, compared with placebo. When the researchers assessed the impact of treatment on all modes of cardiovascular death, they found that death from heart failure benefited the most (hazard ratio, 0.32; P = .0008), while sudden death benefited as well. Empagliflozin also had a significant impact on reduced hospitalization for heart failure, compared with placebo (HR, 0.65).

“This is a large enough cohort that you should feel comfortable that this drug is preventing heart failure in those with HF at baseline,” said Dr. Butler, who was not involved with the study. “We can have a debate about whether this is a treatment for heart failure or not, but for prevention of heart failure, I feel comfortable that these drugs do that.”

A subsequent study of canagliflozin and cardiovascular and renal events in type 2 diabetes showed the same result (N Engl J Med. 2017 Aug 17; 377[7]:644-57). It reduced hospitalization for heart failure by 33% (HR, 0.67).

Then came the CVD-REAL study, which found low rates of hospitalization for heart failure and all-cause death in new users of SGLT-2 inhibitors. More recently, DECLARE-TIMI 58 yielded similar results.

“One of the criticisms of these findings is that heart failure characteristics were not well phenotyped in these studies,” Dr. Butler said. “I say it really does not matter. Heart failure hospitalizations are associated with a poor prognosis irrespective of whether the hospitalization occurred in patients without heart failure or in a patient with previously diagnosed heart failure, or whether the patient has reduced or preserved ejection fraction.

“Framingham and other classic studies show us that 5-year mortality for heart failure is about 50%,” he noted. “If you can prevent a disease that has a 5-year mortality of 50%, doesn’t that sound like a really good deal?”

A contemporary appraisal of the heart failure epidemic in Olmstead County, Minn., during 2000-2010 found that the mortality was 20.2% at 1 year after diagnosis, and 52.6% at 5 years after diagnosis. The data include new-onset HF in both inpatient and outpatient settings.

Specifically, new-onset HF hospitalization was associated with a 1-year post discharge mortality of 21.1% (JAMA Intern Med. 2015;175[6]:996-1004). “We cannot ignore prevention of heart failure,” Dr. Butler said. “Also, for treatment, once you get hospitalized for heart failure, the fundamental natural history of the disease changes. There is a 30% cumulative incremental death risk between the second and third hospitalizations.”

Dr. Butler concluded his presentation by noting that five randomized, controlled trials evaluating SGLT-2 inhibitors in HF have been launched, and should help elucidate any effects the drugs may have in treating the condition. They include EMPEROR-Preserved (NCT03057951), EMPEROR-Reduced (NCT03057977), Dapa-HF (NCT03036124), and SOLOIST-WHF (NCT03521934) and DELIVER (NCT03619213).

Dr. Butler disclosed that he has received research support from the National Institutes of Health, the European Union, and the Patient-Centered Outcomes Research Institute. He has also been a consultant for numerous pharmaceutical companies, including Boehringer Ingelheim, Janssen, and AstraZeneca, which sponsored the EMPA-REG, CANVAS, and DECLARE TIMI 58 trials.

[email protected]

LOS ANGELES – In some individuals, reduced degradation of insulin by the liver is the cause of type 2 diabetes mellitus.

Doug Brunk/MDedge News

That’s a hypothesis that Richard N. Bergman, PhD, and his colleagues are testing in his lab at the Sports Spectacular Diabetes and Obesity Wellness and Research Center at Cedars-Sinai Medical Center, Los Angeles.

“More than 50% of insulin secreted into the portal vein is degraded by the liver and never enters the systemic circulation,” Dr. Bergman said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “We have found that if you make an animal insulin resistant with a high fat diet, they degrade less of the insulin. Why is that? They deliver a higher fraction of the insulin into the systemic circulation. One of the answers is that the liver is a gateway for insulin delivery to the systemic circulation.” In fact, when he and his colleagues tested a population of normal dogs, they found wide variability in the ability of the liver to take up and degrade insulin (Diabetes. 2018 67[8]:1495-503).

“It ranged from 20% to 70%; I didn’t believe these data,” said Dr. Bergman, who is also chair in diabetes research at Cedars-Sinai. “We had to redo the study and the same thing was true. There’s a wide variation in what fraction of insulin that enters the liver is degraded. That led to the idea that this could be true in humans.”

[email protected]

LOS ANGELES – In some individuals, reduced degradation of insulin by the liver is the cause of type 2 diabetes mellitus.

Doug Brunk/MDedge News

That’s a hypothesis that Richard N. Bergman, PhD, and his colleagues are testing in his lab at the Sports Spectacular Diabetes and Obesity Wellness and Research Center at Cedars-Sinai Medical Center, Los Angeles.

