Diabetes Hub

NASHVILLE – Saroglitazar, currently approved for use in India only, is effective and safe for treating diabetic dyslipidemia and has been shown to be a potent agent for managing levels of triglycerides, cholesterol, glucose, and hemoglobin A_1c.

This is according to a postmarketing surveillance study presented by Dr. Shashank Joshi, whose endocrinology clinic in Mumbai was involved in a 9-month trial to test the safety and efficacy of once-daily 4-mg doses of Saroglitazar on a population with diabetic dyslipidemia. Saroglitazar, manufactured by Zydus, is the first dual-PPAR (peroxisome proliferator-activated receptor) alpha and gamma agonist available commercially anywhere in the world, and has been approved only in India and on the market in that country for 20 months.

“[Saroglitazar] is fundamentally not structurally similar to a glitazone, [nor] to a fibrate, and it’s also not structurally similar to other glitazars, which have been investigated,” explained Dr. Joshi, who added that all phase III studies of saroglitazar have been published. “We [also] know diabetic dyslipidemia is very prevalent in the Indian population, shown predominantly [by] low HDL, high triglycerides, and high LDL.”

A total of 787 diabetic dyslipidemia patients were included in the study, all of whom were evaluated for lipid and glycemic parameters at baseline. The mean age of subjects was 53 years, mean weight was 73.9 kg, and 507 subjects (64.4%) were male. All subjects underwent follow-ups at 3, 6, and 9 months after baseline.

Mean triglyceride, LDL cholesterol, non-HDL cholesterol, and total cholesterol levels all showed significant reductions: Triglycerides dropped 43.8% from 297.9 mg/dL to 156.1 mg/dL, LDL levels dropped 18.5% from 132.5 mg/dL to 100.5 mg/dL, non-HDL levels dropped 29.7% from 199 mg/dL to 131.9 mg/dL, and total cholesterol levels dropped 23.1% from 239.9 mg/dL to 176.6 mg/dL (P <.001 for all).

Significant reductions were also seen in HbA_1clevels (8.5% to 7%), fasting glucose levels (171.6 mg/dL to 116.4 mg/dL), and postprandial glucose levels (244.6 mg/dL to 149.7 mg/dL) (P <.001 for all). Furthermore, HDL levels improved by 12.7%, over the 9-month period, going from 41 mg/dL to 44.5 mg/dL.

Seven hundred and twenty-two subjects (91.7%) were on an antidiabetic medication at baseline, the most common of which were metformin (73.7%), sulfonylureas (58.3%), dipeptidyl peptidase–4 inhibitors (26.2%), and insulin (17.4%). More than half of these patients (365; 50.6%) were on dual therapy, 195 (27%) were on triple therapy, 135 (18.7%) were on monotherapy, and 27 (3.7%) of these subjects were taking more than three drugs at baseline. Of the 787 in the total population, 395 (50.2%) were on statins, the most common of which was atorvastatin (71%).

“[Saroglitazar] was well tolerated over a long term of 9 months, with no weight gain and edema, and no serious adverse events reported,” said Dr. Joshi, who also acknowledged potential limitations of the trial because of its being an ongoing, prospective study.

Dr. Joshi disclosed relationships with Zydus, maker of saroglitazar, and numerous other pharmaceutical companies.

[email protected]

NASHVILLE – Saroglitazar, currently approved for use in India only, is effective and safe for treating diabetic dyslipidemia and has been shown to be a potent agent for managing levels of triglycerides, cholesterol, glucose, and hemoglobin A_1c.

This is according to a postmarketing surveillance study presented by Dr. Shashank Joshi, whose endocrinology clinic in Mumbai was involved in a 9-month trial to test the safety and efficacy of once-daily 4-mg doses of Saroglitazar on a population with diabetic dyslipidemia. Saroglitazar, manufactured by Zydus, is the first dual-PPAR (peroxisome proliferator-activated receptor) alpha and gamma agonist available commercially anywhere in the world, and has been approved only in India and on the market in that country for 20 months.

“[Saroglitazar] is fundamentally not structurally similar to a glitazone, [nor] to a fibrate, and it’s also not structurally similar to other glitazars, which have been investigated,” explained Dr. Joshi, who added that all phase III studies of saroglitazar have been published. “We [also] know diabetic dyslipidemia is very prevalent in the Indian population, shown predominantly [by] low HDL, high triglycerides, and high LDL.”

A total of 787 diabetic dyslipidemia patients were included in the study, all of whom were evaluated for lipid and glycemic parameters at baseline. The mean age of subjects was 53 years, mean weight was 73.9 kg, and 507 subjects (64.4%) were male. All subjects underwent follow-ups at 3, 6, and 9 months after baseline.

Mean triglyceride, LDL cholesterol, non-HDL cholesterol, and total cholesterol levels all showed significant reductions: Triglycerides dropped 43.8% from 297.9 mg/dL to 156.1 mg/dL, LDL levels dropped 18.5% from 132.5 mg/dL to 100.5 mg/dL, non-HDL levels dropped 29.7% from 199 mg/dL to 131.9 mg/dL, and total cholesterol levels dropped 23.1% from 239.9 mg/dL to 176.6 mg/dL (P <.001 for all).

Significant reductions were also seen in HbA_1clevels (8.5% to 7%), fasting glucose levels (171.6 mg/dL to 116.4 mg/dL), and postprandial glucose levels (244.6 mg/dL to 149.7 mg/dL) (P <.001 for all). Furthermore, HDL levels improved by 12.7%, over the 9-month period, going from 41 mg/dL to 44.5 mg/dL.

Seven hundred and twenty-two subjects (91.7%) were on an antidiabetic medication at baseline, the most common of which were metformin (73.7%), sulfonylureas (58.3%), dipeptidyl peptidase–4 inhibitors (26.2%), and insulin (17.4%). More than half of these patients (365; 50.6%) were on dual therapy, 195 (27%) were on triple therapy, 135 (18.7%) were on monotherapy, and 27 (3.7%) of these subjects were taking more than three drugs at baseline. Of the 787 in the total population, 395 (50.2%) were on statins, the most common of which was atorvastatin (71%).

“[Saroglitazar] was well tolerated over a long term of 9 months, with no weight gain and edema, and no serious adverse events reported,” said Dr. Joshi, who also acknowledged potential limitations of the trial because of its being an ongoing, prospective study.

Dr. Joshi disclosed relationships with Zydus, maker of saroglitazar, and numerous other pharmaceutical companies.

[email protected]

NASHVILLE – Saroglitazar, currently approved for use in India only, is effective and safe for treating diabetic dyslipidemia and has been shown to be a potent agent for managing levels of triglycerides, cholesterol, glucose, and hemoglobin A_1c.

This is according to a postmarketing surveillance study presented by Dr. Shashank Joshi, whose endocrinology clinic in Mumbai was involved in a 9-month trial to test the safety and efficacy of once-daily 4-mg doses of Saroglitazar on a population with diabetic dyslipidemia. Saroglitazar, manufactured by Zydus, is the first dual-PPAR (peroxisome proliferator-activated receptor) alpha and gamma agonist available commercially anywhere in the world, and has been approved only in India and on the market in that country for 20 months.

“[Saroglitazar] is fundamentally not structurally similar to a glitazone, [nor] to a fibrate, and it’s also not structurally similar to other glitazars, which have been investigated,” explained Dr. Joshi, who added that all phase III studies of saroglitazar have been published. “We [also] know diabetic dyslipidemia is very prevalent in the Indian population, shown predominantly [by] low HDL, high triglycerides, and high LDL.”

A total of 787 diabetic dyslipidemia patients were included in the study, all of whom were evaluated for lipid and glycemic parameters at baseline. The mean age of subjects was 53 years, mean weight was 73.9 kg, and 507 subjects (64.4%) were male. All subjects underwent follow-ups at 3, 6, and 9 months after baseline.

Mean triglyceride, LDL cholesterol, non-HDL cholesterol, and total cholesterol levels all showed significant reductions: Triglycerides dropped 43.8% from 297.9 mg/dL to 156.1 mg/dL, LDL levels dropped 18.5% from 132.5 mg/dL to 100.5 mg/dL, non-HDL levels dropped 29.7% from 199 mg/dL to 131.9 mg/dL, and total cholesterol levels dropped 23.1% from 239.9 mg/dL to 176.6 mg/dL (P <.001 for all).

Significant reductions were also seen in HbA_1clevels (8.5% to 7%), fasting glucose levels (171.6 mg/dL to 116.4 mg/dL), and postprandial glucose levels (244.6 mg/dL to 149.7 mg/dL) (P <.001 for all). Furthermore, HDL levels improved by 12.7%, over the 9-month period, going from 41 mg/dL to 44.5 mg/dL.

Seven hundred and twenty-two subjects (91.7%) were on an antidiabetic medication at baseline, the most common of which were metformin (73.7%), sulfonylureas (58.3%), dipeptidyl peptidase–4 inhibitors (26.2%), and insulin (17.4%). More than half of these patients (365; 50.6%) were on dual therapy, 195 (27%) were on triple therapy, 135 (18.7%) were on monotherapy, and 27 (3.7%) of these subjects were taking more than three drugs at baseline. Of the 787 in the total population, 395 (50.2%) were on statins, the most common of which was atorvastatin (71%).

“[Saroglitazar] was well tolerated over a long term of 9 months, with no weight gain and edema, and no serious adverse events reported,” said Dr. Joshi, who also acknowledged potential limitations of the trial because of its being an ongoing, prospective study.

Dr. Joshi disclosed relationships with Zydus, maker of saroglitazar, and numerous other pharmaceutical companies.

[email protected]

GAITHERSBURG, MD. – The majority of a Food and Drug Administration Advisory panel has supported the approval of alirocumab, a biologic lipid-lowering drug injected subcutaneously twice a month, as a long-term treatment for hypercholesterolemia, but support for the different patient populations included in the proposed indication varied.

