M. Alexander Otto

SAN FRANCISCO – The sodium-glucose transporter 2 inhibitor (SGLT2) dapagliflozin (Farxiga) was better than placebo at slowing down kidney disease in patients with type 2 diabetes, and it showed reductions in the relative risk of renal-specific and cardiorenal outcomes of 47% and 24%, respectively, over 4 years, according to an analysis of the DECLARE-TIMI58 trial presented at the annual scientific sessions of the American Diabetes Association.

M. Alexander Otto

The findings add to a message physicians are hearing more and more frequently – that SGLT2 inhibitors, which also include empagliflozin (Jardiance) and canagliflozin (Invokana), could be useful for the early prevention of chronic kidney disease in patients who have type 2 diabetes. The main difference between the DECLARE-TIMI58 and previous study data was that most of its population did not have chronic kidney disease.

The drug should be given “at a very early stage of disease – it can reverse the disease and its complications [and] change the outcomes of patients,” said investigator Itamar Raz, MD, of Hebrew University, Jerusalem, in presenting the findings, which were published simultaneously in the Lancet Diabetes & Endocrinology (2019 Jun 10. doi: 10.1016/S2213-8587[19]30180-9).

What’s new in this renal analysis of DECLARE-TIMI58 is that patients were relatively healthy – 60% of them were without established cardiovascular disease and had much better renal function at baseline, compared with patients in other studies. About half of the patients started out with an estimated glomerular filtration rate (eGFR) more than 90 mL/min per 1.73 m², which means that they had normal kidney function, and most of the rest of the patients had normal to near-normal renal function or mild renal failure. Findings from previous trials with SGLT2 inhibitors that showed renal protection generally included patients with established cardiovascular disease who started out with greater kidney impairment.

Previous findings have also demonstrated cardioprotective effects with SGLT2 inhibitors in patients with type 2 diabetes. For instance, in earlier results from the DECLARE-TIMI58 trial, dapagliflozin reduced the frequency of cardiovascular death or hospitalization for heart failure, compared with placebo (4.9% vs. 5.8%, respectively; New Engl J Med. 2019;380:347-57), although it did not significantly reduce the frequency of stroke, heart attack, or all-cause death, unlike the results from glucagonlike peptide–1 receptor agonists in much sicker patients (Circulation. 2019;139[17]:2022-31).

Taken as a whole, Dr. Raz said that findings for SGLT2 inhibitors, which, like the glucagonlike peptide–1 receptor agonists, are indicated as second-line therapy in type 2 diabetes after metformin, suggest that they should be used sooner in type 2 disease, perhaps in patients with a hemoglobin A_1c level as low at 6.5%.

The absolute benefits of dapagliflozin, compared with placebo, notwithstanding, there are safety concerns with SGLT2s, including genitourinary infections, acute kidney injury, Fournier gangrene, diabetic ketoacidosis, bone fractures, and leg amputations (the latter two only with canagliflozin), many of which have been subject to warnings from the Food and Drug Administration.

Safety outcomes for dapagliflozin, compared with placebo, were not tabulated in the new renal report, but the authors noted a previously reported decrease of 30% in risk for acute kidney injury and major hypoglycemia with dapagliflozin over placebo. There was 1 case of Fournier gangrene with the drug versus 5 with placebo; 27 cases of diabetic ketoacidosis versus 12, respectively; 123 amputations versus 113; and 76 genital infections versus 9.

M. Alexander Otto

Matthew Riddle, MD, of Oregon Health and Science University, Portland, said SGLT2 studies “have shown important short-term benefit, but we have no information on long-term safety. These drugs are not physiologic; they do something powerful, but it’s nothing you see in nature. We don’t really know what they do yet; the physiology is still being worked out.”

DECLARE-TIMI58 randomized 8,582 patients with type 2 diabetes to receive dapagliflozin 10 mg orally daily and 8,578 patients to receive placebo. The patients remained on routine diabetes and cardiovascular care. Inclusion criteria included either established atherosclerotic cardiovascular disease (41% of patients) or cardiovascular risk factors (almost 60%), and creatinine clearance of at least 60 mL/min. Median follow-up was 4.2 years.

Overall, 4.2% of patients receiving dapagliflozin and 5.3% of those receiving placebo, met a prespecified secondary cardiorenal composite outcome of end-stage renal disease; death from renal or cardiovascular causes; or a decline of at least 40% in eGFR to less than 60 mL/min per 1.73 m² according to two tests at least 4 weeks apart (hazard ratio, 0.76; P less than .0001).

Similarly, 1.5% of dapagliflozin patients and 2.6% of those on placebo met a prespecified renal-specific composite of those factors minus death from cardiovascular causes (HR, 0.53; P less than .0001).

Among placebo-treated patients, 2.5% had a sustained decline in eGFR of at least 40% to less than 60 mL/min per 1.73 m², compared with 1.4% in the dapagliflozin group (HR, 0.54; P less than .0001). There were 11 cases of end-stage renal disease or renal death with dapagliflozin (0.1%), compared with 27 (0.3%) with placebo (HR, 0.41; P = .012).

Among patients who entered the trial with significant renal impairment – an eGFR of less than 60 mL/min per 1.73 m² – the difference in further renal decline with dapagliflozin was not statistically significant against placebo because of the small number of patients, but Dr. Raz said the drug should still be used earlier in type 2 disease.

Dapagliflozin patients fared worse on renal measurements at 6 months, but caught up by year 2, and surpassed placebo at years 3 and 4, the authors wrote in the latest report.

Just more than 60% of participants were men; patients were in their 60s, on average, and overweight. About 80% of the patients were white.

AstraZeneca, which makes dapagliflozin, was involved with study design, data collection, data analysis, interpretation, and writing of the report. Four authors were employees of the company, and all but two of the 17 others, including Dr. Raz, disclosed personal payments from the company and/or research funding. Dr. Riddle disclosed receiving research funding from AstraZeneca.
 

[email protected]

SAN FRANCISCO – The sodium-glucose transporter 2 inhibitor (SGLT2) dapagliflozin (Farxiga) was better than placebo at slowing down kidney disease in patients with type 2 diabetes, and it showed reductions in the relative risk of renal-specific and cardiorenal outcomes of 47% and 24%, respectively, over 4 years, according to an analysis of the DECLARE-TIMI58 trial presented at the annual scientific sessions of the American Diabetes Association.

M. Alexander Otto

The findings add to a message physicians are hearing more and more frequently – that SGLT2 inhibitors, which also include empagliflozin (Jardiance) and canagliflozin (Invokana), could be useful for the early prevention of chronic kidney disease in patients who have type 2 diabetes. The main difference between the DECLARE-TIMI58 and previous study data was that most of its population did not have chronic kidney disease.

The drug should be given “at a very early stage of disease – it can reverse the disease and its complications [and] change the outcomes of patients,” said investigator Itamar Raz, MD, of Hebrew University, Jerusalem, in presenting the findings, which were published simultaneously in the Lancet Diabetes & Endocrinology (2019 Jun 10. doi: 10.1016/S2213-8587[19]30180-9).

What’s new in this renal analysis of DECLARE-TIMI58 is that patients were relatively healthy – 60% of them were without established cardiovascular disease and had much better renal function at baseline, compared with patients in other studies. About half of the patients started out with an estimated glomerular filtration rate (eGFR) more than 90 mL/min per 1.73 m², which means that they had normal kidney function, and most of the rest of the patients had normal to near-normal renal function or mild renal failure. Findings from previous trials with SGLT2 inhibitors that showed renal protection generally included patients with established cardiovascular disease who started out with greater kidney impairment.

Previous findings have also demonstrated cardioprotective effects with SGLT2 inhibitors in patients with type 2 diabetes. For instance, in earlier results from the DECLARE-TIMI58 trial, dapagliflozin reduced the frequency of cardiovascular death or hospitalization for heart failure, compared with placebo (4.9% vs. 5.8%, respectively; New Engl J Med. 2019;380:347-57), although it did not significantly reduce the frequency of stroke, heart attack, or all-cause death, unlike the results from glucagonlike peptide–1 receptor agonists in much sicker patients (Circulation. 2019;139[17]:2022-31).

Taken as a whole, Dr. Raz said that findings for SGLT2 inhibitors, which, like the glucagonlike peptide–1 receptor agonists, are indicated as second-line therapy in type 2 diabetes after metformin, suggest that they should be used sooner in type 2 disease, perhaps in patients with a hemoglobin A_1c level as low at 6.5%.

The absolute benefits of dapagliflozin, compared with placebo, notwithstanding, there are safety concerns with SGLT2s, including genitourinary infections, acute kidney injury, Fournier gangrene, diabetic ketoacidosis, bone fractures, and leg amputations (the latter two only with canagliflozin), many of which have been subject to warnings from the Food and Drug Administration.

Safety outcomes for dapagliflozin, compared with placebo, were not tabulated in the new renal report, but the authors noted a previously reported decrease of 30% in risk for acute kidney injury and major hypoglycemia with dapagliflozin over placebo. There was 1 case of Fournier gangrene with the drug versus 5 with placebo; 27 cases of diabetic ketoacidosis versus 12, respectively; 123 amputations versus 113; and 76 genital infections versus 9.

M. Alexander Otto

Matthew Riddle, MD, of Oregon Health and Science University, Portland, said SGLT2 studies “have shown important short-term benefit, but we have no information on long-term safety. These drugs are not physiologic; they do something powerful, but it’s nothing you see in nature. We don’t really know what they do yet; the physiology is still being worked out.”

DECLARE-TIMI58 randomized 8,582 patients with type 2 diabetes to receive dapagliflozin 10 mg orally daily and 8,578 patients to receive placebo. The patients remained on routine diabetes and cardiovascular care. Inclusion criteria included either established atherosclerotic cardiovascular disease (41% of patients) or cardiovascular risk factors (almost 60%), and creatinine clearance of at least 60 mL/min. Median follow-up was 4.2 years.

Overall, 4.2% of patients receiving dapagliflozin and 5.3% of those receiving placebo, met a prespecified secondary cardiorenal composite outcome of end-stage renal disease; death from renal or cardiovascular causes; or a decline of at least 40% in eGFR to less than 60 mL/min per 1.73 m² according to two tests at least 4 weeks apart (hazard ratio, 0.76; P less than .0001).

Similarly, 1.5% of dapagliflozin patients and 2.6% of those on placebo met a prespecified renal-specific composite of those factors minus death from cardiovascular causes (HR, 0.53; P less than .0001).

Among placebo-treated patients, 2.5% had a sustained decline in eGFR of at least 40% to less than 60 mL/min per 1.73 m², compared with 1.4% in the dapagliflozin group (HR, 0.54; P less than .0001). There were 11 cases of end-stage renal disease or renal death with dapagliflozin (0.1%), compared with 27 (0.3%) with placebo (HR, 0.41; P = .012).