“More than 50% of insulin secreted into the portal vein is degraded by the liver and never enters the systemic circulation,” Dr. Bergman said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “We have found that if you make an animal insulin resistant with a high fat diet, they degrade less of the insulin. Why is that? They deliver a higher fraction of the insulin into the systemic circulation. One of the answers is that the liver is a gateway for insulin delivery to the systemic circulation.” In fact, when he and his colleagues tested a population of normal dogs, they found wide variability in the ability of the liver to take up and degrade insulin (Diabetes. 2018 67[8]:1495-503).

“It ranged from 20% to 70%; I didn’t believe these data,” said Dr. Bergman, who is also chair in diabetes research at Cedars-Sinai. “We had to redo the study and the same thing was true. There’s a wide variation in what fraction of insulin that enters the liver is degraded. That led to the idea that this could be true in humans.”

[email protected]

LOS ANGELES – In some individuals, reduced degradation of insulin by the liver is the cause of type 2 diabetes mellitus.

Doug Brunk/MDedge News

That’s a hypothesis that Richard N. Bergman, PhD, and his colleagues are testing in his lab at the Sports Spectacular Diabetes and Obesity Wellness and Research Center at Cedars-Sinai Medical Center, Los Angeles.

“More than 50% of insulin secreted into the portal vein is degraded by the liver and never enters the systemic circulation,” Dr. Bergman said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “We have found that if you make an animal insulin resistant with a high fat diet, they degrade less of the insulin. Why is that? They deliver a higher fraction of the insulin into the systemic circulation. One of the answers is that the liver is a gateway for insulin delivery to the systemic circulation.” In fact, when he and his colleagues tested a population of normal dogs, they found wide variability in the ability of the liver to take up and degrade insulin (Diabetes. 2018 67[8]:1495-503).

“It ranged from 20% to 70%; I didn’t believe these data,” said Dr. Bergman, who is also chair in diabetes research at Cedars-Sinai. “We had to redo the study and the same thing was true. There’s a wide variation in what fraction of insulin that enters the liver is degraded. That led to the idea that this could be true in humans.”

[email protected]

LOS ANGELES – Mounting evidence indicates that obesity in childhood and adolescence increases the risk for future cardiovascular disease (CVD), according to Stephen R. Daniels, MD, PhD.

Doug Brunk/MDedge News

“Some of this increased risk is related to the high level of tracking of obesity from childhood to adolescence to adulthood,” Dr. Daniels, who chairs the department of pediatrics at the University of Colorado, Aurora, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But I think it’s also clear that childhood obesity is associated with risk factors for adult CVD, including hypertension, dyslipidemia, and type 2 diabetes. There’s a combination of things going on over the life course.”

Numerous studies have demonstrated a dose-response relationship between increased weight and all-cause mortality in cardiovascular disease for men and women. This operates through a variety of mechanisms, Dr. Daniels said, including hypertension, dyslipidemia, left ventricular hypertrophy, vascular inflammation, type 2 diabetes, and obstructive sleep apnea. “While overt cardiovascular disease does not occur in children, many of the mechanisms recognized in adults are also present in children and adolescents,” he said. “The trends for increasing prevalence and severity of obesity in children and the comorbid conditions associated with obesity are worrisome.”

The current prevalence of obesity in children and adolescents stands at about 18%, according to the latest National Health and Nutrition Examination Survey. However, the prevalence of severe obesity in youth aged 2-19 years has been increasing “fairly dramatically,” and now stands at 9% among girls and 8% among boys. Hispanics and non-Hispanic blacks are disproportionately affected. That may turn out to be important in terms of the future, Dr. Daniels said, because according to simulation models, childhood obesity and overweight will continue to be a major public health problem in the future (N Engl J Med. 2017;377:2145-53).


Direct evidence is also beginning to emerge of a link between obesity in youth and adult cardiovascular disease. The factors in childhood that predict adult obesity include a higher level of body mass index, obesity present at an older age (adolescence vs. childhood), and the presence of obesity in parents, which reflects both genes and environment. Researchers led by Paul W. Franks, PhD, evaluated 4,857 American Indian children without diabetes who were born between 1945 and 1984 and followed them for death before age 55 (N Engl J Med. 2010;362[6]:485-93). They assessed whether BMI, glucose tolerance, blood pressure, and cholesterol levels predicted premature death. There were 166 deaths from endogenous causes (3.4%) over a median follow-up of 24 years. Factors significantly associated with mortality included obesity (incident rate ratio 2.30), glucose tolerance (IRR 1.73), and hypertension (IRR 1.57).

In a separate analysis, researchers investigated the long-term effects of childhood weight on coronary heart disease (CHD) by studying 276,835 Danish schoolchildren for whom measurements of height and weight were available. They followed the individuals until they turned age 25 or older and used national registries to assess the fatal and nonfatal rates of CHD events (N Engl J Med. 2007;357:2329-37). The researchers found that higher BMI during childhood was associated with an increased risk of CVD in adulthood. However, they did not have data on BMI in adulthood, “which leaves open the question of whether childhood obesity works through adult obesity or also has an independent effect,” said Dr. Daniels, who is also pediatrician-in-chief at Children’s Hospital Colorado, Denver.