At a meeting on June 9, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-3 that the manufacturer had “sufficiently established that the LDL cholesterol–lowering benefit of alirocumab exceeds its risks,” and to “support approval in one or more patient populations,” the question posed to the panel. However, those voting in favor of approval said the optimal benefit would be in patients with familial hypercholesterolemia; there was also support among some panelists for patients who are truly statin intolerant and those who cannot get to goal on statin therapy alone and are at a high cardiovascular risk.

Elizabeth Mechcatie/Frontline Medical News

The proposed indication for the PCSK9-inhibitor is for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes, to reduce LDL cholesterol, total cholesterol, non-HDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein A, and to increase HDL cholesterol and apolipoprotein A-1 (Apo A-1) – either in combination with a statin or as monotherapy, including in patients who cannot tolerate statins. The proposed dose is 75 mg administered subcutaneously every 2 weeks (or a starting dose of 150 mg every 2 weeks for patients who need more than a 60% reduction in LDL-C.

Dr. Brendan Everett, director of the cardiology inpatient service at Brigham and Women’s Hospital, Boston, voted for approval, because of the drug’s potential benefits for patients with heterozygous FH, but added that he would restrict approval to these patients, and did not support approval in other patients, such as those with mixed dyslipidemia.

Alirocumab was compared with placebo or ezetimibe in 10 phase III studies of about 5,100 patients, including those at high CV risk and statin-intolerant patients.

The percent reduction in LDL cholesterol at 24 weeks, from baseline, was the primary endpoint. Summarizing the FDA’s view on the safety and efficacy of alirocumab, Dr. Julie Golden, a medical reviewer in the FDA’s division of metabolism and endocrinology products, said that the agency agrees with the manufacturer, that alirocumab is associated with “substantial and persistent” cholesterol-lowering effects, compared with controls, in all patient populations studied. However, any conclusions about CV benefits are “premature,” she said.

Panelists said that in the studies, there were “weak” safety signals for neurocognitive effects, diabetes, and abnormal liver enzymes, but they were somewhat reassured by the absence of any “highly concerning” adverse events in the studies. Panelists said there was little or no evidence that very low levels of LDL cholesterol are harmful, but that did not provide assurance of safety of very low levels. Several panelists raised the concern that statins may be reduced or stopped in patients whose LDL cholesterol levels dropped to very low levels while on alirocumab, instead of stopping treatment with alirocumab.

Over 20 years, the FDA has accepted reductions in LDL cholesterol as a surrogate for CV risk reduction to support approval of lipid-lowering drugs, but once approved, CV outcomes trials are not required. One of the panelists voting against approval was Dr. Peter Wilson, professor of medicine and public health, Emory University, who said that cardiovascular outcomes data were needed to support approval. “I no longer think we are in an LDL-surrogate era,” he noted.

The alirocumab CV outcomes study – the ODYSSEY Outcomes trial – is enrolling 18,000 patients with recent acute coronary syndrome who are on high intensity statin treatment and are randomized to alirocumab or placebo; MACE is the primary endpoint. The company expects that enrollment in the outcomes study will be completed this year and results will be available in 2017; it will represent 50,000 patient years of experience (vs. 5,000 patient years with the phase III trials) and will include further evaluation of the risks associated with treatment.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists had no potential conflicts of interest.

If approved, Sanofi and Regeneron plan to market alirocumab as Praluent; a decision is expected by July 24th.

On June 10, the panel will review evolocumab, another PCSK9-inhibitor. If approved, these will be the first drugs in this new class of lipid-lowering agents to be approved in the United States. They are human monoclonal antibodies that bind to proprotein convertase subtilisin kexin type 9 (PCSK9), a serine protease that is involved in the regulation of LDL receptor (LDR-R). Inactivation of PCSK9 results in an increase of LDL-R available to clear LDL-C, reducing LDL-C levels.

[email protected]

GAITHERSBURG, MD. – The majority of a Food and Drug Administration Advisory panel has supported the approval of alirocumab, a biologic lipid-lowering drug injected subcutaneously twice a month, as a long-term treatment for hypercholesterolemia, but support for the different patient populations included in the proposed indication varied.

At a meeting on June 9, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-3 that the manufacturer had “sufficiently established that the LDL cholesterol–lowering benefit of alirocumab exceeds its risks,” and to “support approval in one or more patient populations,” the question posed to the panel. However, those voting in favor of approval said the optimal benefit would be in patients with familial hypercholesterolemia; there was also support among some panelists for patients who are truly statin intolerant and those who cannot get to goal on statin therapy alone and are at a high cardiovascular risk.

Elizabeth Mechcatie/Frontline Medical News

The proposed indication for the PCSK9-inhibitor is for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes, to reduce LDL cholesterol, total cholesterol, non-HDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein A, and to increase HDL cholesterol and apolipoprotein A-1 (Apo A-1) – either in combination with a statin or as monotherapy, including in patients who cannot tolerate statins. The proposed dose is 75 mg administered subcutaneously every 2 weeks (or a starting dose of 150 mg every 2 weeks for patients who need more than a 60% reduction in LDL-C.

Dr. Brendan Everett, director of the cardiology inpatient service at Brigham and Women’s Hospital, Boston, voted for approval, because of the drug’s potential benefits for patients with heterozygous FH, but added that he would restrict approval to these patients, and did not support approval in other patients, such as those with mixed dyslipidemia.

Alirocumab was compared with placebo or ezetimibe in 10 phase III studies of about 5,100 patients, including those at high CV risk and statin-intolerant patients.

The percent reduction in LDL cholesterol at 24 weeks, from baseline, was the primary endpoint. Summarizing the FDA’s view on the safety and efficacy of alirocumab, Dr. Julie Golden, a medical reviewer in the FDA’s division of metabolism and endocrinology products, said that the agency agrees with the manufacturer, that alirocumab is associated with “substantial and persistent” cholesterol-lowering effects, compared with controls, in all patient populations studied. However, any conclusions about CV benefits are “premature,” she said.

Panelists said that in the studies, there were “weak” safety signals for neurocognitive effects, diabetes, and abnormal liver enzymes, but they were somewhat reassured by the absence of any “highly concerning” adverse events in the studies. Panelists said there was little or no evidence that very low levels of LDL cholesterol are harmful, but that did not provide assurance of safety of very low levels. Several panelists raised the concern that statins may be reduced or stopped in patients whose LDL cholesterol levels dropped to very low levels while on alirocumab, instead of stopping treatment with alirocumab.

Over 20 years, the FDA has accepted reductions in LDL cholesterol as a surrogate for CV risk reduction to support approval of lipid-lowering drugs, but once approved, CV outcomes trials are not required. One of the panelists voting against approval was Dr. Peter Wilson, professor of medicine and public health, Emory University, who said that cardiovascular outcomes data were needed to support approval. “I no longer think we are in an LDL-surrogate era,” he noted.

The alirocumab CV outcomes study – the ODYSSEY Outcomes trial – is enrolling 18,000 patients with recent acute coronary syndrome who are on high intensity statin treatment and are randomized to alirocumab or placebo; MACE is the primary endpoint. The company expects that enrollment in the outcomes study will be completed this year and results will be available in 2017; it will represent 50,000 patient years of experience (vs. 5,000 patient years with the phase III trials) and will include further evaluation of the risks associated with treatment.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists had no potential conflicts of interest.

If approved, Sanofi and Regeneron plan to market alirocumab as Praluent; a decision is expected by July 24th.

On June 10, the panel will review evolocumab, another PCSK9-inhibitor. If approved, these will be the first drugs in this new class of lipid-lowering agents to be approved in the United States. They are human monoclonal antibodies that bind to proprotein convertase subtilisin kexin type 9 (PCSK9), a serine protease that is involved in the regulation of LDL receptor (LDR-R). Inactivation of PCSK9 results in an increase of LDL-R available to clear LDL-C, reducing LDL-C levels.

[email protected]

GAITHERSBURG, MD. – The majority of a Food and Drug Administration Advisory panel has supported the approval of alirocumab, a biologic lipid-lowering drug injected subcutaneously twice a month, as a long-term treatment for hypercholesterolemia, but support for the different patient populations included in the proposed indication varied.

At a meeting on June 9, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13-3 that the manufacturer had “sufficiently established that the LDL cholesterol–lowering benefit of alirocumab exceeds its risks,” and to “support approval in one or more patient populations,” the question posed to the panel. However, those voting in favor of approval said the optimal benefit would be in patients with familial hypercholesterolemia; there was also support among some panelists for patients who are truly statin intolerant and those who cannot get to goal on statin therapy alone and are at a high cardiovascular risk.

Elizabeth Mechcatie/Frontline Medical News

The proposed indication for the PCSK9-inhibitor is for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes, to reduce LDL cholesterol, total cholesterol, non-HDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein A, and to increase HDL cholesterol and apolipoprotein A-1 (Apo A-1) – either in combination with a statin or as monotherapy, including in patients who cannot tolerate statins. The proposed dose is 75 mg administered subcutaneously every 2 weeks (or a starting dose of 150 mg every 2 weeks for patients who need more than a 60% reduction in LDL-C.

Dr. Brendan Everett, director of the cardiology inpatient service at Brigham and Women’s Hospital, Boston, voted for approval, because of the drug’s potential benefits for patients with heterozygous FH, but added that he would restrict approval to these patients, and did not support approval in other patients, such as those with mixed dyslipidemia.

Alirocumab was compared with placebo or ezetimibe in 10 phase III studies of about 5,100 patients, including those at high CV risk and statin-intolerant patients.

The percent reduction in LDL cholesterol at 24 weeks, from baseline, was the primary endpoint. Summarizing the FDA’s view on the safety and efficacy of alirocumab, Dr. Julie Golden, a medical reviewer in the FDA’s division of metabolism and endocrinology products, said that the agency agrees with the manufacturer, that alirocumab is associated with “substantial and persistent” cholesterol-lowering effects, compared with controls, in all patient populations studied. However, any conclusions about CV benefits are “premature,” she said.