Among patients who entered the trial with significant renal impairment – an eGFR of less than 60 mL/min per 1.73 m² – the difference in further renal decline with dapagliflozin was not statistically significant against placebo because of the small number of patients, but Dr. Raz said the drug should still be used earlier in type 2 disease.

Dapagliflozin patients fared worse on renal measurements at 6 months, but caught up by year 2, and surpassed placebo at years 3 and 4, the authors wrote in the latest report.

Just more than 60% of participants were men; patients were in their 60s, on average, and overweight. About 80% of the patients were white.

AstraZeneca, which makes dapagliflozin, was involved with study design, data collection, data analysis, interpretation, and writing of the report. Four authors were employees of the company, and all but two of the 17 others, including Dr. Raz, disclosed personal payments from the company and/or research funding. Dr. Riddle disclosed receiving research funding from AstraZeneca.
 

[email protected]

SAN FRANCISCO – The sodium-glucose transporter 2 inhibitor (SGLT2) dapagliflozin (Farxiga) was better than placebo at slowing down kidney disease in patients with type 2 diabetes, and it showed reductions in the relative risk of renal-specific and cardiorenal outcomes of 47% and 24%, respectively, over 4 years, according to an analysis of the DECLARE-TIMI58 trial presented at the annual scientific sessions of the American Diabetes Association.

M. Alexander Otto

The findings add to a message physicians are hearing more and more frequently – that SGLT2 inhibitors, which also include empagliflozin (Jardiance) and canagliflozin (Invokana), could be useful for the early prevention of chronic kidney disease in patients who have type 2 diabetes. The main difference between the DECLARE-TIMI58 and previous study data was that most of its population did not have chronic kidney disease.

The drug should be given “at a very early stage of disease – it can reverse the disease and its complications [and] change the outcomes of patients,” said investigator Itamar Raz, MD, of Hebrew University, Jerusalem, in presenting the findings, which were published simultaneously in the Lancet Diabetes & Endocrinology (2019 Jun 10. doi: 10.1016/S2213-8587[19]30180-9).

What’s new in this renal analysis of DECLARE-TIMI58 is that patients were relatively healthy – 60% of them were without established cardiovascular disease and had much better renal function at baseline, compared with patients in other studies. About half of the patients started out with an estimated glomerular filtration rate (eGFR) more than 90 mL/min per 1.73 m², which means that they had normal kidney function, and most of the rest of the patients had normal to near-normal renal function or mild renal failure. Findings from previous trials with SGLT2 inhibitors that showed renal protection generally included patients with established cardiovascular disease who started out with greater kidney impairment.

Previous findings have also demonstrated cardioprotective effects with SGLT2 inhibitors in patients with type 2 diabetes. For instance, in earlier results from the DECLARE-TIMI58 trial, dapagliflozin reduced the frequency of cardiovascular death or hospitalization for heart failure, compared with placebo (4.9% vs. 5.8%, respectively; New Engl J Med. 2019;380:347-57), although it did not significantly reduce the frequency of stroke, heart attack, or all-cause death, unlike the results from glucagonlike peptide–1 receptor agonists in much sicker patients (Circulation. 2019;139[17]:2022-31).

Taken as a whole, Dr. Raz said that findings for SGLT2 inhibitors, which, like the glucagonlike peptide–1 receptor agonists, are indicated as second-line therapy in type 2 diabetes after metformin, suggest that they should be used sooner in type 2 disease, perhaps in patients with a hemoglobin A_1c level as low at 6.5%.

The absolute benefits of dapagliflozin, compared with placebo, notwithstanding, there are safety concerns with SGLT2s, including genitourinary infections, acute kidney injury, Fournier gangrene, diabetic ketoacidosis, bone fractures, and leg amputations (the latter two only with canagliflozin), many of which have been subject to warnings from the Food and Drug Administration.

Safety outcomes for dapagliflozin, compared with placebo, were not tabulated in the new renal report, but the authors noted a previously reported decrease of 30% in risk for acute kidney injury and major hypoglycemia with dapagliflozin over placebo. There was 1 case of Fournier gangrene with the drug versus 5 with placebo; 27 cases of diabetic ketoacidosis versus 12, respectively; 123 amputations versus 113; and 76 genital infections versus 9.

M. Alexander Otto

Matthew Riddle, MD, of Oregon Health and Science University, Portland, said SGLT2 studies “have shown important short-term benefit, but we have no information on long-term safety. These drugs are not physiologic; they do something powerful, but it’s nothing you see in nature. We don’t really know what they do yet; the physiology is still being worked out.”

DECLARE-TIMI58 randomized 8,582 patients with type 2 diabetes to receive dapagliflozin 10 mg orally daily and 8,578 patients to receive placebo. The patients remained on routine diabetes and cardiovascular care. Inclusion criteria included either established atherosclerotic cardiovascular disease (41% of patients) or cardiovascular risk factors (almost 60%), and creatinine clearance of at least 60 mL/min. Median follow-up was 4.2 years.

Overall, 4.2% of patients receiving dapagliflozin and 5.3% of those receiving placebo, met a prespecified secondary cardiorenal composite outcome of end-stage renal disease; death from renal or cardiovascular causes; or a decline of at least 40% in eGFR to less than 60 mL/min per 1.73 m² according to two tests at least 4 weeks apart (hazard ratio, 0.76; P less than .0001).

Similarly, 1.5% of dapagliflozin patients and 2.6% of those on placebo met a prespecified renal-specific composite of those factors minus death from cardiovascular causes (HR, 0.53; P less than .0001).

Among placebo-treated patients, 2.5% had a sustained decline in eGFR of at least 40% to less than 60 mL/min per 1.73 m², compared with 1.4% in the dapagliflozin group (HR, 0.54; P less than .0001). There were 11 cases of end-stage renal disease or renal death with dapagliflozin (0.1%), compared with 27 (0.3%) with placebo (HR, 0.41; P = .012).

Among patients who entered the trial with significant renal impairment – an eGFR of less than 60 mL/min per 1.73 m² – the difference in further renal decline with dapagliflozin was not statistically significant against placebo because of the small number of patients, but Dr. Raz said the drug should still be used earlier in type 2 disease.

Dapagliflozin patients fared worse on renal measurements at 6 months, but caught up by year 2, and surpassed placebo at years 3 and 4, the authors wrote in the latest report.

Just more than 60% of participants were men; patients were in their 60s, on average, and overweight. About 80% of the patients were white.

AstraZeneca, which makes dapagliflozin, was involved with study design, data collection, data analysis, interpretation, and writing of the report. Four authors were employees of the company, and all but two of the 17 others, including Dr. Raz, disclosed personal payments from the company and/or research funding. Dr. Riddle disclosed receiving research funding from AstraZeneca.
 

[email protected]

SAN FRANCISCO – The dipeptidyl peptidase-4 inhibitor linagliptin (Tradjenta) is safe on the kidneys, the cardiovascular system, and in older people with type 2 diabetes, according to findings presented at the annual scientific sessions of the American Diabetes Association.

Alex Otto/MDedge News

Investigators in the international Cardiovascular and Renal Microvascular Outcome Study with Linagliptin (CARMELINA) randomized 6,979 patients with type 2 diabetes who also had cardiovascular and/or kidney disease 1:1 to daily oral linagliptin 5 mg or placebo on top of standard of care, and they followed them for a median of 2.2 years. The mean age was 65.9 years, baseline hemoglobin A_1c was 8.0%, and disease duration was about 15 years. Almost 63% of the patients were men, and about a quarter had a history of heart failure at baseline (JAMA. 2019;321[1]:69-79).

The study was unusual among other DPP-4 trials in that almost 60% of the patients were older than 65 years and 62.3% had impaired renal function with an estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m².

There was no increased risk with linagliptin, compared with placebo, in the primary composite outcome of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction (12.4% vs. 12.1%, respectively; hazard ratio, 1.02; P = .74), and there was no difference between the individual components even when broken down by age (younger than 65, 65-75, or older than 75 years) or by renal function (eGFR 60 or more, 45 to less than 60, 30 to less than 45, or less than 30 ml/min per 1.73 m^2), according to investigator Mark Cooper, MBBS, PhD, of the department of diabetes at Monash University, Melbourne, who presented the findings.

There was no increase in the number of hospitalizations for heart failure with linagliptin, compared with placebo (6% vs. 6.5%, respectively; HR, 0.90; P = .26) – a concern with some DPP-4 inhibitors – and no increase in hypoglycemia (just over a quarter in both groups), even when broken down by age and renal function.

A decrease in albuminuria with linagliptin held across all renal subgroups. It is not known if that was because of glucose lowering or some other effect, but Dr. Cooper said he believed there was “a modest renal protective effect, [although] not at the level one would expect to translate into hard renal outcomes.”

M. Alexander Otto/MDedge News

Robert Eckel, MD, a professor of medicine at the University of Colorado at Denver, Aurora, who moderated the session, said the results were reassuring. “Ultimately, linagliptin seems safe,” even in older people with reduced eGFR. “It does not improve cardiovascular outcomes, but based on many DPP-4 trials, we didn’t expect it to,” he said.

“I don’t think DPP-4s are going to fall into any different place in the [treatment] algorithm” based on these results, he added. The class is currently third-line after metformin or insulin, followed by sodium-glucose cotransporter 2 inhibitors or glucagonlike peptide–1 receptor agonists for cardiovascular protection.

“When we look at [cardiovascular outcomes], ultimately, the SGLT2 inhibitors and the GLP-1 receptor agonists win,” he said. In addition, the blood glucose effects of linagliptin are “pretty modest, so if lowering hemoglobin A_1c is the focus, this drug would be lower down on the list.”

Overall, linagliptin “falls into a lesser class, but a safe class for certain circumstances,” said Dr. Eckel, who gave the example of a woman in her late 70s with moderate to severe kidney function, an HbA_1c level of 7.9%, and no cardiovascular disease. Her HbA1c might get down to 7.6% or so with linagliptin, he said, “but I’m not sure we have absolute proof of the benefit” of such a modest decline.

Boehringer Ingelheim, the maker of linagliptin, funded the study. The presenter disclosed honoraria, speaking fees, and grants from the company. A number of the investigators were employees of the company.

SAN FRANCISCO – The dipeptidyl peptidase-4 inhibitor linagliptin (Tradjenta) is safe on the kidneys, the cardiovascular system, and in older people with type 2 diabetes, according to findings presented at the annual scientific sessions of the American Diabetes Association.