More recently, investigators studied 37,674 apparently healthy Israeli men from age 17 into adulthood (N Engl J Med. 2011;364:1315-25). Outcomes were coronary disease and diabetes. They found that an elevated BMI in adolescence is an independent risk factor for CVD in later life, while an elevated BMI in adulthood is an independent risk factor for both CVD and diabetes.

In the Fels Longitudinal Study, researchers enrolled 151 adults with metabolic syndrome and 154 without metabolic syndrome, with a mean age of 51 years (J Pediatr. 2008;152:191-200). “The idea was to look back at this cohort and see when the first differences might be observable between boys and girls who ultimately would develop metabolic syndrome and those who would not,” said Dr. Daniels, who was one of the study investigators. The first appearance of differences between adults with and without metabolic syndrome occurred at ages 8 and 13 for BMI and 6 and 13 for waist circumference in boys and girls, respectively. Odds ratios (ORs) for the metabolic syndrome in adulthood if BMI were elevated in childhood ranged from 1.4 to 1.9 in boys and from 0.8 to 2.8 in girls. At the same time, odds ratios for the metabolic syndrome in adulthood if waist circumference was elevated ranged from 2.5 to 31.4 in boys and 1.7 to 2.5 in girls.

“I think it’s safe to say that BMI and waist circumference may be important in predicting metabolic syndrome later in life and, ultimately, cardiovascular disease,” Dr. Daniels said.

He noted that as the prevalence and severity of obesity have increased in childhood, the prevalence of type 2 diabetes has also increased. “The time from diagnosis of diabetes to a CVD event is approximately 10-15 years in adults, and there is often a prediagnosis period of hyperglycemia, which ranges from 5-10 years,” Dr. Daniels said. “If the time course of CVD related to diabetes is the same for adolescents as adults, it is anticipated that adolescents with diabetes will begin having substantial CVD morbidity and mortality in their 30s or 40s. This will be a public health disaster. Emerging evidence from the TODAY study (Treatment Options for type 2 Diabetes in Adolescents and Youth) and other studies is emphasizing that at least some individuals with adolescent type 2 diabetes may have a more malignant form of disease than in adults. This is striking and important to consider as we look at how to prevent cardiovascular disease.”

Obesity in childhood is also associated with structural and functional abnormalities of the vasculature, according to studies that measure vascular structure via intima-media thickness of the carotid arteries, femoral arteries, abdominal aorta, or other arteries, as well as those that measure vascular stiffness via measures of intrinsic “visco-elastic” properties of the arterial wall. In one study of individuals aged 10-24 years, Dr. Daniels and his associates performed carotid ultrasound for carotid intima-media thickness on 182 patients who were lean, 136 who were obese, and 128 who had type 2 diabetes (Circulation 2009;119(22):2913-9). It demonstrated that youth with obesity and obesity-related type 2 diabetes have abnormalities in carotid thickness and stiffness that are only partially explained by traditional cardiovascular risk factors.

“We all know that obesity is very difficult to treat,” he concluded. “That’s true in children and adolescents as it is in adults. I think this argues for prevention of obesity, for us starting earlier, creating an optimal cardiovascular health situation that we can maintain during the course of childhood and adolescence. The payoff will be great if we can accomplish that.”

Dr. Daniels reported having no disclosures.

[email protected]

LOS ANGELES – Mounting evidence indicates that obesity in childhood and adolescence increases the risk for future cardiovascular disease (CVD), according to Stephen R. Daniels, MD, PhD.

Doug Brunk/MDedge News

“Some of this increased risk is related to the high level of tracking of obesity from childhood to adolescence to adulthood,” Dr. Daniels, who chairs the department of pediatrics at the University of Colorado, Aurora, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But I think it’s also clear that childhood obesity is associated with risk factors for adult CVD, including hypertension, dyslipidemia, and type 2 diabetes. There’s a combination of things going on over the life course.”

Numerous studies have demonstrated a dose-response relationship between increased weight and all-cause mortality in cardiovascular disease for men and women. This operates through a variety of mechanisms, Dr. Daniels said, including hypertension, dyslipidemia, left ventricular hypertrophy, vascular inflammation, type 2 diabetes, and obstructive sleep apnea. “While overt cardiovascular disease does not occur in children, many of the mechanisms recognized in adults are also present in children and adolescents,” he said. “The trends for increasing prevalence and severity of obesity in children and the comorbid conditions associated with obesity are worrisome.”

