Diabetes Hub

VIENNA – The beneficial effects of aflibercept on diabetic eye disease are independent of how well blood glucose is being controlled at the start of treatment, according to a post hoc analysis of two randomized, phase III studies.

Intravitreal injection of 2 mg of aflibercept every month or every other month had similar effects on the primary endpoint of best-corrected visual acuity (BCVA) in more than 800 subjects with diabetic macular edema (DME) with central involvement. BCVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.

The mean change in BCVA from baseline to 1-year follow-up was increased by around 11 letters with aflibercept treatment regardless of which quartile of hemoglobin A_1c patients fit into at study entry. In contrast, patients treated with laser therapy appeared to have lessening benefit from treatment as baseline HbA_1c increased, with an improvement of 4.1 letters in the first to –0.3 letters in the fourth HbA1c quartiles.

Aflibercept-treated patients also experienced a significant decrease in central retinal thickness (CRT) compared with laser therapy. The mean change in CRT from baseline to 1 year was –201 micrometers in aflibercept-treated patients with a baseline HbA_1c of between 4.5% and less than 6.5% (quartile 1), and –195, –196, and –188 micrometers in patients with HbA1c levels of 6.7% to less than 7.4% (quartile 2), 7.4% to less than 8.6% (quartile 3), and 8.6% to 14.7% (quartile 4). Corresponding values for laser therapy were –102, –83, –69, and –43 micometers.

“The findings show that improvements achieved with intravitreal aflibercept over laser in anatomical and functional outcomes – best-corrected visual acuity and central retinal thickness – were robust and similar in patients even with variable systemic disease control at baseline,” said Dr. Oliver Zeitz of Bayer HealthCare, which sponsored the study and markets aflibercept (Eylea) in conjunction with Regeneron Pharmaceuticals.

“Furthermore, we could see in these trials, in the overall population, we could observe improvement in diabetic retinopathy severity scale, which may indicate that aflibercept is not only efficacious on treating DME but also has a potentially beneficial effect on the underlying diabetic retinopathy,” Dr. Zeitz added when presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

VIVID-DME and VISTA-DME are two similarly designed, ongoing studies that are evaluating the efficacy and safety of intravitreal aflibercept injection for the treatment of DME versus laser photocoagulation. A total of 872 patients were randomized in both trials to receive aflibercept 2 mg every 4 or 8 weeks plus a sham laser treatment, or to macular laser photocoagulation plus sham intravitreal therapy.

Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor especially formulated for injection into the eye. The rationale for using the drug is that it helps stop the growth of new blood vessels that will obscure visions if left unchecked. It also decreases vascular permeability in the eye by blocking VEGF-A and placental growth factor.

Intravitreal aflibercept is approved in the United States and the European Union and several other countries for the management of wet age-related macular degeneration and for macular edema after central retinal vein occlusion. The drug has also just received FDA approval for the treatment of DME, according to a Regeneron statement.

Safety is, of course, an important consideration, Dr. Zeitz said, adding that there was a similar overall incidence of ocular and nonocular adverse events. There was also no difference in ocular serious adverse events, including arterial thromboembolic events as defined by the Anti-Platelet Trialists’ Collaboration. There were no cases of endophthalmitis reported.

Dr. Zeitz and his coauthors are employees of Bayer HealthCare, which sponsored the VISTA- and VIVID-DME studies.

VIENNA – The beneficial effects of aflibercept on diabetic eye disease are independent of how well blood glucose is being controlled at the start of treatment, according to a post hoc analysis of two randomized, phase III studies.

Intravitreal injection of 2 mg of aflibercept every month or every other month had similar effects on the primary endpoint of best-corrected visual acuity (BCVA) in more than 800 subjects with diabetic macular edema (DME) with central involvement. BCVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.

The mean change in BCVA from baseline to 1-year follow-up was increased by around 11 letters with aflibercept treatment regardless of which quartile of hemoglobin A_1c patients fit into at study entry. In contrast, patients treated with laser therapy appeared to have lessening benefit from treatment as baseline HbA_1c increased, with an improvement of 4.1 letters in the first to –0.3 letters in the fourth HbA1c quartiles.