Alex Otto/MDedge News

Investigators in the international Cardiovascular and Renal Microvascular Outcome Study with Linagliptin (CARMELINA) randomized 6,979 patients with type 2 diabetes who also had cardiovascular and/or kidney disease 1:1 to daily oral linagliptin 5 mg or placebo on top of standard of care, and they followed them for a median of 2.2 years. The mean age was 65.9 years, baseline hemoglobin A_1c was 8.0%, and disease duration was about 15 years. Almost 63% of the patients were men, and about a quarter had a history of heart failure at baseline (JAMA. 2019;321[1]:69-79).

The study was unusual among other DPP-4 trials in that almost 60% of the patients were older than 65 years and 62.3% had impaired renal function with an estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m².

There was no increased risk with linagliptin, compared with placebo, in the primary composite outcome of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction (12.4% vs. 12.1%, respectively; hazard ratio, 1.02; P = .74), and there was no difference between the individual components even when broken down by age (younger than 65, 65-75, or older than 75 years) or by renal function (eGFR 60 or more, 45 to less than 60, 30 to less than 45, or less than 30 ml/min per 1.73 m^2), according to investigator Mark Cooper, MBBS, PhD, of the department of diabetes at Monash University, Melbourne, who presented the findings.

There was no increase in the number of hospitalizations for heart failure with linagliptin, compared with placebo (6% vs. 6.5%, respectively; HR, 0.90; P = .26) – a concern with some DPP-4 inhibitors – and no increase in hypoglycemia (just over a quarter in both groups), even when broken down by age and renal function.

A decrease in albuminuria with linagliptin held across all renal subgroups. It is not known if that was because of glucose lowering or some other effect, but Dr. Cooper said he believed there was “a modest renal protective effect, [although] not at the level one would expect to translate into hard renal outcomes.”

M. Alexander Otto/MDedge News

Robert Eckel, MD, a professor of medicine at the University of Colorado at Denver, Aurora, who moderated the session, said the results were reassuring. “Ultimately, linagliptin seems safe,” even in older people with reduced eGFR. “It does not improve cardiovascular outcomes, but based on many DPP-4 trials, we didn’t expect it to,” he said.

“I don’t think DPP-4s are going to fall into any different place in the [treatment] algorithm” based on these results, he added. The class is currently third-line after metformin or insulin, followed by sodium-glucose cotransporter 2 inhibitors or glucagonlike peptide–1 receptor agonists for cardiovascular protection.

“When we look at [cardiovascular outcomes], ultimately, the SGLT2 inhibitors and the GLP-1 receptor agonists win,” he said. In addition, the blood glucose effects of linagliptin are “pretty modest, so if lowering hemoglobin A_1c is the focus, this drug would be lower down on the list.”

Overall, linagliptin “falls into a lesser class, but a safe class for certain circumstances,” said Dr. Eckel, who gave the example of a woman in her late 70s with moderate to severe kidney function, an HbA_1c level of 7.9%, and no cardiovascular disease. Her HbA1c might get down to 7.6% or so with linagliptin, he said, “but I’m not sure we have absolute proof of the benefit” of such a modest decline.

Boehringer Ingelheim, the maker of linagliptin, funded the study. The presenter disclosed honoraria, speaking fees, and grants from the company. A number of the investigators were employees of the company.

SAN FRANCISCO – The dipeptidyl peptidase-4 inhibitor linagliptin (Tradjenta) is safe on the kidneys, the cardiovascular system, and in older people with type 2 diabetes, according to findings presented at the annual scientific sessions of the American Diabetes Association.

Alex Otto/MDedge News

Investigators in the international Cardiovascular and Renal Microvascular Outcome Study with Linagliptin (CARMELINA) randomized 6,979 patients with type 2 diabetes who also had cardiovascular and/or kidney disease 1:1 to daily oral linagliptin 5 mg or placebo on top of standard of care, and they followed them for a median of 2.2 years. The mean age was 65.9 years, baseline hemoglobin A_1c was 8.0%, and disease duration was about 15 years. Almost 63% of the patients were men, and about a quarter had a history of heart failure at baseline (JAMA. 2019;321[1]:69-79).

The study was unusual among other DPP-4 trials in that almost 60% of the patients were older than 65 years and 62.3% had impaired renal function with an estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m².

There was no increased risk with linagliptin, compared with placebo, in the primary composite outcome of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction (12.4% vs. 12.1%, respectively; hazard ratio, 1.02; P = .74), and there was no difference between the individual components even when broken down by age (younger than 65, 65-75, or older than 75 years) or by renal function (eGFR 60 or more, 45 to less than 60, 30 to less than 45, or less than 30 ml/min per 1.73 m^2), according to investigator Mark Cooper, MBBS, PhD, of the department of diabetes at Monash University, Melbourne, who presented the findings.

There was no increase in the number of hospitalizations for heart failure with linagliptin, compared with placebo (6% vs. 6.5%, respectively; HR, 0.90; P = .26) – a concern with some DPP-4 inhibitors – and no increase in hypoglycemia (just over a quarter in both groups), even when broken down by age and renal function.

A decrease in albuminuria with linagliptin held across all renal subgroups. It is not known if that was because of glucose lowering or some other effect, but Dr. Cooper said he believed there was “a modest renal protective effect, [although] not at the level one would expect to translate into hard renal outcomes.”

M. Alexander Otto/MDedge News

Robert Eckel, MD, a professor of medicine at the University of Colorado at Denver, Aurora, who moderated the session, said the results were reassuring. “Ultimately, linagliptin seems safe,” even in older people with reduced eGFR. “It does not improve cardiovascular outcomes, but based on many DPP-4 trials, we didn’t expect it to,” he said.

“I don’t think DPP-4s are going to fall into any different place in the [treatment] algorithm” based on these results, he added. The class is currently third-line after metformin or insulin, followed by sodium-glucose cotransporter 2 inhibitors or glucagonlike peptide–1 receptor agonists for cardiovascular protection.

“When we look at [cardiovascular outcomes], ultimately, the SGLT2 inhibitors and the GLP-1 receptor agonists win,” he said. In addition, the blood glucose effects of linagliptin are “pretty modest, so if lowering hemoglobin A_1c is the focus, this drug would be lower down on the list.”

Overall, linagliptin “falls into a lesser class, but a safe class for certain circumstances,” said Dr. Eckel, who gave the example of a woman in her late 70s with moderate to severe kidney function, an HbA_1c level of 7.9%, and no cardiovascular disease. Her HbA1c might get down to 7.6% or so with linagliptin, he said, “but I’m not sure we have absolute proof of the benefit” of such a modest decline.

Boehringer Ingelheim, the maker of linagliptin, funded the study. The presenter disclosed honoraria, speaking fees, and grants from the company. A number of the investigators were employees of the company.

SAN FRANCISCO – Just a single risk factor for type 2 diabetes warrants screening for the disease in black and Hispanic adults, regardless of their body mass index, according to findings presented at the annual scientific sessions of the American Diabetes Association.

M. Alexander Otto/MDedge News

The conclusions come from a review of 5,656 participants aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective cohort study. The participants had no signs of cardiovascular disease at enrollment.

The goal of the study reported at the meeting was to see if current ADA screening guidelines are appropriate across racial groups in an increasingly diverse United States. The guidelines recommend body mass index (BMI) as a trigger for screening for type 2 diabetes. The current advice is to screen any adult who has a BMI at or above 25 kg/m² (23 kg/m² for Asian Americans) and at least one risk factor for type 2 diabetes, such as hypertension, dyslipidemia, or physical inactivity.

Being black, Asian American, Hispanic, Pacific Islander, or American Indian is itself a risk factor, so “someone from a minority group just needs to meet the BMI criteria,” said lead investigator Luis Rodriguez, a PhD candidate in epidemiology at the University of California, San Francisco.

He and his colleagues focused on 2,383 white, 653 Chinese American, 1,459 black, and 1,161 Hispanic participants in MESA who did not have type 2 diabetes at baseline. Participants were in their early 60s at baseline, on average, and just more than half of them were women. They had five medical exams between 2000 and 2012. The investigators calculated the BMI at which each group hit a 10% risk of developing diabetes within the next 10 years.

In general, the lines crossed at a BMI of about 23 kg/m² for Chinese Americans; 25 kg/m² for black and Hispanic participants; and 27 kg/m² for white participants, which is consistent with ADA advice. The guideline cut points are “appropriate for population-based screening where you may not know if the person in front of you has any diabetes risk factors,” Mr. Rodriguez said.

With known risk factors, however, BMI didn’t hold up. Black participants with one or more risk factor hit the 10% mark at a BMI of 24.7 kg/m^2, Hispanics at 23.8 kg/m^2, and Chinese Americans at 21.7 kg/m², all of which are below the recommended cut-points.

“Almost 80%-90% of participants” in minority groups “who had one or more risk factors were above the 10% threshold, so if they have at least one factor, they should pretty much be screened for diabetes, regardless of BMI,” he said.

The 25-kg/m² threshold worked for white participants; the investigators found that with one or more risk factors, white participants crossed the 10% line at a BMI of 26.2 kg/m². In addition, white participants with no diabetes risk factors crossed the 10% mark at around a BMI of 30 kg/m², which the investigators suggested as an appropriate screening trigger.

Participants were in their early 60s at baseline, on average, and just more than half of them were women. In all, 696 cases of type 2 diabetes were diagnosed over a median follow-up of about 9 years, which translated to an incidence rate of 11 cases per 1,000 person-years in white participants, 16 cases for Chinese Americans, 21 for black participants, and 22 for Hispanic participants. Well over half of the participants were overweight or obese at baseline, including about 80% of black and Hispanic participants.

The sample size reported in the abstract was smaller than that in the final presentation because the investigators did not adjust for diet in the final presentation, Mr. Rodriguez explained. Because some study participants did not report diet, by excluding diet from the model adjustment, the number of participants increased, as reflected in this text. Adjusting for diet did not alter the findings.

The National Heart, Lung, and Blood Institute sponsors MESA. Mr. Rodriguez was supported by a grant from the National Institutes of Health/National Institute of Diabetes and Kidney Disease. The other investigators reported having no disclosures.
 

[email protected]

SOURCE: Rodriguez L et al. ADA 2019, Abstract 115-OR.

SAN FRANCISCO – Just a single risk factor for type 2 diabetes warrants screening for the disease in black and Hispanic adults, regardless of their body mass index, according to findings presented at the annual scientific sessions of the American Diabetes Association.

M. Alexander Otto/MDedge News

The conclusions come from a review of 5,656 participants aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective cohort study. The participants had no signs of cardiovascular disease at enrollment.