The current prevalence of obesity in children and adolescents stands at about 18%, according to the latest National Health and Nutrition Examination Survey. However, the prevalence of severe obesity in youth aged 2-19 years has been increasing “fairly dramatically,” and now stands at 9% among girls and 8% among boys. Hispanics and non-Hispanic blacks are disproportionately affected. That may turn out to be important in terms of the future, Dr. Daniels said, because according to simulation models, childhood obesity and overweight will continue to be a major public health problem in the future (N Engl J Med. 2017;377:2145-53).


Direct evidence is also beginning to emerge of a link between obesity in youth and adult cardiovascular disease. The factors in childhood that predict adult obesity include a higher level of body mass index, obesity present at an older age (adolescence vs. childhood), and the presence of obesity in parents, which reflects both genes and environment. Researchers led by Paul W. Franks, PhD, evaluated 4,857 American Indian children without diabetes who were born between 1945 and 1984 and followed them for death before age 55 (N Engl J Med. 2010;362[6]:485-93). They assessed whether BMI, glucose tolerance, blood pressure, and cholesterol levels predicted premature death. There were 166 deaths from endogenous causes (3.4%) over a median follow-up of 24 years. Factors significantly associated with mortality included obesity (incident rate ratio 2.30), glucose tolerance (IRR 1.73), and hypertension (IRR 1.57).

In a separate analysis, researchers investigated the long-term effects of childhood weight on coronary heart disease (CHD) by studying 276,835 Danish schoolchildren for whom measurements of height and weight were available. They followed the individuals until they turned age 25 or older and used national registries to assess the fatal and nonfatal rates of CHD events (N Engl J Med. 2007;357:2329-37). The researchers found that higher BMI during childhood was associated with an increased risk of CVD in adulthood. However, they did not have data on BMI in adulthood, “which leaves open the question of whether childhood obesity works through adult obesity or also has an independent effect,” said Dr. Daniels, who is also pediatrician-in-chief at Children’s Hospital Colorado, Denver.

More recently, investigators studied 37,674 apparently healthy Israeli men from age 17 into adulthood (N Engl J Med. 2011;364:1315-25). Outcomes were coronary disease and diabetes. They found that an elevated BMI in adolescence is an independent risk factor for CVD in later life, while an elevated BMI in adulthood is an independent risk factor for both CVD and diabetes.

In the Fels Longitudinal Study, researchers enrolled 151 adults with metabolic syndrome and 154 without metabolic syndrome, with a mean age of 51 years (J Pediatr. 2008;152:191-200). “The idea was to look back at this cohort and see when the first differences might be observable between boys and girls who ultimately would develop metabolic syndrome and those who would not,” said Dr. Daniels, who was one of the study investigators. The first appearance of differences between adults with and without metabolic syndrome occurred at ages 8 and 13 for BMI and 6 and 13 for waist circumference in boys and girls, respectively. Odds ratios (ORs) for the metabolic syndrome in adulthood if BMI were elevated in childhood ranged from 1.4 to 1.9 in boys and from 0.8 to 2.8 in girls. At the same time, odds ratios for the metabolic syndrome in adulthood if waist circumference was elevated ranged from 2.5 to 31.4 in boys and 1.7 to 2.5 in girls.

“I think it’s safe to say that BMI and waist circumference may be important in predicting metabolic syndrome later in life and, ultimately, cardiovascular disease,” Dr. Daniels said.

He noted that as the prevalence and severity of obesity have increased in childhood, the prevalence of type 2 diabetes has also increased. “The time from diagnosis of diabetes to a CVD event is approximately 10-15 years in adults, and there is often a prediagnosis period of hyperglycemia, which ranges from 5-10 years,” Dr. Daniels said. “If the time course of CVD related to diabetes is the same for adolescents as adults, it is anticipated that adolescents with diabetes will begin having substantial CVD morbidity and mortality in their 30s or 40s. This will be a public health disaster. Emerging evidence from the TODAY study (Treatment Options for type 2 Diabetes in Adolescents and Youth) and other studies is emphasizing that at least some individuals with adolescent type 2 diabetes may have a more malignant form of disease than in adults. This is striking and important to consider as we look at how to prevent cardiovascular disease.”

Obesity in childhood is also associated with structural and functional abnormalities of the vasculature, according to studies that measure vascular structure via intima-media thickness of the carotid arteries, femoral arteries, abdominal aorta, or other arteries, as well as those that measure vascular stiffness via measures of intrinsic “visco-elastic” properties of the arterial wall. In one study of individuals aged 10-24 years, Dr. Daniels and his associates performed carotid ultrasound for carotid intima-media thickness on 182 patients who were lean, 136 who were obese, and 128 who had type 2 diabetes (Circulation 2009;119(22):2913-9). It demonstrated that youth with obesity and obesity-related type 2 diabetes have abnormalities in carotid thickness and stiffness that are only partially explained by traditional cardiovascular risk factors.