Panelists said that in the studies, there were “weak” safety signals for neurocognitive effects, diabetes, and abnormal liver enzymes, but they were somewhat reassured by the absence of any “highly concerning” adverse events in the studies. Panelists said there was little or no evidence that very low levels of LDL cholesterol are harmful, but that did not provide assurance of safety of very low levels. Several panelists raised the concern that statins may be reduced or stopped in patients whose LDL cholesterol levels dropped to very low levels while on alirocumab, instead of stopping treatment with alirocumab.

Over 20 years, the FDA has accepted reductions in LDL cholesterol as a surrogate for CV risk reduction to support approval of lipid-lowering drugs, but once approved, CV outcomes trials are not required. One of the panelists voting against approval was Dr. Peter Wilson, professor of medicine and public health, Emory University, who said that cardiovascular outcomes data were needed to support approval. “I no longer think we are in an LDL-surrogate era,” he noted.

The alirocumab CV outcomes study – the ODYSSEY Outcomes trial – is enrolling 18,000 patients with recent acute coronary syndrome who are on high intensity statin treatment and are randomized to alirocumab or placebo; MACE is the primary endpoint. The company expects that enrollment in the outcomes study will be completed this year and results will be available in 2017; it will represent 50,000 patient years of experience (vs. 5,000 patient years with the phase III trials) and will include further evaluation of the risks associated with treatment.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists had no potential conflicts of interest.

If approved, Sanofi and Regeneron plan to market alirocumab as Praluent; a decision is expected by July 24th.

On June 10, the panel will review evolocumab, another PCSK9-inhibitor. If approved, these will be the first drugs in this new class of lipid-lowering agents to be approved in the United States. They are human monoclonal antibodies that bind to proprotein convertase subtilisin kexin type 9 (PCSK9), a serine protease that is involved in the regulation of LDL receptor (LDR-R). Inactivation of PCSK9 results in an increase of LDL-R available to clear LDL-C, reducing LDL-C levels.

[email protected]

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

[email protected]

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

[email protected]

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

[email protected]

This week, an expert panel convened by the Food and Drug Administration will vote on whether two biologic lipid-lowering treatments, administered subcutaneously every 2 weeks, should be approved for lowering low-density lipoprotein cholesterol (LDL-C) in different groups of patients.

Alirocumab and evolocumab are human monoclonal antibodies that bind to proprotein convertase subtilisin kexin type 9 (PCSK9), a serine protease that is involved in the regulation of LDL receptor (LDR-R). Inactivation of PCSK9 results in an increase of LDL-R available to clear LDL-C, reducing LDL-C levels. If approved, they will be the first PCSK9 inhibitors, a new class of lipid-lowering agents, to be approved in the United States.

The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee will review alirocumab, developed by Sanofi and Regeneron, on June 9, and will review evolocumab, developed by Amgen, on June 10.

The votes on whether the data on the drugs support approval will be based on whether the LDL-C–lowering benefits of the drugs exceed their risks, since lipid-lowering drugs are currently approved using the LDL-C endpoint as a surrogate for cardiovascular benefit, “provided the reduction is sufficiently robust and the product (or its class) does not have safety issues that raise concern that risk exceeds benefit,” according to the FDA draft questions.

For each drug separately, however, the FDA also is asking the panel to discuss whether their LDL-C–lowering effects are “sufficient to substitute for demonstrating its effect on clinical outcomes,” such as a evidence from a cardiovascular outcome trial.

Promising CV outcomes data are available for both drugs, but CV outcomes trials have not been completed and those data are not addressed in the questions.

 Alirocumab

The Sanofi/Regeneron briefing document proposes that alirocumab be approved before the results of the ongoing 18,000-patient CV outcomes study – the ODYSSEY Outcomes trial – are available, and that approval “at this time is based on the unmet needs of patients for additional LDL-C lowering, the demonstration of substantial LDL-C lowering by alirocumab, and an acceptable safety profile.” Patients enrolled in the ODYSSEY Outcomes study have recent acute coronary syndrome, are on high intensity statin treatment, and are randomized to alirocumab or placebo.

Two different dose regimens of alirocumab have been studied in 10 multicenter phase III studies – the ODYSSEY program – which include five 12- to 18-month placebo-controlled studies in about 3,500 patients and five 6- to 24-month studies comparing alirocumab with ezetimibe in about 1,800 patients, which evaluated the percent change in LDL-C at 24 months as the primary endpoint.

The FDA’s briefing document posted before the meeting states that, in studies, alirocumab “demonstrated early and sustained LDL-C lowering from baseline across patient populations, regardless of background lipid-modifying therapies, and is generally well-tolerated.” Treatment was associated with reductions of LDL-C ranging from 36% to 61% from baseline, and differences of 39%-62%, compared with placebo – which were statistically significant – and differences of 24%-36%, compared with ezetimibe. Differences over ezetimibe were statistically significant in all but one of the five studies using ezetimibe as the comparator.

The rate of serious adverse events among those who received alirocumab in placebo-controlled studies were similar to placebo (about 14%) but were slightly higher, compared with ezetimibe (13.1% vs. 11.2%). Rash and pruritus were the most common adverse events associated with alirocumab.

Compared with fewer than 1% of those on controls, about 20% of those treated with alirocumab had at least one LDL-C value that dropped below 15 mg/dL and about 40% had one value that dropped below 25 mg/dL. So far, a review of adverse events “divided by levels of LDL-C achieved did not demonstrate a safety signal,” but patients have not been treated long enough to determine what “if any, adverse effects of prolonged exposure to very low levels of LDL-C will be,” according to the FDA briefing document.

The proposed indication for alirocumab is for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes, to reduce LDL-C, total cholesterol, non–high-density lipoprotein C, apolipoprotein B, triglycerides, and lipoprotein (a) [Lp(a)], and to increase HDL cholesterol and apolipoprotein A-1(Apo A-1). It is proposed for use in combination with a statin, with or without another lipid-modifying therapy, and as monotherapy, or as add-on to other nonstatin lipid-modifying therapy, including in patients who cannot tolerate statins. The proposed dose is 75 mg administered subcutaneously every 2 weeks (or a starting dose of 150 mg every 2 weeks for patients who need more than a 60% reduction in LDL-C).

 Evolocumab

This month, Amgen expects to complete enrollment of FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a CV outcomes study of about 27,500 patients, which started in 2013 and should end by 2017. This also will provide safety data in more than 5,000 patients with LDL-C levels below 40 mg/dL, according to Amgen’s briefing documents posted on the FDA website before the meeting.

The Amgen data include four 12-week double-blind randomized studies comparing evolocumab to placebo or ezetimibe in about 3,100 patients. Both dosing regimens resulted in significantly lower LDL-C levels from baseline, compared with placebo and ezetimibe.

In studies of over 6,000 patients with primary hyperlipidemia or mixed dyslipidemia, evolocumab resulted in LDL-C reductions of 55%-75% compared with placebo, and 35%-45% compared with ezetimibe, according to Amgen. In studies of patients with homozygous familial hypercholesterolemia (HoFH), treatment was associated with LDL-C reductions of about 30%, compared with placebo. To date, no safety risk has been identified with low LDL-C levels in patients with levels that dropped below 25 mg/dL or 40 mg/dL, compared with levels of 40 mg/dL or greater, according to the company.

The proposed indication for evolocumab includes treatment of adults with hyperlipidemia or mixed dyslipidemia. Treatment would be in combination with a statin or a statin with other lipid-lowering therapies, or alone, or in combination with other lipid-lowering therapies in patients who are statin intolerant, or alone or in combination with other lipid-lowering therapies in patients for whom a statin is not considered clinically appropriate. It also is being reviewed for treatment of patients with HoFH who are aged 12 years and older in combination with other lipid-lowering therapies. The recommended doses for adults with primary hyperlipidemia and mixed dyslipidemia are 140 mg every 2 weeks or 420 mg once a month; 420 mg every 2 or 4 weeks is recommended for those with HoFH.

If approved, Sanofi and Regeneron plan to market alirocumab as Praluent and Amgen plans to market evolocumab as Repatha.

[email protected]

This week, an expert panel convened by the Food and Drug Administration will vote on whether two biologic lipid-lowering treatments, administered subcutaneously every 2 weeks, should be approved for lowering low-density lipoprotein cholesterol (LDL-C) in different groups of patients.

Alirocumab and evolocumab are human monoclonal antibodies that bind to proprotein convertase subtilisin kexin type 9 (PCSK9), a serine protease that is involved in the regulation of LDL receptor (LDR-R). Inactivation of PCSK9 results in an increase of LDL-R available to clear LDL-C, reducing LDL-C levels. If approved, they will be the first PCSK9 inhibitors, a new class of lipid-lowering agents, to be approved in the United States.

The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee will review alirocumab, developed by Sanofi and Regeneron, on June 9, and will review evolocumab, developed by Amgen, on June 10.

The votes on whether the data on the drugs support approval will be based on whether the LDL-C–lowering benefits of the drugs exceed their risks, since lipid-lowering drugs are currently approved using the LDL-C endpoint as a surrogate for cardiovascular benefit, “provided the reduction is sufficiently robust and the product (or its class) does not have safety issues that raise concern that risk exceeds benefit,” according to the FDA draft questions.

For each drug separately, however, the FDA also is asking the panel to discuss whether their LDL-C–lowering effects are “sufficient to substitute for demonstrating its effect on clinical outcomes,” such as a evidence from a cardiovascular outcome trial.

Promising CV outcomes data are available for both drugs, but CV outcomes trials have not been completed and those data are not addressed in the questions.

 Alirocumab

The Sanofi/Regeneron briefing document proposes that alirocumab be approved before the results of the ongoing 18,000-patient CV outcomes study – the ODYSSEY Outcomes trial – are available, and that approval “at this time is based on the unmet needs of patients for additional LDL-C lowering, the demonstration of substantial LDL-C lowering by alirocumab, and an acceptable safety profile.” Patients enrolled in the ODYSSEY Outcomes study have recent acute coronary syndrome, are on high intensity statin treatment, and are randomized to alirocumab or placebo.