The goal of the study reported at the meeting was to see if current ADA screening guidelines are appropriate across racial groups in an increasingly diverse United States. The guidelines recommend body mass index (BMI) as a trigger for screening for type 2 diabetes. The current advice is to screen any adult who has a BMI at or above 25 kg/m² (23 kg/m² for Asian Americans) and at least one risk factor for type 2 diabetes, such as hypertension, dyslipidemia, or physical inactivity.

Being black, Asian American, Hispanic, Pacific Islander, or American Indian is itself a risk factor, so “someone from a minority group just needs to meet the BMI criteria,” said lead investigator Luis Rodriguez, a PhD candidate in epidemiology at the University of California, San Francisco.

He and his colleagues focused on 2,383 white, 653 Chinese American, 1,459 black, and 1,161 Hispanic participants in MESA who did not have type 2 diabetes at baseline. Participants were in their early 60s at baseline, on average, and just more than half of them were women. They had five medical exams between 2000 and 2012. The investigators calculated the BMI at which each group hit a 10% risk of developing diabetes within the next 10 years.

In general, the lines crossed at a BMI of about 23 kg/m² for Chinese Americans; 25 kg/m² for black and Hispanic participants; and 27 kg/m² for white participants, which is consistent with ADA advice. The guideline cut points are “appropriate for population-based screening where you may not know if the person in front of you has any diabetes risk factors,” Mr. Rodriguez said.

With known risk factors, however, BMI didn’t hold up. Black participants with one or more risk factor hit the 10% mark at a BMI of 24.7 kg/m^2, Hispanics at 23.8 kg/m^2, and Chinese Americans at 21.7 kg/m², all of which are below the recommended cut-points.

“Almost 80%-90% of participants” in minority groups “who had one or more risk factors were above the 10% threshold, so if they have at least one factor, they should pretty much be screened for diabetes, regardless of BMI,” he said.

The 25-kg/m² threshold worked for white participants; the investigators found that with one or more risk factors, white participants crossed the 10% line at a BMI of 26.2 kg/m². In addition, white participants with no diabetes risk factors crossed the 10% mark at around a BMI of 30 kg/m², which the investigators suggested as an appropriate screening trigger.

Participants were in their early 60s at baseline, on average, and just more than half of them were women. In all, 696 cases of type 2 diabetes were diagnosed over a median follow-up of about 9 years, which translated to an incidence rate of 11 cases per 1,000 person-years in white participants, 16 cases for Chinese Americans, 21 for black participants, and 22 for Hispanic participants. Well over half of the participants were overweight or obese at baseline, including about 80% of black and Hispanic participants.

The sample size reported in the abstract was smaller than that in the final presentation because the investigators did not adjust for diet in the final presentation, Mr. Rodriguez explained. Because some study participants did not report diet, by excluding diet from the model adjustment, the number of participants increased, as reflected in this text. Adjusting for diet did not alter the findings.

The National Heart, Lung, and Blood Institute sponsors MESA. Mr. Rodriguez was supported by a grant from the National Institutes of Health/National Institute of Diabetes and Kidney Disease. The other investigators reported having no disclosures.
 

[email protected]

SOURCE: Rodriguez L et al. ADA 2019, Abstract 115-OR.

SAN FRANCISCO – Just a single risk factor for type 2 diabetes warrants screening for the disease in black and Hispanic adults, regardless of their body mass index, according to findings presented at the annual scientific sessions of the American Diabetes Association.

M. Alexander Otto/MDedge News

The conclusions come from a review of 5,656 participants aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective cohort study. The participants had no signs of cardiovascular disease at enrollment.

The goal of the study reported at the meeting was to see if current ADA screening guidelines are appropriate across racial groups in an increasingly diverse United States. The guidelines recommend body mass index (BMI) as a trigger for screening for type 2 diabetes. The current advice is to screen any adult who has a BMI at or above 25 kg/m² (23 kg/m² for Asian Americans) and at least one risk factor for type 2 diabetes, such as hypertension, dyslipidemia, or physical inactivity.

Being black, Asian American, Hispanic, Pacific Islander, or American Indian is itself a risk factor, so “someone from a minority group just needs to meet the BMI criteria,” said lead investigator Luis Rodriguez, a PhD candidate in epidemiology at the University of California, San Francisco.

He and his colleagues focused on 2,383 white, 653 Chinese American, 1,459 black, and 1,161 Hispanic participants in MESA who did not have type 2 diabetes at baseline. Participants were in their early 60s at baseline, on average, and just more than half of them were women. They had five medical exams between 2000 and 2012. The investigators calculated the BMI at which each group hit a 10% risk of developing diabetes within the next 10 years.

In general, the lines crossed at a BMI of about 23 kg/m² for Chinese Americans; 25 kg/m² for black and Hispanic participants; and 27 kg/m² for white participants, which is consistent with ADA advice. The guideline cut points are “appropriate for population-based screening where you may not know if the person in front of you has any diabetes risk factors,” Mr. Rodriguez said.

With known risk factors, however, BMI didn’t hold up. Black participants with one or more risk factor hit the 10% mark at a BMI of 24.7 kg/m^2, Hispanics at 23.8 kg/m^2, and Chinese Americans at 21.7 kg/m², all of which are below the recommended cut-points.

“Almost 80%-90% of participants” in minority groups “who had one or more risk factors were above the 10% threshold, so if they have at least one factor, they should pretty much be screened for diabetes, regardless of BMI,” he said.

The 25-kg/m² threshold worked for white participants; the investigators found that with one or more risk factors, white participants crossed the 10% line at a BMI of 26.2 kg/m². In addition, white participants with no diabetes risk factors crossed the 10% mark at around a BMI of 30 kg/m², which the investigators suggested as an appropriate screening trigger.

Participants were in their early 60s at baseline, on average, and just more than half of them were women. In all, 696 cases of type 2 diabetes were diagnosed over a median follow-up of about 9 years, which translated to an incidence rate of 11 cases per 1,000 person-years in white participants, 16 cases for Chinese Americans, 21 for black participants, and 22 for Hispanic participants. Well over half of the participants were overweight or obese at baseline, including about 80% of black and Hispanic participants.

The sample size reported in the abstract was smaller than that in the final presentation because the investigators did not adjust for diet in the final presentation, Mr. Rodriguez explained. Because some study participants did not report diet, by excluding diet from the model adjustment, the number of participants increased, as reflected in this text. Adjusting for diet did not alter the findings.

The National Heart, Lung, and Blood Institute sponsors MESA. Mr. Rodriguez was supported by a grant from the National Institutes of Health/National Institute of Diabetes and Kidney Disease. The other investigators reported having no disclosures.
 

[email protected]

SOURCE: Rodriguez L et al. ADA 2019, Abstract 115-OR.

SAN FRANCISCO – Switching cheese out of the diet for yogurt or reduced-fat milk was associated with a 16% reduction in risk for type 2 diabetes in a review of almost 200,000 participants presented at the annual scientific sessions at the American Diabetes Association.

M. Alexander Otto/MDedge News

Increasing yogurt consumption was also independently associated with a moderately lower risk of type 2 diabetes, and increasing cheese consumption with a moderately higher risk.

It might have been that yogurt and low-fat milk were simply indicators of healthier living and that cheese consumption – in the study, most commonly on pizza or as processed slices on cheeseburgers – indicated a less healthy way of life, but “we tried our best to control for confounders,” said study lead Jean-Philippe Drouin-Chartier, PhD, of the Harvard School of Public Health, Boston.

And it is possible, he said, that lactic acid bacteria in yogurt could have some effect on the gut microbiome that protects against type 2 disease.

Total dairy consumption has not changed much over the past few decades, but people are drinking less milk and eating more cheese and yogurt. Dr. Drouin-Chartier and colleagues wondered how that affected the risk of type 2 diabetes.

The investigators correlated changes in dairy consumption during 4-year intervals with the incidence of type 2 diabetes in subsequent 4-year intervals using three large, prospective cohort studies that all started about 30 years ago: the Health Professionals Follow-Up Study, Nurses’ Health Study I, and Nurses’ Health Study II.

There were almost 200,000 participants in the pooled analysis, with 2.9 million person-years of follow-up and 12,007 new cases of type 2 diabetes. Participants completed food-frequency questionnaires every 4 years. About 82% of the participants were women. At baseline, they reported consuming about one to four servings of dairy a day.

After adjustment for race, body mass index, calorie intake, family history, physical activity, and other factors associated with type 2 diabetes, the investigators found that increasing yogurt intake by one 4-ounce serving a day while decreasing cheese intake by one 1-ounce serving a day was associated with a 16% (95% confidence interval, 10%-22%) reduction in subsequent risk of type 2 disease. There was an 11% (95% CI, 7%-15%) reduction in risk when a cheese serving was subbed out for a daily 8-ounce serving of reduced-fat milk.

An extra 2 ounces of yogurt a day was associated with a 13% (95% CI, 6%-19%) lower risk of type 2 diabetes, compared with stable consumption, while an extra half ounce of cheese was associated with an 8% (95% CI, 2%-16%) increase in risk.

Overall, substitution of low-fat products (such as 0%-2% milk and low-fat cheese, yogurt, or sherbet) for high-fat products (such as whole milk, ice cream, and high-fat cheese) was associated with a 4% decrease in risk (hazard ratio, 0.96; 95% CI, 0.93-0.99).

However, substitution of reduced-fat milk for whole milk or low-fat cheese for high-fat cheese did not influence the risk, possibly because there is actually not much difference in fat content, Dr. Drouin-Chartier said.

The National Institutes of Health funded the study. Dr. Drouin-Chartier has served as a speaker and consultant for Dairy Farmers of Canada, one other author has advised the group, another has advised the U.S. Department of Agriculture, and the remaining authors had no disclosures.

SOURCE: Drouin-Chartier J et al. ADA 2019, Abstract 159-OR.

SAN FRANCISCO – Switching cheese out of the diet for yogurt or reduced-fat milk was associated with a 16% reduction in risk for type 2 diabetes in a review of almost 200,000 participants presented at the annual scientific sessions at the American Diabetes Association.

M. Alexander Otto/MDedge News

Increasing yogurt consumption was also independently associated with a moderately lower risk of type 2 diabetes, and increasing cheese consumption with a moderately higher risk.

It might have been that yogurt and low-fat milk were simply indicators of healthier living and that cheese consumption – in the study, most commonly on pizza or as processed slices on cheeseburgers – indicated a less healthy way of life, but “we tried our best to control for confounders,” said study lead Jean-Philippe Drouin-Chartier, PhD, of the Harvard School of Public Health, Boston.

And it is possible, he said, that lactic acid bacteria in yogurt could have some effect on the gut microbiome that protects against type 2 disease.