“We all know that obesity is very difficult to treat,” he concluded. “That’s true in children and adolescents as it is in adults. I think this argues for prevention of obesity, for us starting earlier, creating an optimal cardiovascular health situation that we can maintain during the course of childhood and adolescence. The payoff will be great if we can accomplish that.”

Dr. Daniels reported having no disclosures.

[email protected]

LOS ANGELES – Mounting evidence indicates that obesity in childhood and adolescence increases the risk for future cardiovascular disease (CVD), according to Stephen R. Daniels, MD, PhD.

Doug Brunk/MDedge News

“Some of this increased risk is related to the high level of tracking of obesity from childhood to adolescence to adulthood,” Dr. Daniels, who chairs the department of pediatrics at the University of Colorado, Aurora, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But I think it’s also clear that childhood obesity is associated with risk factors for adult CVD, including hypertension, dyslipidemia, and type 2 diabetes. There’s a combination of things going on over the life course.”

Numerous studies have demonstrated a dose-response relationship between increased weight and all-cause mortality in cardiovascular disease for men and women. This operates through a variety of mechanisms, Dr. Daniels said, including hypertension, dyslipidemia, left ventricular hypertrophy, vascular inflammation, type 2 diabetes, and obstructive sleep apnea. “While overt cardiovascular disease does not occur in children, many of the mechanisms recognized in adults are also present in children and adolescents,” he said. “The trends for increasing prevalence and severity of obesity in children and the comorbid conditions associated with obesity are worrisome.”

The current prevalence of obesity in children and adolescents stands at about 18%, according to the latest National Health and Nutrition Examination Survey. However, the prevalence of severe obesity in youth aged 2-19 years has been increasing “fairly dramatically,” and now stands at 9% among girls and 8% among boys. Hispanics and non-Hispanic blacks are disproportionately affected. That may turn out to be important in terms of the future, Dr. Daniels said, because according to simulation models, childhood obesity and overweight will continue to be a major public health problem in the future (N Engl J Med. 2017;377:2145-53).


Direct evidence is also beginning to emerge of a link between obesity in youth and adult cardiovascular disease. The factors in childhood that predict adult obesity include a higher level of body mass index, obesity present at an older age (adolescence vs. childhood), and the presence of obesity in parents, which reflects both genes and environment. Researchers led by Paul W. Franks, PhD, evaluated 4,857 American Indian children without diabetes who were born between 1945 and 1984 and followed them for death before age 55 (N Engl J Med. 2010;362[6]:485-93). They assessed whether BMI, glucose tolerance, blood pressure, and cholesterol levels predicted premature death. There were 166 deaths from endogenous causes (3.4%) over a median follow-up of 24 years. Factors significantly associated with mortality included obesity (incident rate ratio 2.30), glucose tolerance (IRR 1.73), and hypertension (IRR 1.57).

In a separate analysis, researchers investigated the long-term effects of childhood weight on coronary heart disease (CHD) by studying 276,835 Danish schoolchildren for whom measurements of height and weight were available. They followed the individuals until they turned age 25 or older and used national registries to assess the fatal and nonfatal rates of CHD events (N Engl J Med. 2007;357:2329-37). The researchers found that higher BMI during childhood was associated with an increased risk of CVD in adulthood. However, they did not have data on BMI in adulthood, “which leaves open the question of whether childhood obesity works through adult obesity or also has an independent effect,” said Dr. Daniels, who is also pediatrician-in-chief at Children’s Hospital Colorado, Denver.

More recently, investigators studied 37,674 apparently healthy Israeli men from age 17 into adulthood (N Engl J Med. 2011;364:1315-25). Outcomes were coronary disease and diabetes. They found that an elevated BMI in adolescence is an independent risk factor for CVD in later life, while an elevated BMI in adulthood is an independent risk factor for both CVD and diabetes.

In the Fels Longitudinal Study, researchers enrolled 151 adults with metabolic syndrome and 154 without metabolic syndrome, with a mean age of 51 years (J Pediatr. 2008;152:191-200). “The idea was to look back at this cohort and see when the first differences might be observable between boys and girls who ultimately would develop metabolic syndrome and those who would not,” said Dr. Daniels, who was one of the study investigators. The first appearance of differences between adults with and without metabolic syndrome occurred at ages 8 and 13 for BMI and 6 and 13 for waist circumference in boys and girls, respectively. Odds ratios (ORs) for the metabolic syndrome in adulthood if BMI were elevated in childhood ranged from 1.4 to 1.9 in boys and from 0.8 to 2.8 in girls. At the same time, odds ratios for the metabolic syndrome in adulthood if waist circumference was elevated ranged from 2.5 to 31.4 in boys and 1.7 to 2.5 in girls.

“I think it’s safe to say that BMI and waist circumference may be important in predicting metabolic syndrome later in life and, ultimately, cardiovascular disease,” Dr. Daniels said.