Two different dose regimens of alirocumab have been studied in 10 multicenter phase III studies – the ODYSSEY program – which include five 12- to 18-month placebo-controlled studies in about 3,500 patients and five 6- to 24-month studies comparing alirocumab with ezetimibe in about 1,800 patients, which evaluated the percent change in LDL-C at 24 months as the primary endpoint.

The FDA’s briefing document posted before the meeting states that, in studies, alirocumab “demonstrated early and sustained LDL-C lowering from baseline across patient populations, regardless of background lipid-modifying therapies, and is generally well-tolerated.” Treatment was associated with reductions of LDL-C ranging from 36% to 61% from baseline, and differences of 39%-62%, compared with placebo – which were statistically significant – and differences of 24%-36%, compared with ezetimibe. Differences over ezetimibe were statistically significant in all but one of the five studies using ezetimibe as the comparator.

The rate of serious adverse events among those who received alirocumab in placebo-controlled studies were similar to placebo (about 14%) but were slightly higher, compared with ezetimibe (13.1% vs. 11.2%). Rash and pruritus were the most common adverse events associated with alirocumab.

Compared with fewer than 1% of those on controls, about 20% of those treated with alirocumab had at least one LDL-C value that dropped below 15 mg/dL and about 40% had one value that dropped below 25 mg/dL. So far, a review of adverse events “divided by levels of LDL-C achieved did not demonstrate a safety signal,” but patients have not been treated long enough to determine what “if any, adverse effects of prolonged exposure to very low levels of LDL-C will be,” according to the FDA briefing document.

The proposed indication for alirocumab is for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes, to reduce LDL-C, total cholesterol, non–high-density lipoprotein C, apolipoprotein B, triglycerides, and lipoprotein (a) [Lp(a)], and to increase HDL cholesterol and apolipoprotein A-1(Apo A-1). It is proposed for use in combination with a statin, with or without another lipid-modifying therapy, and as monotherapy, or as add-on to other nonstatin lipid-modifying therapy, including in patients who cannot tolerate statins. The proposed dose is 75 mg administered subcutaneously every 2 weeks (or a starting dose of 150 mg every 2 weeks for patients who need more than a 60% reduction in LDL-C).

 Evolocumab

This month, Amgen expects to complete enrollment of FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a CV outcomes study of about 27,500 patients, which started in 2013 and should end by 2017. This also will provide safety data in more than 5,000 patients with LDL-C levels below 40 mg/dL, according to Amgen’s briefing documents posted on the FDA website before the meeting.

The Amgen data include four 12-week double-blind randomized studies comparing evolocumab to placebo or ezetimibe in about 3,100 patients. Both dosing regimens resulted in significantly lower LDL-C levels from baseline, compared with placebo and ezetimibe.

In studies of over 6,000 patients with primary hyperlipidemia or mixed dyslipidemia, evolocumab resulted in LDL-C reductions of 55%-75% compared with placebo, and 35%-45% compared with ezetimibe, according to Amgen. In studies of patients with homozygous familial hypercholesterolemia (HoFH), treatment was associated with LDL-C reductions of about 30%, compared with placebo. To date, no safety risk has been identified with low LDL-C levels in patients with levels that dropped below 25 mg/dL or 40 mg/dL, compared with levels of 40 mg/dL or greater, according to the company.

The proposed indication for evolocumab includes treatment of adults with hyperlipidemia or mixed dyslipidemia. Treatment would be in combination with a statin or a statin with other lipid-lowering therapies, or alone, or in combination with other lipid-lowering therapies in patients who are statin intolerant, or alone or in combination with other lipid-lowering therapies in patients for whom a statin is not considered clinically appropriate. It also is being reviewed for treatment of patients with HoFH who are aged 12 years and older in combination with other lipid-lowering therapies. The recommended doses for adults with primary hyperlipidemia and mixed dyslipidemia are 140 mg every 2 weeks or 420 mg once a month; 420 mg every 2 or 4 weeks is recommended for those with HoFH.

If approved, Sanofi and Regeneron plan to market alirocumab as Praluent and Amgen plans to market evolocumab as Repatha.

[email protected]

This week, an expert panel convened by the Food and Drug Administration will vote on whether two biologic lipid-lowering treatments, administered subcutaneously every 2 weeks, should be approved for lowering low-density lipoprotein cholesterol (LDL-C) in different groups of patients.

Alirocumab and evolocumab are human monoclonal antibodies that bind to proprotein convertase subtilisin kexin type 9 (PCSK9), a serine protease that is involved in the regulation of LDL receptor (LDR-R). Inactivation of PCSK9 results in an increase of LDL-R available to clear LDL-C, reducing LDL-C levels. If approved, they will be the first PCSK9 inhibitors, a new class of lipid-lowering agents, to be approved in the United States.

The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee will review alirocumab, developed by Sanofi and Regeneron, on June 9, and will review evolocumab, developed by Amgen, on June 10.

The votes on whether the data on the drugs support approval will be based on whether the LDL-C–lowering benefits of the drugs exceed their risks, since lipid-lowering drugs are currently approved using the LDL-C endpoint as a surrogate for cardiovascular benefit, “provided the reduction is sufficiently robust and the product (or its class) does not have safety issues that raise concern that risk exceeds benefit,” according to the FDA draft questions.

For each drug separately, however, the FDA also is asking the panel to discuss whether their LDL-C–lowering effects are “sufficient to substitute for demonstrating its effect on clinical outcomes,” such as a evidence from a cardiovascular outcome trial.

Promising CV outcomes data are available for both drugs, but CV outcomes trials have not been completed and those data are not addressed in the questions.

 Alirocumab

The Sanofi/Regeneron briefing document proposes that alirocumab be approved before the results of the ongoing 18,000-patient CV outcomes study – the ODYSSEY Outcomes trial – are available, and that approval “at this time is based on the unmet needs of patients for additional LDL-C lowering, the demonstration of substantial LDL-C lowering by alirocumab, and an acceptable safety profile.” Patients enrolled in the ODYSSEY Outcomes study have recent acute coronary syndrome, are on high intensity statin treatment, and are randomized to alirocumab or placebo.

Two different dose regimens of alirocumab have been studied in 10 multicenter phase III studies – the ODYSSEY program – which include five 12- to 18-month placebo-controlled studies in about 3,500 patients and five 6- to 24-month studies comparing alirocumab with ezetimibe in about 1,800 patients, which evaluated the percent change in LDL-C at 24 months as the primary endpoint.

The FDA’s briefing document posted before the meeting states that, in studies, alirocumab “demonstrated early and sustained LDL-C lowering from baseline across patient populations, regardless of background lipid-modifying therapies, and is generally well-tolerated.” Treatment was associated with reductions of LDL-C ranging from 36% to 61% from baseline, and differences of 39%-62%, compared with placebo – which were statistically significant – and differences of 24%-36%, compared with ezetimibe. Differences over ezetimibe were statistically significant in all but one of the five studies using ezetimibe as the comparator.

The rate of serious adverse events among those who received alirocumab in placebo-controlled studies were similar to placebo (about 14%) but were slightly higher, compared with ezetimibe (13.1% vs. 11.2%). Rash and pruritus were the most common adverse events associated with alirocumab.

Compared with fewer than 1% of those on controls, about 20% of those treated with alirocumab had at least one LDL-C value that dropped below 15 mg/dL and about 40% had one value that dropped below 25 mg/dL. So far, a review of adverse events “divided by levels of LDL-C achieved did not demonstrate a safety signal,” but patients have not been treated long enough to determine what “if any, adverse effects of prolonged exposure to very low levels of LDL-C will be,” according to the FDA briefing document.

The proposed indication for alirocumab is for treating adults with primary hypercholesterolemia (nonfamilial and heterozygous familial) or mixed dyslipidemia, including patients with type 2 diabetes, to reduce LDL-C, total cholesterol, non–high-density lipoprotein C, apolipoprotein B, triglycerides, and lipoprotein (a) [Lp(a)], and to increase HDL cholesterol and apolipoprotein A-1(Apo A-1). It is proposed for use in combination with a statin, with or without another lipid-modifying therapy, and as monotherapy, or as add-on to other nonstatin lipid-modifying therapy, including in patients who cannot tolerate statins. The proposed dose is 75 mg administered subcutaneously every 2 weeks (or a starting dose of 150 mg every 2 weeks for patients who need more than a 60% reduction in LDL-C).

 Evolocumab

This month, Amgen expects to complete enrollment of FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a CV outcomes study of about 27,500 patients, which started in 2013 and should end by 2017. This also will provide safety data in more than 5,000 patients with LDL-C levels below 40 mg/dL, according to Amgen’s briefing documents posted on the FDA website before the meeting.

The Amgen data include four 12-week double-blind randomized studies comparing evolocumab to placebo or ezetimibe in about 3,100 patients. Both dosing regimens resulted in significantly lower LDL-C levels from baseline, compared with placebo and ezetimibe.

In studies of over 6,000 patients with primary hyperlipidemia or mixed dyslipidemia, evolocumab resulted in LDL-C reductions of 55%-75% compared with placebo, and 35%-45% compared with ezetimibe, according to Amgen. In studies of patients with homozygous familial hypercholesterolemia (HoFH), treatment was associated with LDL-C reductions of about 30%, compared with placebo. To date, no safety risk has been identified with low LDL-C levels in patients with levels that dropped below 25 mg/dL or 40 mg/dL, compared with levels of 40 mg/dL or greater, according to the company.

The proposed indication for evolocumab includes treatment of adults with hyperlipidemia or mixed dyslipidemia. Treatment would be in combination with a statin or a statin with other lipid-lowering therapies, or alone, or in combination with other lipid-lowering therapies in patients who are statin intolerant, or alone or in combination with other lipid-lowering therapies in patients for whom a statin is not considered clinically appropriate. It also is being reviewed for treatment of patients with HoFH who are aged 12 years and older in combination with other lipid-lowering therapies. The recommended doses for adults with primary hyperlipidemia and mixed dyslipidemia are 140 mg every 2 weeks or 420 mg once a month; 420 mg every 2 or 4 weeks is recommended for those with HoFH.