Total dairy consumption has not changed much over the past few decades, but people are drinking less milk and eating more cheese and yogurt. Dr. Drouin-Chartier and colleagues wondered how that affected the risk of type 2 diabetes.

The investigators correlated changes in dairy consumption during 4-year intervals with the incidence of type 2 diabetes in subsequent 4-year intervals using three large, prospective cohort studies that all started about 30 years ago: the Health Professionals Follow-Up Study, Nurses’ Health Study I, and Nurses’ Health Study II.

There were almost 200,000 participants in the pooled analysis, with 2.9 million person-years of follow-up and 12,007 new cases of type 2 diabetes. Participants completed food-frequency questionnaires every 4 years. About 82% of the participants were women. At baseline, they reported consuming about one to four servings of dairy a day.

After adjustment for race, body mass index, calorie intake, family history, physical activity, and other factors associated with type 2 diabetes, the investigators found that increasing yogurt intake by one 4-ounce serving a day while decreasing cheese intake by one 1-ounce serving a day was associated with a 16% (95% confidence interval, 10%-22%) reduction in subsequent risk of type 2 disease. There was an 11% (95% CI, 7%-15%) reduction in risk when a cheese serving was subbed out for a daily 8-ounce serving of reduced-fat milk.

An extra 2 ounces of yogurt a day was associated with a 13% (95% CI, 6%-19%) lower risk of type 2 diabetes, compared with stable consumption, while an extra half ounce of cheese was associated with an 8% (95% CI, 2%-16%) increase in risk.

Overall, substitution of low-fat products (such as 0%-2% milk and low-fat cheese, yogurt, or sherbet) for high-fat products (such as whole milk, ice cream, and high-fat cheese) was associated with a 4% decrease in risk (hazard ratio, 0.96; 95% CI, 0.93-0.99).

However, substitution of reduced-fat milk for whole milk or low-fat cheese for high-fat cheese did not influence the risk, possibly because there is actually not much difference in fat content, Dr. Drouin-Chartier said.

The National Institutes of Health funded the study. Dr. Drouin-Chartier has served as a speaker and consultant for Dairy Farmers of Canada, one other author has advised the group, another has advised the U.S. Department of Agriculture, and the remaining authors had no disclosures.

SOURCE: Drouin-Chartier J et al. ADA 2019, Abstract 159-OR.

SAN FRANCISCO – Switching cheese out of the diet for yogurt or reduced-fat milk was associated with a 16% reduction in risk for type 2 diabetes in a review of almost 200,000 participants presented at the annual scientific sessions at the American Diabetes Association.

M. Alexander Otto/MDedge News

Increasing yogurt consumption was also independently associated with a moderately lower risk of type 2 diabetes, and increasing cheese consumption with a moderately higher risk.

It might have been that yogurt and low-fat milk were simply indicators of healthier living and that cheese consumption – in the study, most commonly on pizza or as processed slices on cheeseburgers – indicated a less healthy way of life, but “we tried our best to control for confounders,” said study lead Jean-Philippe Drouin-Chartier, PhD, of the Harvard School of Public Health, Boston.

And it is possible, he said, that lactic acid bacteria in yogurt could have some effect on the gut microbiome that protects against type 2 disease.

Total dairy consumption has not changed much over the past few decades, but people are drinking less milk and eating more cheese and yogurt. Dr. Drouin-Chartier and colleagues wondered how that affected the risk of type 2 diabetes.

The investigators correlated changes in dairy consumption during 4-year intervals with the incidence of type 2 diabetes in subsequent 4-year intervals using three large, prospective cohort studies that all started about 30 years ago: the Health Professionals Follow-Up Study, Nurses’ Health Study I, and Nurses’ Health Study II.

There were almost 200,000 participants in the pooled analysis, with 2.9 million person-years of follow-up and 12,007 new cases of type 2 diabetes. Participants completed food-frequency questionnaires every 4 years. About 82% of the participants were women. At baseline, they reported consuming about one to four servings of dairy a day.

After adjustment for race, body mass index, calorie intake, family history, physical activity, and other factors associated with type 2 diabetes, the investigators found that increasing yogurt intake by one 4-ounce serving a day while decreasing cheese intake by one 1-ounce serving a day was associated with a 16% (95% confidence interval, 10%-22%) reduction in subsequent risk of type 2 disease. There was an 11% (95% CI, 7%-15%) reduction in risk when a cheese serving was subbed out for a daily 8-ounce serving of reduced-fat milk.

An extra 2 ounces of yogurt a day was associated with a 13% (95% CI, 6%-19%) lower risk of type 2 diabetes, compared with stable consumption, while an extra half ounce of cheese was associated with an 8% (95% CI, 2%-16%) increase in risk.

Overall, substitution of low-fat products (such as 0%-2% milk and low-fat cheese, yogurt, or sherbet) for high-fat products (such as whole milk, ice cream, and high-fat cheese) was associated with a 4% decrease in risk (hazard ratio, 0.96; 95% CI, 0.93-0.99).

However, substitution of reduced-fat milk for whole milk or low-fat cheese for high-fat cheese did not influence the risk, possibly because there is actually not much difference in fat content, Dr. Drouin-Chartier said.

The National Institutes of Health funded the study. Dr. Drouin-Chartier has served as a speaker and consultant for Dairy Farmers of Canada, one other author has advised the group, another has advised the U.S. Department of Agriculture, and the remaining authors had no disclosures.

SOURCE: Drouin-Chartier J et al. ADA 2019, Abstract 159-OR.

SAN FRANCISCO – Type 2 diabetes is much more aggressive in adolescents than in adults, and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.

M. Alexander Otto/Mdedge News

“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”

In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.

Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.

M. Alexander Otto/MDedge News

“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”

Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).

In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A_1c.

Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.

Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.

He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.

In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”

The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.

TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.

Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.

But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
 

Cardiovascular complications

The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.

Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
 

Decline renal function

In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.

So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
 

Pregnancy outcomes

Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.

There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.

Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.

In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.

Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.

In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A_1c level of more than 8%.
 

Retinopathy

Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).

None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
 

Neuropathy

The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.

“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.

There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.

Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A_1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).

The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.

[email protected]

This article was updated 7/22/19.

SAN FRANCISCO – Type 2 diabetes is much more aggressive in adolescents than in adults, and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.

M. Alexander Otto/Mdedge News

“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”

In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.

Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.

M. Alexander Otto/MDedge News

“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”

Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).

In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A_1c.

Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.

Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.

He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.

In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”

The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.

TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.

Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.

But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
 

Cardiovascular complications

The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.

Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
 

Decline renal function

In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.

So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
 

Pregnancy outcomes

Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.

There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.

Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.

In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.

Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.

In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A_1c level of more than 8%.
 

Retinopathy

Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).

None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
 

Neuropathy

The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.

“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.

There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.

Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A_1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).

The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.

[email protected]

This article was updated 7/22/19.

SAN FRANCISCO – Type 2 diabetes is much more aggressive in adolescents than in adults, and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.

M. Alexander Otto/Mdedge News

“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”

In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.

Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.

M. Alexander Otto/MDedge News

“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”

Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).

In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A_1c.

Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.

Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.

He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.

In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”

The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.

TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.

Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.

But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
 

Cardiovascular complications

The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.

Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
 

Decline renal function

In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.

So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
 

Pregnancy outcomes

Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.

There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.

Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.

In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.

Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.

In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A_1c level of more than 8%.
 

Retinopathy

Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).

None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
 

Neuropathy

The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.

“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.

There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.

Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A_1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).

The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.

[email protected]

This article was updated 7/22/19.

SAN FRANCISCO – Used appropriately, the benefits of benzodiazepines far outweigh the risks in elderly people, according to Carl Salzman, MD, a psychiatry professor at Harvard Medical School, Boston.

M. Alexander Otto/MDedge News

Appropriate use means very low doses – 0.5 mg or less every day or b.i.d. – of short-acting benzodiazepines, either lorazepam, oxazepam, or temazepam. There’s no worry of dose escalation or addiction in the elderly, and since the drugs are not metabolized by the cytochrome P450 system, the risk of drug interactions is very small, except for a compounding effect with alcohol and other sedative hypnotics, such as zolpidem (Ambien). The fall risk is lower than it is with antidepressants and antipsychotics (Psychiatr Serv. 2003 Jul;54[7]:1006-1); (Arch Intern Med. 2009 Nov 23;169[21]:1952-60).

In short, the drugs are “wonderful” for geriatric anxiety and anxiety-related insomnia, Dr. Salzman said at the American Psychiatric Association annual meeting.

Even so, it’s “very hard to get doctors and residents to prescribe them.” It’s like the benzodiazepine scare in the 1980s, about valium. “Newspapers were filled with stories about addicts. I’m having a little bit of déjà vu all over again,” he said.

This time around, the problem is a concern that benzodiazepines cause Alzheimer’s disease, plus collateral damage from the opioid crisis. People with addiction to opioids like benzodiazepines, because they boost the high, so they have significant street value, and drug seekers demand them in the clinic. Some clinicians would rather not deal with the drugs at all.

The Alzheimer’s worry stems largely from a widely reported review that found an association between Alzheimer’s disease and previous benzodiazepine use. The finding was based on public health insurance data from Quebec; no patients were seen (BMJ. 2014 Sep 9;349:g5205).

Among many “very large questions” about the study’s validity, people “may have been on benzos because they already had memory impairment and were anxious about it,” a common occurrence. In that case, “it’s not that benzos caused dementia; it was the other way around.” Also, there was no control for substance and alcohol use, Dr. Salzman said (J Clin Psychopharmacol. 2015 Feb;35[1]:1-3).

A more robust study followed patients 65 years and older for a mean of 7.3 years, comparing benzodiazepine users to nonusers. The team found a slightly higher risk of dementia in people with minimal exposure to benzodiazepines but not with the highest level of exposure, and concluded that the finding did “not support a causal association between benzodiazepine use and dementia” (BMJ. 2016 Feb 2;352:i90).

Meanwhile, a recent review of more than a million patients found either no or a minor increased risk of mortality, another concern with benzodiazepines in the elderly. “If a detrimental effect exists, it is likely to be much smaller than previously stated and to have uncertain clinical relevance. Residual confounding likely explains at least part of” it, the investigators concluded (BMJ. 2017 Jul 6;358:j294).

To be sure, short-term memory loss can occur with benzodiazepines, but patients did not seem to mind in a study Dr. Salzman conducted years ago in an upscale nursing home in Boston. A “dramatic” rebound was reported in short-term recall 2 weeks after volunteers tapered off benzodiazepines, mostly lorazepam, compared with those who stayed on them.