He noted that as the prevalence and severity of obesity have increased in childhood, the prevalence of type 2 diabetes has also increased. “The time from diagnosis of diabetes to a CVD event is approximately 10-15 years in adults, and there is often a prediagnosis period of hyperglycemia, which ranges from 5-10 years,” Dr. Daniels said. “If the time course of CVD related to diabetes is the same for adolescents as adults, it is anticipated that adolescents with diabetes will begin having substantial CVD morbidity and mortality in their 30s or 40s. This will be a public health disaster. Emerging evidence from the TODAY study (Treatment Options for type 2 Diabetes in Adolescents and Youth) and other studies is emphasizing that at least some individuals with adolescent type 2 diabetes may have a more malignant form of disease than in adults. This is striking and important to consider as we look at how to prevent cardiovascular disease.”

Obesity in childhood is also associated with structural and functional abnormalities of the vasculature, according to studies that measure vascular structure via intima-media thickness of the carotid arteries, femoral arteries, abdominal aorta, or other arteries, as well as those that measure vascular stiffness via measures of intrinsic “visco-elastic” properties of the arterial wall. In one study of individuals aged 10-24 years, Dr. Daniels and his associates performed carotid ultrasound for carotid intima-media thickness on 182 patients who were lean, 136 who were obese, and 128 who had type 2 diabetes (Circulation 2009;119(22):2913-9). It demonstrated that youth with obesity and obesity-related type 2 diabetes have abnormalities in carotid thickness and stiffness that are only partially explained by traditional cardiovascular risk factors.

“We all know that obesity is very difficult to treat,” he concluded. “That’s true in children and adolescents as it is in adults. I think this argues for prevention of obesity, for us starting earlier, creating an optimal cardiovascular health situation that we can maintain during the course of childhood and adolescence. The payoff will be great if we can accomplish that.”

Dr. Daniels reported having no disclosures.

[email protected]

NASHVILLE, TENN. – Patients who took a fixed-dose combination of phentermine and topiramate–extended release (ER) lost over 15% of their body weight at 12 months, according to real-world experience from the Mayo Clinic in Rochester, Minn.

Kari Oakes/MDedge News

The results seen with the medication combo – a mean 15.5% total body weight loss at 12 months – bested the 8%-11% seen in randomized controlled trials (RCTs), said Gerardo Calderon, MD, in an interview during a poster session at Obesity Week, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery. The combination was also the most commonly prescribed weight loss medication at the Mayo Clinic, where Dr. Calderon is a gastroenterology and hepatology research fellow.

Patients taking lorcaserin at the Mayo Clinic also lost more weight loss than RCT participants (8.8% vs. 5%-6%, respectively). Notably, they also had a higher probability of losing at least 10% of their baseline total body weight (40% vs. 17%-23% in clinical trials). In RCTs, 37%-48% of patients taking phentermine/topiramate-ER had a total body weight loss of at least 10%, similar to the Mayo Clinic’s figure of 49%.

The rate of reported adverse events – 23.8% – exceeded that reported in RCTs, noted Dr. Calderon. Gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and constipation, were reported by 2%-20% of patients across the various drugs prescribed. Insomnia and mood changes, along with dizziness or lightheadedness, were reported by 2%-6% of patients. Almost 12% of patients taking phentermine/topiramate-SR reported paresthesias. No patients stopped taking their medication because of side effects, however.

The study was a review of patients seen at the Mayo Clinic during January 2016 – June 2018. Patients were included if they were prescribed weight loss medications and had a body mass index of at least 25 kg/m² with comorbidities related to adiposity or with a BMI of at least 30 without such comorbidities. To be included, patients had to be followed for at least 3 months and see a Mayo Clinic physician at least twice.

Patients with previous bariatric surgery or other major gastrointestinal surgery, those who didn’t use their medications because of insurance problems or drug costs, and those who were on weight loss medication before being seen for the first time were excluded from the study.

Patients were a mean 49 years old, and most were female (86/118; 72.9%). Mean BMI at enrollment was 41.7, with a mean weight of 117.6 kg.

Of 118 patients, 76 (64.4%) had dyslipidemia. About half of patients reported obstructive sleep apnea, and the same amount had hypertension. About 40% had diabetes, and the same number had degenerative joint disease.

Phentermine/topiramate was prescribed the most frequently, with 43.2% of patients on this medication. Liraglutide was taken by 34.7% of patients, bupropion/naltrexone-SR by 16.1%, and lorcaserin by 5.9%.

Patients taking liraglutide had similar weight loss (7.1%) to that seen in RCTs (6%-8%). For this medication, the real-world Mayo Clinic experience showed less chance of hitting the 10% total body weight loss mark (12% vs. 26%-33% in RCTs).

For bupropion/naltrexone-SR, weight loss was similar among the Mayo Clinic patients (7.2%) and RCT participants (5%-8%), and probability of achieving at least 10% total body weight loss was similar as well (32% vs. 34%).