If approved, Sanofi and Regeneron plan to market alirocumab as Praluent and Amgen plans to market evolocumab as Repatha.

[email protected]

BOSTON – The glucose-lowering drug sitagliptin, part of a class of drugs whose cardiovascular safety has been cast into doubt based on findings in trials of similar agents, was shown not to increase the risk of heart failure or other adverse cardiovascular outcomes in a large randomized trial.

Results presented June 8 at the annual scientific sessions of the American Diabetes Association and published simultaneously in the New England Journal of Medicine (doi:10.1056/NEJMoa1501352) revealed “no evidence of harm one way or another” for cardiovascular events or heart failure, Dr. Rury F. Holman, professor of diabetic medicine and diabetes trials unit director at the Oxford (England) Centre for Diabetes, Endocrinology & Metabolism, the study’s corresponding author, said at a press conference.

Though the manufacturer announced the main cardiovascular findings on sitagliptin (Januvia), earlier this year, the details of this trial – driven by concerns about a signal for increased risk of heart failure in two earlier trials of dipeptidyl peptidase 4 (DPP-4) inhibitors – were presented for the first time.

TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) enrolled 14,671 patients with type 2 diabetes in combination with cardiovascular disease who were age 50 years or older. Patients were recruited in 38 countries and randomized to add-on therapy with

sitagliptin or placebo in addition to other antihyperglycemic therapies used openly at physician discretion. At mean 3 years’ follow-up, sitagliptin was noninferior to placebo for a combined cardiovascular endpoint comprising first time to CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09, P < .001).

Hospitalizations for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.83-1.20, P = .98), and no significant differences were seen in rates of pancreatitis or pancreatic cancer.

All patients in both the control and intervention arms were treated to similar glucose targets by their physicians. Levels of glycated hemoglobin between the groups were close throughout the study period, with a difference of –0.29 for the sitagliptin arm (95% CI, –0.32 to –0.27). “That’s important because we didn’t want a glucose difference that might have influenced the cardiovascular outcomes one way or another,” Dr. Holman commented.

Dr. Eric D. Peterson, executive director of the Duke Clinical Research Institute as well as professor in the departments of medicine and cardiology and the Fred Cobb, MD, Distinguished Professor of Medicine of Duke University, Durham, N.C., who was a coauthor on the study, commented on its heart failure finding. TECOS had been prompted by unexpected

heart-failure signals seen in two earlier trials of DPP-4 inhibitors, saxagliptin and alogliptin.

“Given the size of our study, and the longer duration of follow-up, as well as the higher risk of our population, we feel that this puts to bed the question – at least with sitagliptin – that there’s any risk for heart failure increases,” Dr. Peterson said.

The investigators were careful to assert that few conclusions could be drawn for the class of drugs as a whole based on the TECOS findings but suggested chance could have played a role in the earlier studies.

The study was funded by sitagliptin’s manufacturer, Merck Sharp & Dohme. Dr. Holman disclosed a financial relationship with the study sponsor. Dr. Peterson disclosed financial relationships with other manufacturers.

BOSTON – The glucose-lowering drug sitagliptin, part of a class of drugs whose cardiovascular safety has been cast into doubt based on findings in trials of similar agents, was shown not to increase the risk of heart failure or other adverse cardiovascular outcomes in a large randomized trial.

Results presented June 8 at the annual scientific sessions of the American Diabetes Association and published simultaneously in the New England Journal of Medicine (doi:10.1056/NEJMoa1501352) revealed “no evidence of harm one way or another” for cardiovascular events or heart failure, Dr. Rury F. Holman, professor of diabetic medicine and diabetes trials unit director at the Oxford (England) Centre for Diabetes, Endocrinology & Metabolism, the study’s corresponding author, said at a press conference.

Though the manufacturer announced the main cardiovascular findings on sitagliptin (Januvia), earlier this year, the details of this trial – driven by concerns about a signal for increased risk of heart failure in two earlier trials of dipeptidyl peptidase 4 (DPP-4) inhibitors – were presented for the first time.

TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) enrolled 14,671 patients with type 2 diabetes in combination with cardiovascular disease who were age 50 years or older. Patients were recruited in 38 countries and randomized to add-on therapy with

sitagliptin or placebo in addition to other antihyperglycemic therapies used openly at physician discretion. At mean 3 years’ follow-up, sitagliptin was noninferior to placebo for a combined cardiovascular endpoint comprising first time to CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09, P < .001).

Hospitalizations for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.83-1.20, P = .98), and no significant differences were seen in rates of pancreatitis or pancreatic cancer.

All patients in both the control and intervention arms were treated to similar glucose targets by their physicians. Levels of glycated hemoglobin between the groups were close throughout the study period, with a difference of –0.29 for the sitagliptin arm (95% CI, –0.32 to –0.27). “That’s important because we didn’t want a glucose difference that might have influenced the cardiovascular outcomes one way or another,” Dr. Holman commented.

Dr. Eric D. Peterson, executive director of the Duke Clinical Research Institute as well as professor in the departments of medicine and cardiology and the Fred Cobb, MD, Distinguished Professor of Medicine of Duke University, Durham, N.C., who was a coauthor on the study, commented on its heart failure finding. TECOS had been prompted by unexpected

heart-failure signals seen in two earlier trials of DPP-4 inhibitors, saxagliptin and alogliptin.

“Given the size of our study, and the longer duration of follow-up, as well as the higher risk of our population, we feel that this puts to bed the question – at least with sitagliptin – that there’s any risk for heart failure increases,” Dr. Peterson said.

The investigators were careful to assert that few conclusions could be drawn for the class of drugs as a whole based on the TECOS findings but suggested chance could have played a role in the earlier studies.

The study was funded by sitagliptin’s manufacturer, Merck Sharp & Dohme. Dr. Holman disclosed a financial relationship with the study sponsor. Dr. Peterson disclosed financial relationships with other manufacturers.

BOSTON – The glucose-lowering drug sitagliptin, part of a class of drugs whose cardiovascular safety has been cast into doubt based on findings in trials of similar agents, was shown not to increase the risk of heart failure or other adverse cardiovascular outcomes in a large randomized trial.

Results presented June 8 at the annual scientific sessions of the American Diabetes Association and published simultaneously in the New England Journal of Medicine (doi:10.1056/NEJMoa1501352) revealed “no evidence of harm one way or another” for cardiovascular events or heart failure, Dr. Rury F. Holman, professor of diabetic medicine and diabetes trials unit director at the Oxford (England) Centre for Diabetes, Endocrinology & Metabolism, the study’s corresponding author, said at a press conference.

Though the manufacturer announced the main cardiovascular findings on sitagliptin (Januvia), earlier this year, the details of this trial – driven by concerns about a signal for increased risk of heart failure in two earlier trials of dipeptidyl peptidase 4 (DPP-4) inhibitors – were presented for the first time.

TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) enrolled 14,671 patients with type 2 diabetes in combination with cardiovascular disease who were age 50 years or older. Patients were recruited in 38 countries and randomized to add-on therapy with

sitagliptin or placebo in addition to other antihyperglycemic therapies used openly at physician discretion. At mean 3 years’ follow-up, sitagliptin was noninferior to placebo for a combined cardiovascular endpoint comprising first time to CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09, P < .001).

Hospitalizations for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.83-1.20, P = .98), and no significant differences were seen in rates of pancreatitis or pancreatic cancer.

All patients in both the control and intervention arms were treated to similar glucose targets by their physicians. Levels of glycated hemoglobin between the groups were close throughout the study period, with a difference of –0.29 for the sitagliptin arm (95% CI, –0.32 to –0.27). “That’s important because we didn’t want a glucose difference that might have influenced the cardiovascular outcomes one way or another,” Dr. Holman commented.

Dr. Eric D. Peterson, executive director of the Duke Clinical Research Institute as well as professor in the departments of medicine and cardiology and the Fred Cobb, MD, Distinguished Professor of Medicine of Duke University, Durham, N.C., who was a coauthor on the study, commented on its heart failure finding. TECOS had been prompted by unexpected

heart-failure signals seen in two earlier trials of DPP-4 inhibitors, saxagliptin and alogliptin.

“Given the size of our study, and the longer duration of follow-up, as well as the higher risk of our population, we feel that this puts to bed the question – at least with sitagliptin – that there’s any risk for heart failure increases,” Dr. Peterson said.

The investigators were careful to assert that few conclusions could be drawn for the class of drugs as a whole based on the TECOS findings but suggested chance could have played a role in the earlier studies.

The study was funded by sitagliptin’s manufacturer, Merck Sharp & Dohme. Dr. Holman disclosed a financial relationship with the study sponsor. Dr. Peterson disclosed financial relationships with other manufacturers.

BOSTON – Weight loss was greater with laparoscopic adjustable gastric banding than with an intensive lifestyle intervention among obese patients with type 2 diabetes in a randomized clinical trial, but the effects on diabetes control, cardiometabolic risk, and quality of life were comparable.

Weight loss in 18 patients randomized to undergo the bariatric surgery was an average of 13.5 lb at 12 months’ follow-up, compared with 8.5 lb in those randomized to the active component of the study: a 12-week lifestyle intervention (Weight Achievement and Intensive Treatment–the Why WAIT program), Dr. Osama Hamdy reported in a poster at the annual scientific sessions of the American Diabetes Association.

However, hemogobin A_1c reduction was similar in the two groups at –1.2% vs. –1%, respectively. Further, improvements in blood pressure, triglycerides, and low-density lipoprotein levels did not differ between the groups, said Dr. Hamdy, medical director of the obesity clinical program, and director of the inpatient program at Joslin Diabetes Clinic, Harvard Medical School, Boston.

The risk of fatal coronary heart disease events also decreased in both groups, from 6.5% to 5.9% in the bariatric surgery group, and from 5.8% to 5.5% in the Why WAIT group; the difference between the groups was not statistically significant, he said.