“I sat down to have lunch with the discontinuers, and I said to them, ‘Aren’t you glad that you are not taking these horrible drugs anymore, and your memory is so much better? They said, ‘No, what’s to remember? It was true that when we were taking those drugs, we might not have remembered what we watched on television the night before, but if you give a choice between feeling calm in the days, sleeping at night, and remembering what we watch on television, we’ll take the calm and the sleep every time,’ ” Dr. Salzman said.

He had no disclosures.

[email protected]

SAN FRANCISCO – Used appropriately, the benefits of benzodiazepines far outweigh the risks in elderly people, according to Carl Salzman, MD, a psychiatry professor at Harvard Medical School, Boston.

M. Alexander Otto/MDedge News

Appropriate use means very low doses – 0.5 mg or less every day or b.i.d. – of short-acting benzodiazepines, either lorazepam, oxazepam, or temazepam. There’s no worry of dose escalation or addiction in the elderly, and since the drugs are not metabolized by the cytochrome P450 system, the risk of drug interactions is very small, except for a compounding effect with alcohol and other sedative hypnotics, such as zolpidem (Ambien). The fall risk is lower than it is with antidepressants and antipsychotics (Psychiatr Serv. 2003 Jul;54[7]:1006-1); (Arch Intern Med. 2009 Nov 23;169[21]:1952-60).

In short, the drugs are “wonderful” for geriatric anxiety and anxiety-related insomnia, Dr. Salzman said at the American Psychiatric Association annual meeting.

Even so, it’s “very hard to get doctors and residents to prescribe them.” It’s like the benzodiazepine scare in the 1980s, about valium. “Newspapers were filled with stories about addicts. I’m having a little bit of déjà vu all over again,” he said.

This time around, the problem is a concern that benzodiazepines cause Alzheimer’s disease, plus collateral damage from the opioid crisis. People with addiction to opioids like benzodiazepines, because they boost the high, so they have significant street value, and drug seekers demand them in the clinic. Some clinicians would rather not deal with the drugs at all.

The Alzheimer’s worry stems largely from a widely reported review that found an association between Alzheimer’s disease and previous benzodiazepine use. The finding was based on public health insurance data from Quebec; no patients were seen (BMJ. 2014 Sep 9;349:g5205).

Among many “very large questions” about the study’s validity, people “may have been on benzos because they already had memory impairment and were anxious about it,” a common occurrence. In that case, “it’s not that benzos caused dementia; it was the other way around.” Also, there was no control for substance and alcohol use, Dr. Salzman said (J Clin Psychopharmacol. 2015 Feb;35[1]:1-3).

A more robust study followed patients 65 years and older for a mean of 7.3 years, comparing benzodiazepine users to nonusers. The team found a slightly higher risk of dementia in people with minimal exposure to benzodiazepines but not with the highest level of exposure, and concluded that the finding did “not support a causal association between benzodiazepine use and dementia” (BMJ. 2016 Feb 2;352:i90).

Meanwhile, a recent review of more than a million patients found either no or a minor increased risk of mortality, another concern with benzodiazepines in the elderly. “If a detrimental effect exists, it is likely to be much smaller than previously stated and to have uncertain clinical relevance. Residual confounding likely explains at least part of” it, the investigators concluded (BMJ. 2017 Jul 6;358:j294).

To be sure, short-term memory loss can occur with benzodiazepines, but patients did not seem to mind in a study Dr. Salzman conducted years ago in an upscale nursing home in Boston. A “dramatic” rebound was reported in short-term recall 2 weeks after volunteers tapered off benzodiazepines, mostly lorazepam, compared with those who stayed on them.

“I sat down to have lunch with the discontinuers, and I said to them, ‘Aren’t you glad that you are not taking these horrible drugs anymore, and your memory is so much better? They said, ‘No, what’s to remember? It was true that when we were taking those drugs, we might not have remembered what we watched on television the night before, but if you give a choice between feeling calm in the days, sleeping at night, and remembering what we watch on television, we’ll take the calm and the sleep every time,’ ” Dr. Salzman said.

He had no disclosures.

[email protected]

SAN FRANCISCO – Used appropriately, the benefits of benzodiazepines far outweigh the risks in elderly people, according to Carl Salzman, MD, a psychiatry professor at Harvard Medical School, Boston.

M. Alexander Otto/MDedge News

Appropriate use means very low doses – 0.5 mg or less every day or b.i.d. – of short-acting benzodiazepines, either lorazepam, oxazepam, or temazepam. There’s no worry of dose escalation or addiction in the elderly, and since the drugs are not metabolized by the cytochrome P450 system, the risk of drug interactions is very small, except for a compounding effect with alcohol and other sedative hypnotics, such as zolpidem (Ambien). The fall risk is lower than it is with antidepressants and antipsychotics (Psychiatr Serv. 2003 Jul;54[7]:1006-1); (Arch Intern Med. 2009 Nov 23;169[21]:1952-60).

In short, the drugs are “wonderful” for geriatric anxiety and anxiety-related insomnia, Dr. Salzman said at the American Psychiatric Association annual meeting.

Even so, it’s “very hard to get doctors and residents to prescribe them.” It’s like the benzodiazepine scare in the 1980s, about valium. “Newspapers were filled with stories about addicts. I’m having a little bit of déjà vu all over again,” he said.

This time around, the problem is a concern that benzodiazepines cause Alzheimer’s disease, plus collateral damage from the opioid crisis. People with addiction to opioids like benzodiazepines, because they boost the high, so they have significant street value, and drug seekers demand them in the clinic. Some clinicians would rather not deal with the drugs at all.

The Alzheimer’s worry stems largely from a widely reported review that found an association between Alzheimer’s disease and previous benzodiazepine use. The finding was based on public health insurance data from Quebec; no patients were seen (BMJ. 2014 Sep 9;349:g5205).

Among many “very large questions” about the study’s validity, people “may have been on benzos because they already had memory impairment and were anxious about it,” a common occurrence. In that case, “it’s not that benzos caused dementia; it was the other way around.” Also, there was no control for substance and alcohol use, Dr. Salzman said (J Clin Psychopharmacol. 2015 Feb;35[1]:1-3).

A more robust study followed patients 65 years and older for a mean of 7.3 years, comparing benzodiazepine users to nonusers. The team found a slightly higher risk of dementia in people with minimal exposure to benzodiazepines but not with the highest level of exposure, and concluded that the finding did “not support a causal association between benzodiazepine use and dementia” (BMJ. 2016 Feb 2;352:i90).

Meanwhile, a recent review of more than a million patients found either no or a minor increased risk of mortality, another concern with benzodiazepines in the elderly. “If a detrimental effect exists, it is likely to be much smaller than previously stated and to have uncertain clinical relevance. Residual confounding likely explains at least part of” it, the investigators concluded (BMJ. 2017 Jul 6;358:j294).

To be sure, short-term memory loss can occur with benzodiazepines, but patients did not seem to mind in a study Dr. Salzman conducted years ago in an upscale nursing home in Boston. A “dramatic” rebound was reported in short-term recall 2 weeks after volunteers tapered off benzodiazepines, mostly lorazepam, compared with those who stayed on them.

“I sat down to have lunch with the discontinuers, and I said to them, ‘Aren’t you glad that you are not taking these horrible drugs anymore, and your memory is so much better? They said, ‘No, what’s to remember? It was true that when we were taking those drugs, we might not have remembered what we watched on television the night before, but if you give a choice between feeling calm in the days, sleeping at night, and remembering what we watch on television, we’ll take the calm and the sleep every time,’ ” Dr. Salzman said.

He had no disclosures.

[email protected]

SAN FRANCISCO – Patients with diabetes might soon be able to wear a necklace that warns of impending hypoglycemia 15 minutes or more before continuous glucose monitors notice a problem, according to investigators from Indiana University-Purdue University, Indianapolis.

M. Alexander Otto/MDedge News

The device would detect changes in the volatile organic compounds (VOCs) that patients exhale as their plasma glucose level drops. In an insulin clamp study in 11 people with type 1 diabetes, the Indianapolis team found a marked shift in VOCs at a plasma glucose level of 90 mg/dL that persisted all the way down to a level of 50 mg/dL.

The team is now working on a sensor to detect that shift and alert patients. It’s the same trick that diabetes alert dogs do – minus the pup.

The device would be worn like a necklace, and “sense the air around your breath every 15 minutes or so,” said lead investigator Amanda P. Siegel, PhD, an analytical chemist and assistant research professor at the university.

Some continuous glucose monitors already warn of impending hypoglycemia, but the interstitial glucose levels on which they rely lag behind plasma glucose level by about 15 minutes or so. A VOC sniffer offers the hope of a real-time warning, Dr. Siegel said at the annual scientific sessions of the American Diabetes Association.

The team used gas chromatography–mass spectrometry to analyze 94 breath samples from the 11 participants, starting at a median fasting plasma glucose level of 150 mg/dL all the way down to 50 mg/dL, and back up to recovery. Samples collected at the 90-mg/dL and 80-mg/dL levels demonstrated VOC concentrations very similar to those at and below the hypoglycemia threshold of 70 mg/dL.

Even at 90 mg/dL, the VOC profile “looked like patients were already low. These volatile compounds change early” and stay on the breath as plasma glucose drops. “They are different from normal levels for the entire time, and separate out nicely,” Dr. Siegel said.

The team is not saying which volatile compounds are involved while the sensor is under development. They are looking for funding, and if all goes well, they hope to submit a device application to the Food and Drug Administration in 2020.

Other teams are also looking to VOCs to replace poor Fido, but he can alert to hyperglycemia and other problems as well, so his job is safe for now.

The work has been supported by the National Science Foundation. Dr. Siegel did not have any disclosures.

[email protected]

SOURCE: Siegel AP et al. ADA 2019, Abstract 968-P.

SAN FRANCISCO – Patients with diabetes might soon be able to wear a necklace that warns of impending hypoglycemia 15 minutes or more before continuous glucose monitors notice a problem, according to investigators from Indiana University-Purdue University, Indianapolis.

M. Alexander Otto/MDedge News

The device would detect changes in the volatile organic compounds (VOCs) that patients exhale as their plasma glucose level drops. In an insulin clamp study in 11 people with type 1 diabetes, the Indianapolis team found a marked shift in VOCs at a plasma glucose level of 90 mg/dL that persisted all the way down to a level of 50 mg/dL.

The team is now working on a sensor to detect that shift and alert patients. It’s the same trick that diabetes alert dogs do – minus the pup.

The device would be worn like a necklace, and “sense the air around your breath every 15 minutes or so,” said lead investigator Amanda P. Siegel, PhD, an analytical chemist and assistant research professor at the university.

Some continuous glucose monitors already warn of impending hypoglycemia, but the interstitial glucose levels on which they rely lag behind plasma glucose level by about 15 minutes or so. A VOC sniffer offers the hope of a real-time warning, Dr. Siegel said at the annual scientific sessions of the American Diabetes Association.