Aflibercept-treated patients also experienced a significant decrease in central retinal thickness (CRT) compared with laser therapy. The mean change in CRT from baseline to 1 year was –201 micrometers in aflibercept-treated patients with a baseline HbA_1c of between 4.5% and less than 6.5% (quartile 1), and –195, –196, and –188 micrometers in patients with HbA1c levels of 6.7% to less than 7.4% (quartile 2), 7.4% to less than 8.6% (quartile 3), and 8.6% to 14.7% (quartile 4). Corresponding values for laser therapy were –102, –83, –69, and –43 micometers.

“The findings show that improvements achieved with intravitreal aflibercept over laser in anatomical and functional outcomes – best-corrected visual acuity and central retinal thickness – were robust and similar in patients even with variable systemic disease control at baseline,” said Dr. Oliver Zeitz of Bayer HealthCare, which sponsored the study and markets aflibercept (Eylea) in conjunction with Regeneron Pharmaceuticals.

“Furthermore, we could see in these trials, in the overall population, we could observe improvement in diabetic retinopathy severity scale, which may indicate that aflibercept is not only efficacious on treating DME but also has a potentially beneficial effect on the underlying diabetic retinopathy,” Dr. Zeitz added when presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

VIVID-DME and VISTA-DME are two similarly designed, ongoing studies that are evaluating the efficacy and safety of intravitreal aflibercept injection for the treatment of DME versus laser photocoagulation. A total of 872 patients were randomized in both trials to receive aflibercept 2 mg every 4 or 8 weeks plus a sham laser treatment, or to macular laser photocoagulation plus sham intravitreal therapy.

Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor especially formulated for injection into the eye. The rationale for using the drug is that it helps stop the growth of new blood vessels that will obscure visions if left unchecked. It also decreases vascular permeability in the eye by blocking VEGF-A and placental growth factor.

Intravitreal aflibercept is approved in the United States and the European Union and several other countries for the management of wet age-related macular degeneration and for macular edema after central retinal vein occlusion. The drug has also just received FDA approval for the treatment of DME, according to a Regeneron statement.

Safety is, of course, an important consideration, Dr. Zeitz said, adding that there was a similar overall incidence of ocular and nonocular adverse events. There was also no difference in ocular serious adverse events, including arterial thromboembolic events as defined by the Anti-Platelet Trialists’ Collaboration. There were no cases of endophthalmitis reported.

Dr. Zeitz and his coauthors are employees of Bayer HealthCare, which sponsored the VISTA- and VIVID-DME studies.

VIENNA – The beneficial effects of aflibercept on diabetic eye disease are independent of how well blood glucose is being controlled at the start of treatment, according to a post hoc analysis of two randomized, phase III studies.

Intravitreal injection of 2 mg of aflibercept every month or every other month had similar effects on the primary endpoint of best-corrected visual acuity (BCVA) in more than 800 subjects with diabetic macular edema (DME) with central involvement. BCVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.

The mean change in BCVA from baseline to 1-year follow-up was increased by around 11 letters with aflibercept treatment regardless of which quartile of hemoglobin A_1c patients fit into at study entry. In contrast, patients treated with laser therapy appeared to have lessening benefit from treatment as baseline HbA_1c increased, with an improvement of 4.1 letters in the first to –0.3 letters in the fourth HbA1c quartiles.

Aflibercept-treated patients also experienced a significant decrease in central retinal thickness (CRT) compared with laser therapy. The mean change in CRT from baseline to 1 year was –201 micrometers in aflibercept-treated patients with a baseline HbA_1c of between 4.5% and less than 6.5% (quartile 1), and –195, –196, and –188 micrometers in patients with HbA1c levels of 6.7% to less than 7.4% (quartile 2), 7.4% to less than 8.6% (quartile 3), and 8.6% to 14.7% (quartile 4). Corresponding values for laser therapy were –102, –83, –69, and –43 micometers.

“The findings show that improvements achieved with intravitreal aflibercept over laser in anatomical and functional outcomes – best-corrected visual acuity and central retinal thickness – were robust and similar in patients even with variable systemic disease control at baseline,” said Dr. Oliver Zeitz of Bayer HealthCare, which sponsored the study and markets aflibercept (Eylea) in conjunction with Regeneron Pharmaceuticals.