Weight loss medication was a component of a multidisciplinary weight loss approach at Mayo Clinic. Physicians, dietitians, and psychologists worked together to care for patients with overweight and obesity at his facility, Dr. Calderon said. Overall, patients were followed for a mean 6.7 months, and patients had a mean 3 follow-up visits, with over half of patients attending at least one follow-up appointment in study months 6-12. At 12 months, though, the attrition rate was 57.9%. “We notice an attrition rate of almost 60% at 1 year. People are not coming to their follow-up. ... Definitely, this is something we are concerned about, and we would like to bring these attrition rates lower,” he said.

Most patients (63.6%) saw a dietitian, but on average, patients had just one appointment. “At the Mayo Clinic, we provide dietitians and psychological support. But it’s up to the patients if they want to have it or not,” said Dr. Calderon. “Most of them, they just went once to a dietitian.”

“Overall, these outcomes are similar to those in RCTs and support the concept that weight loss medications can achieve clinically significant weight loss in a multidisciplinary weight loss program,” noted Dr. Calderon and his coauthors.

Dr. Calderon reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Calderon G et al. Obesity Week, Abstract T-P-3425.

NASHVILLE, TENN. – Patients who took a fixed-dose combination of phentermine and topiramate–extended release (ER) lost over 15% of their body weight at 12 months, according to real-world experience from the Mayo Clinic in Rochester, Minn.

Kari Oakes/MDedge News

The results seen with the medication combo – a mean 15.5% total body weight loss at 12 months – bested the 8%-11% seen in randomized controlled trials (RCTs), said Gerardo Calderon, MD, in an interview during a poster session at Obesity Week, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery. The combination was also the most commonly prescribed weight loss medication at the Mayo Clinic, where Dr. Calderon is a gastroenterology and hepatology research fellow.

Patients taking lorcaserin at the Mayo Clinic also lost more weight loss than RCT participants (8.8% vs. 5%-6%, respectively). Notably, they also had a higher probability of losing at least 10% of their baseline total body weight (40% vs. 17%-23% in clinical trials). In RCTs, 37%-48% of patients taking phentermine/topiramate-ER had a total body weight loss of at least 10%, similar to the Mayo Clinic’s figure of 49%.

The rate of reported adverse events – 23.8% – exceeded that reported in RCTs, noted Dr. Calderon. Gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and constipation, were reported by 2%-20% of patients across the various drugs prescribed. Insomnia and mood changes, along with dizziness or lightheadedness, were reported by 2%-6% of patients. Almost 12% of patients taking phentermine/topiramate-SR reported paresthesias. No patients stopped taking their medication because of side effects, however.

The study was a review of patients seen at the Mayo Clinic during January 2016 – June 2018. Patients were included if they were prescribed weight loss medications and had a body mass index of at least 25 kg/m² with comorbidities related to adiposity or with a BMI of at least 30 without such comorbidities. To be included, patients had to be followed for at least 3 months and see a Mayo Clinic physician at least twice.

Patients with previous bariatric surgery or other major gastrointestinal surgery, those who didn’t use their medications because of insurance problems or drug costs, and those who were on weight loss medication before being seen for the first time were excluded from the study.

Patients were a mean 49 years old, and most were female (86/118; 72.9%). Mean BMI at enrollment was 41.7, with a mean weight of 117.6 kg.

Of 118 patients, 76 (64.4%) had dyslipidemia. About half of patients reported obstructive sleep apnea, and the same amount had hypertension. About 40% had diabetes, and the same number had degenerative joint disease.

Phentermine/topiramate was prescribed the most frequently, with 43.2% of patients on this medication. Liraglutide was taken by 34.7% of patients, bupropion/naltrexone-SR by 16.1%, and lorcaserin by 5.9%.

Patients taking liraglutide had similar weight loss (7.1%) to that seen in RCTs (6%-8%). For this medication, the real-world Mayo Clinic experience showed less chance of hitting the 10% total body weight loss mark (12% vs. 26%-33% in RCTs).

For bupropion/naltrexone-SR, weight loss was similar among the Mayo Clinic patients (7.2%) and RCT participants (5%-8%), and probability of achieving at least 10% total body weight loss was similar as well (32% vs. 34%).

Weight loss medication was a component of a multidisciplinary weight loss approach at Mayo Clinic. Physicians, dietitians, and psychologists worked together to care for patients with overweight and obesity at his facility, Dr. Calderon said. Overall, patients were followed for a mean 6.7 months, and patients had a mean 3 follow-up visits, with over half of patients attending at least one follow-up appointment in study months 6-12. At 12 months, though, the attrition rate was 57.9%. “We notice an attrition rate of almost 60% at 1 year. People are not coming to their follow-up. ... Definitely, this is something we are concerned about, and we would like to bring these attrition rates lower,” he said.