The team used gas chromatography–mass spectrometry to analyze 94 breath samples from the 11 participants, starting at a median fasting plasma glucose level of 150 mg/dL all the way down to 50 mg/dL, and back up to recovery. Samples collected at the 90-mg/dL and 80-mg/dL levels demonstrated VOC concentrations very similar to those at and below the hypoglycemia threshold of 70 mg/dL.

Even at 90 mg/dL, the VOC profile “looked like patients were already low. These volatile compounds change early” and stay on the breath as plasma glucose drops. “They are different from normal levels for the entire time, and separate out nicely,” Dr. Siegel said.

The team is not saying which volatile compounds are involved while the sensor is under development. They are looking for funding, and if all goes well, they hope to submit a device application to the Food and Drug Administration in 2020.

Other teams are also looking to VOCs to replace poor Fido, but he can alert to hyperglycemia and other problems as well, so his job is safe for now.

The work has been supported by the National Science Foundation. Dr. Siegel did not have any disclosures.

[email protected]

SOURCE: Siegel AP et al. ADA 2019, Abstract 968-P.

SAN FRANCISCO – Patients with diabetes might soon be able to wear a necklace that warns of impending hypoglycemia 15 minutes or more before continuous glucose monitors notice a problem, according to investigators from Indiana University-Purdue University, Indianapolis.

M. Alexander Otto/MDedge News

The device would detect changes in the volatile organic compounds (VOCs) that patients exhale as their plasma glucose level drops. In an insulin clamp study in 11 people with type 1 diabetes, the Indianapolis team found a marked shift in VOCs at a plasma glucose level of 90 mg/dL that persisted all the way down to a level of 50 mg/dL.

The team is now working on a sensor to detect that shift and alert patients. It’s the same trick that diabetes alert dogs do – minus the pup.

The device would be worn like a necklace, and “sense the air around your breath every 15 minutes or so,” said lead investigator Amanda P. Siegel, PhD, an analytical chemist and assistant research professor at the university.

Some continuous glucose monitors already warn of impending hypoglycemia, but the interstitial glucose levels on which they rely lag behind plasma glucose level by about 15 minutes or so. A VOC sniffer offers the hope of a real-time warning, Dr. Siegel said at the annual scientific sessions of the American Diabetes Association.

The team used gas chromatography–mass spectrometry to analyze 94 breath samples from the 11 participants, starting at a median fasting plasma glucose level of 150 mg/dL all the way down to 50 mg/dL, and back up to recovery. Samples collected at the 90-mg/dL and 80-mg/dL levels demonstrated VOC concentrations very similar to those at and below the hypoglycemia threshold of 70 mg/dL.

Even at 90 mg/dL, the VOC profile “looked like patients were already low. These volatile compounds change early” and stay on the breath as plasma glucose drops. “They are different from normal levels for the entire time, and separate out nicely,” Dr. Siegel said.

The team is not saying which volatile compounds are involved while the sensor is under development. They are looking for funding, and if all goes well, they hope to submit a device application to the Food and Drug Administration in 2020.

Other teams are also looking to VOCs to replace poor Fido, but he can alert to hyperglycemia and other problems as well, so his job is safe for now.

The work has been supported by the National Science Foundation. Dr. Siegel did not have any disclosures.

[email protected]

SOURCE: Siegel AP et al. ADA 2019, Abstract 968-P.

SAN FRANCISCO – The sulfonylurea glimepiride (Amaryl) did not increase the risk of cardiovascular events in patients with type 2 diabetes and cardiovascular risk in a head-to-head comparison with the dipeptidyl peptidase–4 (DPP-4) inhibitor linagliptin (Tradjenta), a drug with proven cardiovascular safety, according to findings from the CAROLINA study presented at the scientific sessions of the American Diabetes Association.

Linagliptin’s cardiovascular safety, compared with placebo, was demonstrated in the CARMELINA study (JAMA. 2019;321[1]:69-79), but CAROLINA pitted the DPP-4 inhibitor against an active comparator, glimepiride, which along with other sulfonylureas, carries a warning for increased risk of cardiovascular mortality. The latest findings about the comparator were not expected, but seem to set aside the lingering doubts about cardiovascular safety in at least the modern-day sulfonylureas.

“The stigma that sulfonylureas have had for more than 50 years” has been lifted. “We take a lot of pride in this study,” said principal investigator and endocrinologist Julio Rosenstock, MD, a clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.

In 1970, the University Group Diabetes Program trial reported 26 cardiovascular deaths in 204 patients who received with tolbutamide – a first-generation sulfonylurea no longer in common use – compared with 10 deaths in 205 patients who received placebo (Diabetes. 1970;19[Suppl]:789-830). The finding led to a warning of increased risk of cardiovascular mortality that still appears on sulfonylurea labels today.

The results were never confirmed by subsequent studies, and debate about the cardiovascular safety of sulfonylureas continued, with many physicians over the years calling for a large, rigorous trial to resolve the issue once and for all.

M. Alexander Otto/MDedge News

However, even with the new data, “the only reason I would [use a sulfonylurea] is cost. Cost is the bottom line in the clinic,” added Dr. Eckel, a professor of medicine at the University of Colorado, Aurora.

The trial findings pose no challenge to current guidelines for type 2 diabetes and the recommendation to opt first for a second-line medication with proven cardiovascular benefit, such as a sodium-glucose transporter 2 inhibitor or glucagonlike peptide–1 receptor agonist, in at-risk patients.

Boehringer Ingelheim, the maker of linagliptin, funded the study in collaboration with comarketer, Eli Lilly. Dr. Rosenstock and Dr. Marx disclosed numerous ties to Boehringer Ingelheim and Eli Lilly, and other companies not associated with the study. Dr. Eckel disclosed ties with companies not associated with the study.

[email protected]

SOURCE: Rosenstock J et al. ADA 2019.

SAN FRANCISCO – The sulfonylurea glimepiride (Amaryl) did not increase the risk of cardiovascular events in patients with type 2 diabetes and cardiovascular risk in a head-to-head comparison with the dipeptidyl peptidase–4 (DPP-4) inhibitor linagliptin (Tradjenta), a drug with proven cardiovascular safety, according to findings from the CAROLINA study presented at the scientific sessions of the American Diabetes Association.

Linagliptin’s cardiovascular safety, compared with placebo, was demonstrated in the CARMELINA study (JAMA. 2019;321[1]:69-79), but CAROLINA pitted the DPP-4 inhibitor against an active comparator, glimepiride, which along with other sulfonylureas, carries a warning for increased risk of cardiovascular mortality. The latest findings about the comparator were not expected, but seem to set aside the lingering doubts about cardiovascular safety in at least the modern-day sulfonylureas.

“The stigma that sulfonylureas have had for more than 50 years” has been lifted. “We take a lot of pride in this study,” said principal investigator and endocrinologist Julio Rosenstock, MD, a clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.

In 1970, the University Group Diabetes Program trial reported 26 cardiovascular deaths in 204 patients who received with tolbutamide – a first-generation sulfonylurea no longer in common use – compared with 10 deaths in 205 patients who received placebo (Diabetes. 1970;19[Suppl]:789-830). The finding led to a warning of increased risk of cardiovascular mortality that still appears on sulfonylurea labels today.

The results were never confirmed by subsequent studies, and debate about the cardiovascular safety of sulfonylureas continued, with many physicians over the years calling for a large, rigorous trial to resolve the issue once and for all.

M. Alexander Otto/MDedge News

However, even with the new data, “the only reason I would [use a sulfonylurea] is cost. Cost is the bottom line in the clinic,” added Dr. Eckel, a professor of medicine at the University of Colorado, Aurora.

The trial findings pose no challenge to current guidelines for type 2 diabetes and the recommendation to opt first for a second-line medication with proven cardiovascular benefit, such as a sodium-glucose transporter 2 inhibitor or glucagonlike peptide–1 receptor agonist, in at-risk patients.

Boehringer Ingelheim, the maker of linagliptin, funded the study in collaboration with comarketer, Eli Lilly. Dr. Rosenstock and Dr. Marx disclosed numerous ties to Boehringer Ingelheim and Eli Lilly, and other companies not associated with the study. Dr. Eckel disclosed ties with companies not associated with the study.

[email protected]

SOURCE: Rosenstock J et al. ADA 2019.

SAN FRANCISCO – The sulfonylurea glimepiride (Amaryl) did not increase the risk of cardiovascular events in patients with type 2 diabetes and cardiovascular risk in a head-to-head comparison with the dipeptidyl peptidase–4 (DPP-4) inhibitor linagliptin (Tradjenta), a drug with proven cardiovascular safety, according to findings from the CAROLINA study presented at the scientific sessions of the American Diabetes Association.

Linagliptin’s cardiovascular safety, compared with placebo, was demonstrated in the CARMELINA study (JAMA. 2019;321[1]:69-79), but CAROLINA pitted the DPP-4 inhibitor against an active comparator, glimepiride, which along with other sulfonylureas, carries a warning for increased risk of cardiovascular mortality. The latest findings about the comparator were not expected, but seem to set aside the lingering doubts about cardiovascular safety in at least the modern-day sulfonylureas.

“The stigma that sulfonylureas have had for more than 50 years” has been lifted. “We take a lot of pride in this study,” said principal investigator and endocrinologist Julio Rosenstock, MD, a clinical professor of medicine at the University of Texas Southwestern Medical Center, Dallas.

In 1970, the University Group Diabetes Program trial reported 26 cardiovascular deaths in 204 patients who received with tolbutamide – a first-generation sulfonylurea no longer in common use – compared with 10 deaths in 205 patients who received placebo (Diabetes. 1970;19[Suppl]:789-830). The finding led to a warning of increased risk of cardiovascular mortality that still appears on sulfonylurea labels today.

The results were never confirmed by subsequent studies, and debate about the cardiovascular safety of sulfonylureas continued, with many physicians over the years calling for a large, rigorous trial to resolve the issue once and for all.

M. Alexander Otto/MDedge News

However, even with the new data, “the only reason I would [use a sulfonylurea] is cost. Cost is the bottom line in the clinic,” added Dr. Eckel, a professor of medicine at the University of Colorado, Aurora.

The trial findings pose no challenge to current guidelines for type 2 diabetes and the recommendation to opt first for a second-line medication with proven cardiovascular benefit, such as a sodium-glucose transporter 2 inhibitor or glucagonlike peptide–1 receptor agonist, in at-risk patients.

Boehringer Ingelheim, the maker of linagliptin, funded the study in collaboration with comarketer, Eli Lilly. Dr. Rosenstock and Dr. Marx disclosed numerous ties to Boehringer Ingelheim and Eli Lilly, and other companies not associated with the study. Dr. Eckel disclosed ties with companies not associated with the study.