“Furthermore, we could see in these trials, in the overall population, we could observe improvement in diabetic retinopathy severity scale, which may indicate that aflibercept is not only efficacious on treating DME but also has a potentially beneficial effect on the underlying diabetic retinopathy,” Dr. Zeitz added when presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

VIVID-DME and VISTA-DME are two similarly designed, ongoing studies that are evaluating the efficacy and safety of intravitreal aflibercept injection for the treatment of DME versus laser photocoagulation. A total of 872 patients were randomized in both trials to receive aflibercept 2 mg every 4 or 8 weeks plus a sham laser treatment, or to macular laser photocoagulation plus sham intravitreal therapy.

Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor especially formulated for injection into the eye. The rationale for using the drug is that it helps stop the growth of new blood vessels that will obscure visions if left unchecked. It also decreases vascular permeability in the eye by blocking VEGF-A and placental growth factor.

Intravitreal aflibercept is approved in the United States and the European Union and several other countries for the management of wet age-related macular degeneration and for macular edema after central retinal vein occlusion. The drug has also just received FDA approval for the treatment of DME, according to a Regeneron statement.

Safety is, of course, an important consideration, Dr. Zeitz said, adding that there was a similar overall incidence of ocular and nonocular adverse events. There was also no difference in ocular serious adverse events, including arterial thromboembolic events as defined by the Anti-Platelet Trialists’ Collaboration. There were no cases of endophthalmitis reported.

Dr. Zeitz and his coauthors are employees of Bayer HealthCare, which sponsored the VISTA- and VIVID-DME studies.

BARCELONA – In what is being called “the healthy immigrant effect,” Canadian investigators have found that adult diabetic immigrants from low-income countries with high cardiovascular mortality rates are relatively protected against cardiovascular events, compared with matched long-time or lifetime Canadian residents. This healthy immigrant effect appears to last for at least a decade following the immigrants’ arrival in their new land, and perhaps longer, Dr. Karen Okrainec reported at the annual congress of the European Society of Cardiology. Ontario is fertile territory in which to study the health of immigrants. Fully 43% of Ontario residents are foreign born, the highest proportion in all of Canada’s provinces, noted Dr. Okrainec of the University of Toronto.

She presented a population-based cohort study involving 87,707 adult diabetic subjects who immigrated to Ontario during 1965-2005 and an equal number of long-term or lifetime diabetic Ontario residents matched for age, sex, and neighborhood. Most of the immigrants came from South Asia and East Asia, although there were also significant numbers from the Caribbean, Sub-Saharan Africa, North Africa, and the Middle East, and Eastern and Western Europe. The immigrants had been in Canada for a mean of 11.6 years at the time of the analysis.

The primary outcome in the study was the composite endpoint of all-cause mortality or one or more hospitalizations or emergency department visits for acute MI, heart failure, unstable angina, stroke, or TIA between April 2005 and February 2012. There were 13,685 of these events among the immigrants, for an event rate of 2.4 cases/100 person-years.

This was fully 32% lower than the unadjusted event rate among the control group.

After researchers adjusted for years since diagnosis of diabetes, education level, income, the presence of hypertension, and other comorbid conditions, language barriers, marital status, and other potential confounders, they found that the risk of the composite endpoint remained 24% lower in immigrants than controls. Thus, it is clear there is not an accelerated risk of cardiovascular events among diabetic immigrants, despite their change in lifestyle in moving to a highly developed country where they may encounter cultural or language barriers to health care access, according to Dr. Okrainec.

Not all immigrants benefited from the healthy immigrant effect, however. Refugees did not. Neither did those who were single, nor did immigrants from Eastern and Central Europe or Latin America. Also, the healthy immigrant effect – the diabetic immigrants’ health advantage over longer-term Ontario residents – appeared to grow stronger with time; in other words, the healthy immigrant effect was weaker in those who arrived in Ontario less than 10 years earlier.

Dr. Okrainec’s study was funded by the Ontario Ministry of Health and Long-Term Care. She reported having no financial conflicts.

[email protected]

BARCELONA – In what is being called “the healthy immigrant effect,” Canadian investigators have found that adult diabetic immigrants from low-income countries with high cardiovascular mortality rates are relatively protected against cardiovascular events, compared with matched long-time or lifetime Canadian residents. This healthy immigrant effect appears to last for at least a decade following the immigrants’ arrival in their new land, and perhaps longer, Dr. Karen Okrainec reported at the annual congress of the European Society of Cardiology. Ontario is fertile territory in which to study the health of immigrants. Fully 43% of Ontario residents are foreign born, the highest proportion in all of Canada’s provinces, noted Dr. Okrainec of the University of Toronto.