Most patients (63.6%) saw a dietitian, but on average, patients had just one appointment. “At the Mayo Clinic, we provide dietitians and psychological support. But it’s up to the patients if they want to have it or not,” said Dr. Calderon. “Most of them, they just went once to a dietitian.”

“Overall, these outcomes are similar to those in RCTs and support the concept that weight loss medications can achieve clinically significant weight loss in a multidisciplinary weight loss program,” noted Dr. Calderon and his coauthors.

Dr. Calderon reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Calderon G et al. Obesity Week, Abstract T-P-3425.

NASHVILLE, TENN. – Patients who took a fixed-dose combination of phentermine and topiramate–extended release (ER) lost over 15% of their body weight at 12 months, according to real-world experience from the Mayo Clinic in Rochester, Minn.

Kari Oakes/MDedge News

The results seen with the medication combo – a mean 15.5% total body weight loss at 12 months – bested the 8%-11% seen in randomized controlled trials (RCTs), said Gerardo Calderon, MD, in an interview during a poster session at Obesity Week, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery. The combination was also the most commonly prescribed weight loss medication at the Mayo Clinic, where Dr. Calderon is a gastroenterology and hepatology research fellow.

Patients taking lorcaserin at the Mayo Clinic also lost more weight loss than RCT participants (8.8% vs. 5%-6%, respectively). Notably, they also had a higher probability of losing at least 10% of their baseline total body weight (40% vs. 17%-23% in clinical trials). In RCTs, 37%-48% of patients taking phentermine/topiramate-ER had a total body weight loss of at least 10%, similar to the Mayo Clinic’s figure of 49%.

The rate of reported adverse events – 23.8% – exceeded that reported in RCTs, noted Dr. Calderon. Gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and constipation, were reported by 2%-20% of patients across the various drugs prescribed. Insomnia and mood changes, along with dizziness or lightheadedness, were reported by 2%-6% of patients. Almost 12% of patients taking phentermine/topiramate-SR reported paresthesias. No patients stopped taking their medication because of side effects, however.

The study was a review of patients seen at the Mayo Clinic during January 2016 – June 2018. Patients were included if they were prescribed weight loss medications and had a body mass index of at least 25 kg/m² with comorbidities related to adiposity or with a BMI of at least 30 without such comorbidities. To be included, patients had to be followed for at least 3 months and see a Mayo Clinic physician at least twice.

Patients with previous bariatric surgery or other major gastrointestinal surgery, those who didn’t use their medications because of insurance problems or drug costs, and those who were on weight loss medication before being seen for the first time were excluded from the study.

Patients were a mean 49 years old, and most were female (86/118; 72.9%). Mean BMI at enrollment was 41.7, with a mean weight of 117.6 kg.

Of 118 patients, 76 (64.4%) had dyslipidemia. About half of patients reported obstructive sleep apnea, and the same amount had hypertension. About 40% had diabetes, and the same number had degenerative joint disease.

Phentermine/topiramate was prescribed the most frequently, with 43.2% of patients on this medication. Liraglutide was taken by 34.7% of patients, bupropion/naltrexone-SR by 16.1%, and lorcaserin by 5.9%.

Patients taking liraglutide had similar weight loss (7.1%) to that seen in RCTs (6%-8%). For this medication, the real-world Mayo Clinic experience showed less chance of hitting the 10% total body weight loss mark (12% vs. 26%-33% in RCTs).

For bupropion/naltrexone-SR, weight loss was similar among the Mayo Clinic patients (7.2%) and RCT participants (5%-8%), and probability of achieving at least 10% total body weight loss was similar as well (32% vs. 34%).

Weight loss medication was a component of a multidisciplinary weight loss approach at Mayo Clinic. Physicians, dietitians, and psychologists worked together to care for patients with overweight and obesity at his facility, Dr. Calderon said. Overall, patients were followed for a mean 6.7 months, and patients had a mean 3 follow-up visits, with over half of patients attending at least one follow-up appointment in study months 6-12. At 12 months, though, the attrition rate was 57.9%. “We notice an attrition rate of almost 60% at 1 year. People are not coming to their follow-up. ... Definitely, this is something we are concerned about, and we would like to bring these attrition rates lower,” he said.

Most patients (63.6%) saw a dietitian, but on average, patients had just one appointment. “At the Mayo Clinic, we provide dietitians and psychological support. But it’s up to the patients if they want to have it or not,” said Dr. Calderon. “Most of them, they just went once to a dietitian.”

“Overall, these outcomes are similar to those in RCTs and support the concept that weight loss medications can achieve clinically significant weight loss in a multidisciplinary weight loss program,” noted Dr. Calderon and his coauthors.

Dr. Calderon reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Calderon G et al. Obesity Week, Abstract T-P-3425.