Quality of life as assessed by the 36-item Short Form Survey’s physical and mental health summary measures changed only slightly from baseline in both groups, with no between-group differences. Similarly, scores on the Impact of Weight on Quality of Life and on Problem Areas in Diabetes improved significantly in both groups, but no between-group differences were seen.

“These findings suggest that the Why WAIT program and laparoscopic adjustable gastric banding have similar benefits for diabetes control, cardiometabolic risk, and quality of life parameters,” according to Dr. Hamdy, who noted that the findings may be useful for guiding obese patients with type 2 diabetes as they explore weight management options.

Dr. Hamdy reported that he has received research support and is an advisory panel member and author for Metagenics, that he is a consultant and author for Abbott Nutrition and Merck, and that he has received research support and is an author for Neurometrix.

[email protected]

BOSTON – Weight loss was greater with laparoscopic adjustable gastric banding than with an intensive lifestyle intervention among obese patients with type 2 diabetes in a randomized clinical trial, but the effects on diabetes control, cardiometabolic risk, and quality of life were comparable.

Weight loss in 18 patients randomized to undergo the bariatric surgery was an average of 13.5 lb at 12 months’ follow-up, compared with 8.5 lb in those randomized to the active component of the study: a 12-week lifestyle intervention (Weight Achievement and Intensive Treatment–the Why WAIT program), Dr. Osama Hamdy reported in a poster at the annual scientific sessions of the American Diabetes Association.

However, hemogobin A_1c reduction was similar in the two groups at –1.2% vs. –1%, respectively. Further, improvements in blood pressure, triglycerides, and low-density lipoprotein levels did not differ between the groups, said Dr. Hamdy, medical director of the obesity clinical program, and director of the inpatient program at Joslin Diabetes Clinic, Harvard Medical School, Boston.

The risk of fatal coronary heart disease events also decreased in both groups, from 6.5% to 5.9% in the bariatric surgery group, and from 5.8% to 5.5% in the Why WAIT group; the difference between the groups was not statistically significant, he said.

Quality of life as assessed by the 36-item Short Form Survey’s physical and mental health summary measures changed only slightly from baseline in both groups, with no between-group differences. Similarly, scores on the Impact of Weight on Quality of Life and on Problem Areas in Diabetes improved significantly in both groups, but no between-group differences were seen.

“These findings suggest that the Why WAIT program and laparoscopic adjustable gastric banding have similar benefits for diabetes control, cardiometabolic risk, and quality of life parameters,” according to Dr. Hamdy, who noted that the findings may be useful for guiding obese patients with type 2 diabetes as they explore weight management options.

Dr. Hamdy reported that he has received research support and is an advisory panel member and author for Metagenics, that he is a consultant and author for Abbott Nutrition and Merck, and that he has received research support and is an author for Neurometrix.

[email protected]

BOSTON – Weight loss was greater with laparoscopic adjustable gastric banding than with an intensive lifestyle intervention among obese patients with type 2 diabetes in a randomized clinical trial, but the effects on diabetes control, cardiometabolic risk, and quality of life were comparable.

Weight loss in 18 patients randomized to undergo the bariatric surgery was an average of 13.5 lb at 12 months’ follow-up, compared with 8.5 lb in those randomized to the active component of the study: a 12-week lifestyle intervention (Weight Achievement and Intensive Treatment–the Why WAIT program), Dr. Osama Hamdy reported in a poster at the annual scientific sessions of the American Diabetes Association.

However, hemogobin A_1c reduction was similar in the two groups at –1.2% vs. –1%, respectively. Further, improvements in blood pressure, triglycerides, and low-density lipoprotein levels did not differ between the groups, said Dr. Hamdy, medical director of the obesity clinical program, and director of the inpatient program at Joslin Diabetes Clinic, Harvard Medical School, Boston.

The risk of fatal coronary heart disease events also decreased in both groups, from 6.5% to 5.9% in the bariatric surgery group, and from 5.8% to 5.5% in the Why WAIT group; the difference between the groups was not statistically significant, he said.

Quality of life as assessed by the 36-item Short Form Survey’s physical and mental health summary measures changed only slightly from baseline in both groups, with no between-group differences. Similarly, scores on the Impact of Weight on Quality of Life and on Problem Areas in Diabetes improved significantly in both groups, but no between-group differences were seen.

“These findings suggest that the Why WAIT program and laparoscopic adjustable gastric banding have similar benefits for diabetes control, cardiometabolic risk, and quality of life parameters,” according to Dr. Hamdy, who noted that the findings may be useful for guiding obese patients with type 2 diabetes as they explore weight management options.

Dr. Hamdy reported that he has received research support and is an advisory panel member and author for Metagenics, that he is a consultant and author for Abbott Nutrition and Merck, and that he has received research support and is an author for Neurometrix.

[email protected]

BOSTON – Maternal obesity and increased weight gain during pregnancy are associated with changes to newborns’ cardiometabolic markers, and these associations are largely independent of infant adiposity, according to new research findings.

Maternal obesity and weight gain during pregnancy are established risk factors for childhood obesity, but the reasons for this remain little understood.

thinkstockphotos.com

In utero programming of infant metabolism may be occurring, providing reasons beyond fetal growth and fat accretion for the differences in lipid and hormonal profiles among infants, judging from the findings reported at the annual scientific sessions of the American Diabetes Association.

Presenting data from a cohort of 753 mother-infant pairs, Dominick J. Lemas, Ph.D., of the University of Colorado, Denver, said that samples of cord blood revealed “striking” associations.

Dr. Lemas and his colleagues found higher levels of cord blood glucose (P = .03), and leptin (P < .001) in newborns among mothers who gained more weight during pregnancy. Infants of women with higher body mass index when they became pregnant saw higher levels of leptin (P < .001) in cord blood and lower levels of HDL cholesterol (P = .05), even after adjusting for infant adiposity.

The leptin finding was particularly surprising, Dr. Lemas said. Leptin, a hormone that regulates food intake, energy output, and other functions, is synthesized by fatty tissues and therefore expected to be found in higher levels among infants with fatter body composition.

In this study, however, “the association actually became stronger when we adjusted for the adiposity of the infant,” he said.

The investigators looked carefully at cord blood lipids, including total and high-density lipoprotein (HDL) cholesterol, triglycerides, and free fatty acids. The finding that prepregnancy BMI was negatively associated with HDL cholesterol “was something very interesting for our group,” Dr. Lemas said at the conference. “In adults, abnormal lipid patterns are a very strong predictor of cardiovascular disease.”

The findings raise two main concerns, Dr. Lemas said. First, “what factors beyond maternal BMI and gestational weight gain contribute to the changes to these cardiometabolic biomarkers at delivery?” And second, he said, it remains to be seen if these markers persist or result in clinically meaningful differences: “It’s possible cord-blood biomarkers don’t predict the metabolic risk of these individuals a few years down the road.”

The investigators used data from Healthy Start, a cohort study funded by the National Institute of Diabetes and Digestive and Kidney Diseases. They disclosed no conflicts of interest, and the full paper on their findings will be published in the International Journal of Obesity.

BOSTON – Maternal obesity and increased weight gain during pregnancy are associated with changes to newborns’ cardiometabolic markers, and these associations are largely independent of infant adiposity, according to new research findings.

Maternal obesity and weight gain during pregnancy are established risk factors for childhood obesity, but the reasons for this remain little understood.

thinkstockphotos.com

In utero programming of infant metabolism may be occurring, providing reasons beyond fetal growth and fat accretion for the differences in lipid and hormonal profiles among infants, judging from the findings reported at the annual scientific sessions of the American Diabetes Association.

Presenting data from a cohort of 753 mother-infant pairs, Dominick J. Lemas, Ph.D., of the University of Colorado, Denver, said that samples of cord blood revealed “striking” associations.

Dr. Lemas and his colleagues found higher levels of cord blood glucose (P = .03), and leptin (P < .001) in newborns among mothers who gained more weight during pregnancy. Infants of women with higher body mass index when they became pregnant saw higher levels of leptin (P < .001) in cord blood and lower levels of HDL cholesterol (P = .05), even after adjusting for infant adiposity.

The leptin finding was particularly surprising, Dr. Lemas said. Leptin, a hormone that regulates food intake, energy output, and other functions, is synthesized by fatty tissues and therefore expected to be found in higher levels among infants with fatter body composition.

In this study, however, “the association actually became stronger when we adjusted for the adiposity of the infant,” he said.

The investigators looked carefully at cord blood lipids, including total and high-density lipoprotein (HDL) cholesterol, triglycerides, and free fatty acids. The finding that prepregnancy BMI was negatively associated with HDL cholesterol “was something very interesting for our group,” Dr. Lemas said at the conference. “In adults, abnormal lipid patterns are a very strong predictor of cardiovascular disease.”

The findings raise two main concerns, Dr. Lemas said. First, “what factors beyond maternal BMI and gestational weight gain contribute to the changes to these cardiometabolic biomarkers at delivery?” And second, he said, it remains to be seen if these markers persist or result in clinically meaningful differences: “It’s possible cord-blood biomarkers don’t predict the metabolic risk of these individuals a few years down the road.”

The investigators used data from Healthy Start, a cohort study funded by the National Institute of Diabetes and Digestive and Kidney Diseases. They disclosed no conflicts of interest, and the full paper on their findings will be published in the International Journal of Obesity.

BOSTON – Maternal obesity and increased weight gain during pregnancy are associated with changes to newborns’ cardiometabolic markers, and these associations are largely independent of infant adiposity, according to new research findings.

Maternal obesity and weight gain during pregnancy are established risk factors for childhood obesity, but the reasons for this remain little understood.

thinkstockphotos.com

In utero programming of infant metabolism may be occurring, providing reasons beyond fetal growth and fat accretion for the differences in lipid and hormonal profiles among infants, judging from the findings reported at the annual scientific sessions of the American Diabetes Association.

Presenting data from a cohort of 753 mother-infant pairs, Dominick J. Lemas, Ph.D., of the University of Colorado, Denver, said that samples of cord blood revealed “striking” associations.