She presented a population-based cohort study involving 87,707 adult diabetic subjects who immigrated to Ontario during 1965-2005 and an equal number of long-term or lifetime diabetic Ontario residents matched for age, sex, and neighborhood. Most of the immigrants came from South Asia and East Asia, although there were also significant numbers from the Caribbean, Sub-Saharan Africa, North Africa, and the Middle East, and Eastern and Western Europe. The immigrants had been in Canada for a mean of 11.6 years at the time of the analysis.

The primary outcome in the study was the composite endpoint of all-cause mortality or one or more hospitalizations or emergency department visits for acute MI, heart failure, unstable angina, stroke, or TIA between April 2005 and February 2012. There were 13,685 of these events among the immigrants, for an event rate of 2.4 cases/100 person-years.

This was fully 32% lower than the unadjusted event rate among the control group.

After researchers adjusted for years since diagnosis of diabetes, education level, income, the presence of hypertension, and other comorbid conditions, language barriers, marital status, and other potential confounders, they found that the risk of the composite endpoint remained 24% lower in immigrants than controls. Thus, it is clear there is not an accelerated risk of cardiovascular events among diabetic immigrants, despite their change in lifestyle in moving to a highly developed country where they may encounter cultural or language barriers to health care access, according to Dr. Okrainec.

Not all immigrants benefited from the healthy immigrant effect, however. Refugees did not. Neither did those who were single, nor did immigrants from Eastern and Central Europe or Latin America. Also, the healthy immigrant effect – the diabetic immigrants’ health advantage over longer-term Ontario residents – appeared to grow stronger with time; in other words, the healthy immigrant effect was weaker in those who arrived in Ontario less than 10 years earlier.

Dr. Okrainec’s study was funded by the Ontario Ministry of Health and Long-Term Care. She reported having no financial conflicts.

[email protected]

BARCELONA – In what is being called “the healthy immigrant effect,” Canadian investigators have found that adult diabetic immigrants from low-income countries with high cardiovascular mortality rates are relatively protected against cardiovascular events, compared with matched long-time or lifetime Canadian residents. This healthy immigrant effect appears to last for at least a decade following the immigrants’ arrival in their new land, and perhaps longer, Dr. Karen Okrainec reported at the annual congress of the European Society of Cardiology. Ontario is fertile territory in which to study the health of immigrants. Fully 43% of Ontario residents are foreign born, the highest proportion in all of Canada’s provinces, noted Dr. Okrainec of the University of Toronto.

She presented a population-based cohort study involving 87,707 adult diabetic subjects who immigrated to Ontario during 1965-2005 and an equal number of long-term or lifetime diabetic Ontario residents matched for age, sex, and neighborhood. Most of the immigrants came from South Asia and East Asia, although there were also significant numbers from the Caribbean, Sub-Saharan Africa, North Africa, and the Middle East, and Eastern and Western Europe. The immigrants had been in Canada for a mean of 11.6 years at the time of the analysis.

The primary outcome in the study was the composite endpoint of all-cause mortality or one or more hospitalizations or emergency department visits for acute MI, heart failure, unstable angina, stroke, or TIA between April 2005 and February 2012. There were 13,685 of these events among the immigrants, for an event rate of 2.4 cases/100 person-years.

This was fully 32% lower than the unadjusted event rate among the control group.

After researchers adjusted for years since diagnosis of diabetes, education level, income, the presence of hypertension, and other comorbid conditions, language barriers, marital status, and other potential confounders, they found that the risk of the composite endpoint remained 24% lower in immigrants than controls. Thus, it is clear there is not an accelerated risk of cardiovascular events among diabetic immigrants, despite their change in lifestyle in moving to a highly developed country where they may encounter cultural or language barriers to health care access, according to Dr. Okrainec.

Not all immigrants benefited from the healthy immigrant effect, however. Refugees did not. Neither did those who were single, nor did immigrants from Eastern and Central Europe or Latin America. Also, the healthy immigrant effect – the diabetic immigrants’ health advantage over longer-term Ontario residents – appeared to grow stronger with time; in other words, the healthy immigrant effect was weaker in those who arrived in Ontario less than 10 years earlier.