[email protected]

SOURCE: Rosenstock J et al. ADA 2019.

SAN FRANCISCO – Electroconvulsive therapy and ketamine both work well for refractory depression, but ketamine had the edge in a small, open label trial at the University of California, Los Angeles.

M. Alexander Otto/MDedge News

“Over the short term,” even a single ketamine infusion may “be as effective as ... ECT for reducing overall depression, apathy, anhedonia, and suicidal ideation,” but ECT may be more durable, said investigator Katherine Narr, PhD, an associate professor of neurology, psychiatry, and biobehavioral sciences at the school.

The study begins to address an issue that’s probably on the minds of many these days: ECT or ketamine for refractory depression? ELEKT-D (Clinicaltrials.gov NCT03113968), a large randomized, trial is underway to answer the question, but results aren’t expected for a couple of years.

In the meantime, although there was no randomization or blinding, Dr. Narr’s results are informative.

Twenty-six adults received one ketamine infusion, 0.5 mg/kg over 40 minutes, while 36 had four over about 2 weeks. Ketamine patients were allowed to stay on antidepressants. Forty-seven subjects, meanwhile, had 11 ECT treatments over 3 weeks, before which all psychiatric medications were stopped. The Hamilton Depression Rating Scale (HDRS) was used to assess outcomes.

Suicidal ideation probability dropped from 86% to 51% in the ECT group, but from 75% to 37% after one ketamine infusion, and to 11% after four (P less than .0001). A single “ketamine infusion showed similar probability of suicidal ideation reduction as a full course of ECT,” Dr. Narr said at the American Psychiatric Association annual meeting.

Improvements in overall HDRS scores were also greater after both single and serial ketamine (P less than .001).

However, HDRS scores – particularly for suicidal ideation – were beginning to creep up in the ketamine arm after just 5 weeks, but remained largely stable in the ECT group even at 3 months. In both groups, “therapeutic benefits for apathy and anhedonia last longer than for suicidal ideation,” Dr. Narr said.

At the moment, “you can’t predict who’s going to respond” better to one option or the other, “but I’m sure” biomarkers for that “are coming,” she said. Patients were 40 years old, on average, with depression first diagnosed in their early 20s. ECT subjects were equally split between the sexes, while there were more men than women in the ketamine arm, and current episodes were longer (average 6.6 years ketamine versus 3.7 years ECT). Baseline apathy scores were slightly higher in the ketamine group.

The work was funded by the National Institutes of Health. Dr. Narr didn’t have any disclosures.

[email protected]

SOURCE: Narr K et al., Presented at APA 2019

SAN FRANCISCO – Electroconvulsive therapy and ketamine both work well for refractory depression, but ketamine had the edge in a small, open label trial at the University of California, Los Angeles.

M. Alexander Otto/MDedge News

“Over the short term,” even a single ketamine infusion may “be as effective as ... ECT for reducing overall depression, apathy, anhedonia, and suicidal ideation,” but ECT may be more durable, said investigator Katherine Narr, PhD, an associate professor of neurology, psychiatry, and biobehavioral sciences at the school.

The study begins to address an issue that’s probably on the minds of many these days: ECT or ketamine for refractory depression? ELEKT-D (Clinicaltrials.gov NCT03113968), a large randomized, trial is underway to answer the question, but results aren’t expected for a couple of years.

In the meantime, although there was no randomization or blinding, Dr. Narr’s results are informative.

Twenty-six adults received one ketamine infusion, 0.5 mg/kg over 40 minutes, while 36 had four over about 2 weeks. Ketamine patients were allowed to stay on antidepressants. Forty-seven subjects, meanwhile, had 11 ECT treatments over 3 weeks, before which all psychiatric medications were stopped. The Hamilton Depression Rating Scale (HDRS) was used to assess outcomes.

Suicidal ideation probability dropped from 86% to 51% in the ECT group, but from 75% to 37% after one ketamine infusion, and to 11% after four (P less than .0001). A single “ketamine infusion showed similar probability of suicidal ideation reduction as a full course of ECT,” Dr. Narr said at the American Psychiatric Association annual meeting.

Improvements in overall HDRS scores were also greater after both single and serial ketamine (P less than .001).

However, HDRS scores – particularly for suicidal ideation – were beginning to creep up in the ketamine arm after just 5 weeks, but remained largely stable in the ECT group even at 3 months. In both groups, “therapeutic benefits for apathy and anhedonia last longer than for suicidal ideation,” Dr. Narr said.

At the moment, “you can’t predict who’s going to respond” better to one option or the other, “but I’m sure” biomarkers for that “are coming,” she said. Patients were 40 years old, on average, with depression first diagnosed in their early 20s. ECT subjects were equally split between the sexes, while there were more men than women in the ketamine arm, and current episodes were longer (average 6.6 years ketamine versus 3.7 years ECT). Baseline apathy scores were slightly higher in the ketamine group.

The work was funded by the National Institutes of Health. Dr. Narr didn’t have any disclosures.

[email protected]

SOURCE: Narr K et al., Presented at APA 2019

SAN FRANCISCO – Electroconvulsive therapy and ketamine both work well for refractory depression, but ketamine had the edge in a small, open label trial at the University of California, Los Angeles.

M. Alexander Otto/MDedge News

“Over the short term,” even a single ketamine infusion may “be as effective as ... ECT for reducing overall depression, apathy, anhedonia, and suicidal ideation,” but ECT may be more durable, said investigator Katherine Narr, PhD, an associate professor of neurology, psychiatry, and biobehavioral sciences at the school.

The study begins to address an issue that’s probably on the minds of many these days: ECT or ketamine for refractory depression? ELEKT-D (Clinicaltrials.gov NCT03113968), a large randomized, trial is underway to answer the question, but results aren’t expected for a couple of years.

In the meantime, although there was no randomization or blinding, Dr. Narr’s results are informative.

Twenty-six adults received one ketamine infusion, 0.5 mg/kg over 40 minutes, while 36 had four over about 2 weeks. Ketamine patients were allowed to stay on antidepressants. Forty-seven subjects, meanwhile, had 11 ECT treatments over 3 weeks, before which all psychiatric medications were stopped. The Hamilton Depression Rating Scale (HDRS) was used to assess outcomes.

Suicidal ideation probability dropped from 86% to 51% in the ECT group, but from 75% to 37% after one ketamine infusion, and to 11% after four (P less than .0001). A single “ketamine infusion showed similar probability of suicidal ideation reduction as a full course of ECT,” Dr. Narr said at the American Psychiatric Association annual meeting.

Improvements in overall HDRS scores were also greater after both single and serial ketamine (P less than .001).

However, HDRS scores – particularly for suicidal ideation – were beginning to creep up in the ketamine arm after just 5 weeks, but remained largely stable in the ECT group even at 3 months. In both groups, “therapeutic benefits for apathy and anhedonia last longer than for suicidal ideation,” Dr. Narr said.

At the moment, “you can’t predict who’s going to respond” better to one option or the other, “but I’m sure” biomarkers for that “are coming,” she said. Patients were 40 years old, on average, with depression first diagnosed in their early 20s. ECT subjects were equally split between the sexes, while there were more men than women in the ketamine arm, and current episodes were longer (average 6.6 years ketamine versus 3.7 years ECT). Baseline apathy scores were slightly higher in the ketamine group.

The work was funded by the National Institutes of Health. Dr. Narr didn’t have any disclosures.

[email protected]

SOURCE: Narr K et al., Presented at APA 2019

Janssen’s daratumumab (Darzalex) has picked up a sixth adult multiple myeloma indication, this time in combination with lenalidomide (Revlimid) and dexamethasone in newly diagnosed patients ineligible for autologous stem cell transplants.

The phase 3 MAIA trial found that 97 of 368 patients (26.4%) treated with the combination – dubbed DRd – progressed or died at a median follow-up of 28 months, versus 143 of 269 (38.8%) treated with lenalidomide and dexamethasone alone (Rd). An estimated 55.6% of patients on lenalidomide and dexamethasone, versus 70.6% with the daratumumab add-on, were alive without progression at 30 months (N Engl J Med. 2019 May 30;380[22]:2104-15).


Previously approved indications for daratumumab include relapsed or refractory disease after at least one other therapy; and combination treatment with bortezomib, melphalan, and prednisone, also in newly diagnosed patients who are ineligible for transplant.

The most common grade 3 and 4 adverse events reported in the MAIA trial were neutropenia (50.0% for the DRd group versus 35.3% for the Rd group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%).

[email protected]

Janssen’s daratumumab (Darzalex) has picked up a sixth adult multiple myeloma indication, this time in combination with lenalidomide (Revlimid) and dexamethasone in newly diagnosed patients ineligible for autologous stem cell transplants.

The phase 3 MAIA trial found that 97 of 368 patients (26.4%) treated with the combination – dubbed DRd – progressed or died at a median follow-up of 28 months, versus 143 of 269 (38.8%) treated with lenalidomide and dexamethasone alone (Rd). An estimated 55.6% of patients on lenalidomide and dexamethasone, versus 70.6% with the daratumumab add-on, were alive without progression at 30 months (N Engl J Med. 2019 May 30;380[22]:2104-15).


Previously approved indications for daratumumab include relapsed or refractory disease after at least one other therapy; and combination treatment with bortezomib, melphalan, and prednisone, also in newly diagnosed patients who are ineligible for transplant.

The most common grade 3 and 4 adverse events reported in the MAIA trial were neutropenia (50.0% for the DRd group versus 35.3% for the Rd group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%).

[email protected]

Janssen’s daratumumab (Darzalex) has picked up a sixth adult multiple myeloma indication, this time in combination with lenalidomide (Revlimid) and dexamethasone in newly diagnosed patients ineligible for autologous stem cell transplants.

The phase 3 MAIA trial found that 97 of 368 patients (26.4%) treated with the combination – dubbed DRd – progressed or died at a median follow-up of 28 months, versus 143 of 269 (38.8%) treated with lenalidomide and dexamethasone alone (Rd). An estimated 55.6% of patients on lenalidomide and dexamethasone, versus 70.6% with the daratumumab add-on, were alive without progression at 30 months (N Engl J Med. 2019 May 30;380[22]:2104-15).


Previously approved indications for daratumumab include relapsed or refractory disease after at least one other therapy; and combination treatment with bortezomib, melphalan, and prednisone, also in newly diagnosed patients who are ineligible for transplant.

The most common grade 3 and 4 adverse events reported in the MAIA trial were neutropenia (50.0% for the DRd group versus 35.3% for the Rd group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%).

[email protected]