Dr. Lemas and his colleagues found higher levels of cord blood glucose (P = .03), and leptin (P < .001) in newborns among mothers who gained more weight during pregnancy. Infants of women with higher body mass index when they became pregnant saw higher levels of leptin (P < .001) in cord blood and lower levels of HDL cholesterol (P = .05), even after adjusting for infant adiposity.

The leptin finding was particularly surprising, Dr. Lemas said. Leptin, a hormone that regulates food intake, energy output, and other functions, is synthesized by fatty tissues and therefore expected to be found in higher levels among infants with fatter body composition.

In this study, however, “the association actually became stronger when we adjusted for the adiposity of the infant,” he said.

The investigators looked carefully at cord blood lipids, including total and high-density lipoprotein (HDL) cholesterol, triglycerides, and free fatty acids. The finding that prepregnancy BMI was negatively associated with HDL cholesterol “was something very interesting for our group,” Dr. Lemas said at the conference. “In adults, abnormal lipid patterns are a very strong predictor of cardiovascular disease.”

The findings raise two main concerns, Dr. Lemas said. First, “what factors beyond maternal BMI and gestational weight gain contribute to the changes to these cardiometabolic biomarkers at delivery?” And second, he said, it remains to be seen if these markers persist or result in clinically meaningful differences: “It’s possible cord-blood biomarkers don’t predict the metabolic risk of these individuals a few years down the road.”

The investigators used data from Healthy Start, a cohort study funded by the National Institute of Diabetes and Digestive and Kidney Diseases. They disclosed no conflicts of interest, and the full paper on their findings will be published in the International Journal of Obesity.

NASHVILLE, TENN. – When ordering a fasting blood test for patients with diabetes, it’s prudent to have them cut back on their insulin and oral hypoglycemic agents to avoid hypoglycemia.

Unless they take such protective actions, an estimated half or more will be hypoglycemic by the time their blood is drawn, according to a survey from Michigan State University.

Alex Otto/Frontline Medical News

Of the 74 study participants – mostly people with type 2 diabetes – who have enrolled so far in the ongoing project, 37 (50%) reported overnight fasting for lipid profiles or other tests in the previous year. Just three cut back on their medications, either on their own or on the advice of their doctors. Just over half the subjects were women, about three-quarters had type 2 diabetes, and the average age in the study was 53 years.

Twenty-three of the 37 patients (62%) reported at least one hypoglycemic event while fasting, with plasma glucose falling below 70 mg/dL. Some had up to seven events. Most told their doctors what had happened, but steps weren’t often taken to prevent future events.

“These interim results vividly confirm the occurrence of” fasting hypoglycemia “in clinical practice, and indicate a significant prevalence” among patients with diabetes. “This study serves as a means of increasing awareness about” the problem, “which clinicians appear to overlook,” concluded the investigators, led by Dr. Saleh Aldasouqi, associate professor of medicine and chief of endocrinology at Michigan State, East Lansing.

Dr. Aldasouqi first noticed the problem several years ago when practicing in Cape Girardeau, Mo. He fielded several calls there from nervous lab technicians reporting hypoglycemia in patients with diabetes who had fasted overnight. “We looked at the world literature on this at the time and found zero,” he said, except for a case report of a woman who collapsed and died while waiting for a lipid draw after fasting the night before. Her blood glucose was zero.

That report prompted Dr. Aldasouqi and his colleagues in Cape Girardeau to study the issue. They found that hypoglycemia ranged from 69-30 mg/dL among 35 patients with diabetes who recalled fasting or possibly fasting for a blood test. None recalled adjusting their medications (Diabetes Care 2011;34:e52).

Dr. Aldasouqi dubbed the problem fasting-evoked en-route hypoglycemia in diabetes (FEEHD): “en-route” to invoke the possibility that patients with diabetes might crash if their blood sugar drops too low while driving in for a blood draw, he said at the annual meeting of the American Association of Clinical Endocrinologists.

The next step in Cape Girardeau was a prevention program to monitor blood glucose and adjust medications for patients with diabetes who were fasting for a test. It reduced the incidence of hypoglycemic events by 68%, with an even greater drop in the incidence of severe hypoglycemia below 50 mg/dL (Postgrad. Med. 2013;125:136-43).

“We’ve been trying to build a case” that FEEHD really is a problem, but there’s been some skepticism because “we are trying to change a deeply rooted tradition” and the notion that diabetics can fast just like anyone else. Even so, “people are coming around now that we have data,” Dr. Aldasouqi said. Currently at Michigan State, “my group is not ordering fasting” for lipid tests, although it remains routine in other clinics there. They opted for that approach, instead of reducing diabetes medications during fasts, because of the growing evidence that patients – whether they have diabetes or not – really don’t need to fast for lipid panels, he said (Circulation 2015;131:e471).

There was no external funding for the project. Dr. Aldasouqi is a speaker or adviser for Janssen, Sanofi, and Takeda.

[email protected]

NASHVILLE, TENN. – When ordering a fasting blood test for patients with diabetes, it’s prudent to have them cut back on their insulin and oral hypoglycemic agents to avoid hypoglycemia.

Unless they take such protective actions, an estimated half or more will be hypoglycemic by the time their blood is drawn, according to a survey from Michigan State University.

Alex Otto/Frontline Medical News

Of the 74 study participants – mostly people with type 2 diabetes – who have enrolled so far in the ongoing project, 37 (50%) reported overnight fasting for lipid profiles or other tests in the previous year. Just three cut back on their medications, either on their own or on the advice of their doctors. Just over half the subjects were women, about three-quarters had type 2 diabetes, and the average age in the study was 53 years.

Twenty-three of the 37 patients (62%) reported at least one hypoglycemic event while fasting, with plasma glucose falling below 70 mg/dL. Some had up to seven events. Most told their doctors what had happened, but steps weren’t often taken to prevent future events.

“These interim results vividly confirm the occurrence of” fasting hypoglycemia “in clinical practice, and indicate a significant prevalence” among patients with diabetes. “This study serves as a means of increasing awareness about” the problem, “which clinicians appear to overlook,” concluded the investigators, led by Dr. Saleh Aldasouqi, associate professor of medicine and chief of endocrinology at Michigan State, East Lansing.

Dr. Aldasouqi first noticed the problem several years ago when practicing in Cape Girardeau, Mo. He fielded several calls there from nervous lab technicians reporting hypoglycemia in patients with diabetes who had fasted overnight. “We looked at the world literature on this at the time and found zero,” he said, except for a case report of a woman who collapsed and died while waiting for a lipid draw after fasting the night before. Her blood glucose was zero.

That report prompted Dr. Aldasouqi and his colleagues in Cape Girardeau to study the issue. They found that hypoglycemia ranged from 69-30 mg/dL among 35 patients with diabetes who recalled fasting or possibly fasting for a blood test. None recalled adjusting their medications (Diabetes Care 2011;34:e52).

Dr. Aldasouqi dubbed the problem fasting-evoked en-route hypoglycemia in diabetes (FEEHD): “en-route” to invoke the possibility that patients with diabetes might crash if their blood sugar drops too low while driving in for a blood draw, he said at the annual meeting of the American Association of Clinical Endocrinologists.

The next step in Cape Girardeau was a prevention program to monitor blood glucose and adjust medications for patients with diabetes who were fasting for a test. It reduced the incidence of hypoglycemic events by 68%, with an even greater drop in the incidence of severe hypoglycemia below 50 mg/dL (Postgrad. Med. 2013;125:136-43).

“We’ve been trying to build a case” that FEEHD really is a problem, but there’s been some skepticism because “we are trying to change a deeply rooted tradition” and the notion that diabetics can fast just like anyone else. Even so, “people are coming around now that we have data,” Dr. Aldasouqi said. Currently at Michigan State, “my group is not ordering fasting” for lipid tests, although it remains routine in other clinics there. They opted for that approach, instead of reducing diabetes medications during fasts, because of the growing evidence that patients – whether they have diabetes or not – really don’t need to fast for lipid panels, he said (Circulation 2015;131:e471).

There was no external funding for the project. Dr. Aldasouqi is a speaker or adviser for Janssen, Sanofi, and Takeda.

[email protected]

NASHVILLE, TENN. – When ordering a fasting blood test for patients with diabetes, it’s prudent to have them cut back on their insulin and oral hypoglycemic agents to avoid hypoglycemia.

Unless they take such protective actions, an estimated half or more will be hypoglycemic by the time their blood is drawn, according to a survey from Michigan State University.

Alex Otto/Frontline Medical News

Of the 74 study participants – mostly people with type 2 diabetes – who have enrolled so far in the ongoing project, 37 (50%) reported overnight fasting for lipid profiles or other tests in the previous year. Just three cut back on their medications, either on their own or on the advice of their doctors. Just over half the subjects were women, about three-quarters had type 2 diabetes, and the average age in the study was 53 years.

Twenty-three of the 37 patients (62%) reported at least one hypoglycemic event while fasting, with plasma glucose falling below 70 mg/dL. Some had up to seven events. Most told their doctors what had happened, but steps weren’t often taken to prevent future events.

“These interim results vividly confirm the occurrence of” fasting hypoglycemia “in clinical practice, and indicate a significant prevalence” among patients with diabetes. “This study serves as a means of increasing awareness about” the problem, “which clinicians appear to overlook,” concluded the investigators, led by Dr. Saleh Aldasouqi, associate professor of medicine and chief of endocrinology at Michigan State, East Lansing.

Dr. Aldasouqi first noticed the problem several years ago when practicing in Cape Girardeau, Mo. He fielded several calls there from nervous lab technicians reporting hypoglycemia in patients with diabetes who had fasted overnight. “We looked at the world literature on this at the time and found zero,” he said, except for a case report of a woman who collapsed and died while waiting for a lipid draw after fasting the night before. Her blood glucose was zero.

That report prompted Dr. Aldasouqi and his colleagues in Cape Girardeau to study the issue. They found that hypoglycemia ranged from 69-30 mg/dL among 35 patients with diabetes who recalled fasting or possibly fasting for a blood test. None recalled adjusting their medications (Diabetes Care 2011;34:e52).

Dr. Aldasouqi dubbed the problem fasting-evoked en-route hypoglycemia in diabetes (FEEHD): “en-route” to invoke the possibility that patients with diabetes might crash if their blood sugar drops too low while driving in for a blood draw, he said at the annual meeting of the American Association of Clinical Endocrinologists.

The next step in Cape Girardeau was a prevention program to monitor blood glucose and adjust medications for patients with diabetes who were fasting for a test. It reduced the incidence of hypoglycemic events by 68%, with an even greater drop in the incidence of severe hypoglycemia below 50 mg/dL (Postgrad. Med. 2013;125:136-43).

“We’ve been trying to build a case” that FEEHD really is a problem, but there’s been some skepticism because “we are trying to change a deeply rooted tradition” and the notion that diabetics can fast just like anyone else. Even so, “people are coming around now that we have data,” Dr. Aldasouqi said. Currently at Michigan State, “my group is not ordering fasting” for lipid tests, although it remains routine in other clinics there. They opted for that approach, instead of reducing diabetes medications during fasts, because of the growing evidence that patients – whether they have diabetes or not – really don’t need to fast for lipid panels, he said (Circulation 2015;131:e471).

There was no external funding for the project. Dr. Aldasouqi is a speaker or adviser for Janssen, Sanofi, and Takeda.

[email protected]

NASHVILLE, TENN. – Neck circumferences at or above 36 cm in women and 39 cm in men might signal impending metabolic problems, according to researchers from the Medical University of Sofia, Bulgaria.

When patients have necks larger than that, “it is an argument to start more active preventative strategies because they will likely develop metabolic syndrome, if it’s not already present,” said investigator Dr. Zdravko Kamenov, an endocrinologist at the university.

The conclusion is based on a study of waist and neck circumference in 168 obese, hospitalized patients to see which better correlated with metabolic lab values. All the patients had a body mass index above 30 kg/m²; the average BMI was 35. About 70% of the participants were women, and patients with known diabetes, cancer, or chronic kidney or liver disease were excluded from the study.

Waist circumference is well accepted as a marker for abdominal fat and metabolic risk, but it can be difficult to measure and unreliable in obese people, and there are different opinions about where to place the measuring tape. Over the past few years, neck circumference has emerged as an easier alternative and has been associated with metabolic syndrome, obstructive sleep apnea, and heart disease when large.

“At this point, it’s probably better to measure both to increase the predictive value of anthropomorphic measurements,” Dr. Kamenov said at the annual meeting of the American Association of Clinical Endocrinologists.

Measuring both seems best because, in the study, waist circumference correlated better with plasma glucose problems, while neck circumference correlated better with other metabolic issues. Neck circumference also seemed to work better in women than in men, probably because of differences in neck musculature.

For instance, a neck circumference above 35.75 cm was the better predictor of dyslipidemia in women (odds ratio, 4.7; 95% confidence interval, 1.9-12.1,;P = .001). Neck circumference above 34.5 cm in women (OR 5.4; 95% CI 1.80-16.0; P = .003) and 38.75 cm in men (OR 24.6, 95% CI 1.5-398.1, P = 0.024) better predicted metabolic syndrome.

On the other hand, waist circumference over 100.5 cm was more predictive of type 2 diabetes in women (OR 3.2; 95% CI 1.1-9.4; P = .029). Waist circumference above 96.5 cm in women (OR 3.2; 95% CI 1.1-9.5; P = .033) and 101 cm in men was the better predictor of insulin resistance, with a sensitivity of 93% and specificity of 75% in men.

Waist circumference was taken at the midpoint between the inferior costal margin and the superior border of the iliac crest on the mid-axillary line. Neck circumference was measured between the mid-cervical spine and mid-anterior neck just below the laryngeal prominence.

To some extent, neck and waist circumference measure different things. While waist circumference measures visceral fat and to a lesser extent subcutaneous fat, neck circumference is largely a measure of subcutaneous upper body fat, which is important for the generation of the free fatty acids associated with metabolic syndrome, Dr. Kamenov said.

Patients were, on average, 52 years old; 41% turned had type 2 diabetes; 42% had prediabetes; and 87% had metabolic syndrome.

Dr. Kamenov has no disclosures, and there was no outside funding for the work.

[email protected]

NASHVILLE, TENN. – Neck circumferences at or above 36 cm in women and 39 cm in men might signal impending metabolic problems, according to researchers from the Medical University of Sofia, Bulgaria.

When patients have necks larger than that, “it is an argument to start more active preventative strategies because they will likely develop metabolic syndrome, if it’s not already present,” said investigator Dr. Zdravko Kamenov, an endocrinologist at the university.

The conclusion is based on a study of waist and neck circumference in 168 obese, hospitalized patients to see which better correlated with metabolic lab values. All the patients had a body mass index above 30 kg/m²; the average BMI was 35. About 70% of the participants were women, and patients with known diabetes, cancer, or chronic kidney or liver disease were excluded from the study.

Waist circumference is well accepted as a marker for abdominal fat and metabolic risk, but it can be difficult to measure and unreliable in obese people, and there are different opinions about where to place the measuring tape. Over the past few years, neck circumference has emerged as an easier alternative and has been associated with metabolic syndrome, obstructive sleep apnea, and heart disease when large.

“At this point, it’s probably better to measure both to increase the predictive value of anthropomorphic measurements,” Dr. Kamenov said at the annual meeting of the American Association of Clinical Endocrinologists.

Measuring both seems best because, in the study, waist circumference correlated better with plasma glucose problems, while neck circumference correlated better with other metabolic issues. Neck circumference also seemed to work better in women than in men, probably because of differences in neck musculature.

For instance, a neck circumference above 35.75 cm was the better predictor of dyslipidemia in women (odds ratio, 4.7; 95% confidence interval, 1.9-12.1,;P = .001). Neck circumference above 34.5 cm in women (OR 5.4; 95% CI 1.80-16.0; P = .003) and 38.75 cm in men (OR 24.6, 95% CI 1.5-398.1, P = 0.024) better predicted metabolic syndrome.

On the other hand, waist circumference over 100.5 cm was more predictive of type 2 diabetes in women (OR 3.2; 95% CI 1.1-9.4; P = .029). Waist circumference above 96.5 cm in women (OR 3.2; 95% CI 1.1-9.5; P = .033) and 101 cm in men was the better predictor of insulin resistance, with a sensitivity of 93% and specificity of 75% in men.

Waist circumference was taken at the midpoint between the inferior costal margin and the superior border of the iliac crest on the mid-axillary line. Neck circumference was measured between the mid-cervical spine and mid-anterior neck just below the laryngeal prominence.

To some extent, neck and waist circumference measure different things. While waist circumference measures visceral fat and to a lesser extent subcutaneous fat, neck circumference is largely a measure of subcutaneous upper body fat, which is important for the generation of the free fatty acids associated with metabolic syndrome, Dr. Kamenov said.

Patients were, on average, 52 years old; 41% turned had type 2 diabetes; 42% had prediabetes; and 87% had metabolic syndrome.

Dr. Kamenov has no disclosures, and there was no outside funding for the work.

[email protected]

NASHVILLE, TENN. – Neck circumferences at or above 36 cm in women and 39 cm in men might signal impending metabolic problems, according to researchers from the Medical University of Sofia, Bulgaria.

When patients have necks larger than that, “it is an argument to start more active preventative strategies because they will likely develop metabolic syndrome, if it’s not already present,” said investigator Dr. Zdravko Kamenov, an endocrinologist at the university.

The conclusion is based on a study of waist and neck circumference in 168 obese, hospitalized patients to see which better correlated with metabolic lab values. All the patients had a body mass index above 30 kg/m²; the average BMI was 35. About 70% of the participants were women, and patients with known diabetes, cancer, or chronic kidney or liver disease were excluded from the study.

Waist circumference is well accepted as a marker for abdominal fat and metabolic risk, but it can be difficult to measure and unreliable in obese people, and there are different opinions about where to place the measuring tape. Over the past few years, neck circumference has emerged as an easier alternative and has been associated with metabolic syndrome, obstructive sleep apnea, and heart disease when large.

“At this point, it’s probably better to measure both to increase the predictive value of anthropomorphic measurements,” Dr. Kamenov said at the annual meeting of the American Association of Clinical Endocrinologists.

Measuring both seems best because, in the study, waist circumference correlated better with plasma glucose problems, while neck circumference correlated better with other metabolic issues. Neck circumference also seemed to work better in women than in men, probably because of differences in neck musculature.

For instance, a neck circumference above 35.75 cm was the better predictor of dyslipidemia in women (odds ratio, 4.7; 95% confidence interval, 1.9-12.1,;P = .001). Neck circumference above 34.5 cm in women (OR 5.4; 95% CI 1.80-16.0; P = .003) and 38.75 cm in men (OR 24.6, 95% CI 1.5-398.1, P = 0.024) better predicted metabolic syndrome.

On the other hand, waist circumference over 100.5 cm was more predictive of type 2 diabetes in women (OR 3.2; 95% CI 1.1-9.4; P = .029). Waist circumference above 96.5 cm in women (OR 3.2; 95% CI 1.1-9.5; P = .033) and 101 cm in men was the better predictor of insulin resistance, with a sensitivity of 93% and specificity of 75% in men.

Waist circumference was taken at the midpoint between the inferior costal margin and the superior border of the iliac crest on the mid-axillary line. Neck circumference was measured between the mid-cervical spine and mid-anterior neck just below the laryngeal prominence.

To some extent, neck and waist circumference measure different things. While waist circumference measures visceral fat and to a lesser extent subcutaneous fat, neck circumference is largely a measure of subcutaneous upper body fat, which is important for the generation of the free fatty acids associated with metabolic syndrome, Dr. Kamenov said.

Patients were, on average, 52 years old; 41% turned had type 2 diabetes; 42% had prediabetes; and 87% had metabolic syndrome.

Dr. Kamenov has no disclosures, and there was no outside funding for the work.

[email protected]