Dr. Okrainec’s study was funded by the Ontario Ministry of Health and Long-Term Care. She reported having no financial conflicts.

[email protected]

VIENNA – A “pragmatic and simple” approach to gradually lower the hemoglobin A1c level in patients with type 2 diabetes to 6.5% and then maintain it for an average of 5 years caused no suggestion of harm and led to an important halving of end-stage renal disease during 10-year follow-up in a controlled study with more than 8,000 patients, Dr. Sophia Zoungas said in an interview at the annual meeting of the European Association for the Study of Diabetes.

Intensive glucose control did not increase mortality or the rate of major macrovascular events in 10-year results from the ADVANCE ON (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Post Trial Observational Study) trial. The results also showed for the first time that intensive glucose control produced a significant and large reduction in end-stage kidney disease, said Dr. Zoungas, an endocrinologist with the George Institute of the University of Sydney.

ADVANCE ON received partial funding from Servier. Dr. Zoungas has received honoraria from Servier as well as from Merck Sharp & Dohme, Bristol-Myers Squibb/AstraZeneca, Sanofi-Aventis, Novo Nordisk, and Amgen.

[email protected]

On Twitter @mitchelzoler

VIENNA – A “pragmatic and simple” approach to gradually lower the hemoglobin A1c level in patients with type 2 diabetes to 6.5% and then maintain it for an average of 5 years caused no suggestion of harm and led to an important halving of end-stage renal disease during 10-year follow-up in a controlled study with more than 8,000 patients, Dr. Sophia Zoungas said in an interview at the annual meeting of the European Association for the Study of Diabetes.

Intensive glucose control did not increase mortality or the rate of major macrovascular events in 10-year results from the ADVANCE ON (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Post Trial Observational Study) trial. The results also showed for the first time that intensive glucose control produced a significant and large reduction in end-stage kidney disease, said Dr. Zoungas, an endocrinologist with the George Institute of the University of Sydney.

ADVANCE ON received partial funding from Servier. Dr. Zoungas has received honoraria from Servier as well as from Merck Sharp & Dohme, Bristol-Myers Squibb/AstraZeneca, Sanofi-Aventis, Novo Nordisk, and Amgen.

[email protected]

On Twitter @mitchelzoler

VIENNA – A “pragmatic and simple” approach to gradually lower the hemoglobin A1c level in patients with type 2 diabetes to 6.5% and then maintain it for an average of 5 years caused no suggestion of harm and led to an important halving of end-stage renal disease during 10-year follow-up in a controlled study with more than 8,000 patients, Dr. Sophia Zoungas said in an interview at the annual meeting of the European Association for the Study of Diabetes.

Intensive glucose control did not increase mortality or the rate of major macrovascular events in 10-year results from the ADVANCE ON (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Post Trial Observational Study) trial. The results also showed for the first time that intensive glucose control produced a significant and large reduction in end-stage kidney disease, said Dr. Zoungas, an endocrinologist with the George Institute of the University of Sydney.

ADVANCE ON received partial funding from Servier. Dr. Zoungas has received honoraria from Servier as well as from Merck Sharp & Dohme, Bristol-Myers Squibb/AstraZeneca, Sanofi-Aventis, Novo Nordisk, and Amgen.

[email protected]

On Twitter @mitchelzoler

The occurrence of diabetes has leveled off among U.S. adults in general, but has continued to rise among non-Hispanic blacks, Hispanics, and adults who did not study past high school, researchers from the Centers for Disease Control and Prevention reported Sept. 23 in JAMA.

In 2012, the estimated diabetes incidence was 7.1 cases per 1,000 adults (95% confidence interval, 6.1-8.2), and the prevalence was 8.3% (95% CI, 7.9%-8.7%), with no significant changes in either rate since 2008, said Linda Geiss and her associates at the CDC. The plateau could reflect stabilizations in U.S. obesity rates since 2003, and “appears to be concurrent with declines in overall caloric intake, food purchases, and energy intake,” the researchers said.

Wavebreakmedia Ltd

The study included National Health Interview Survey data collected between 1980 and 2012 from 664,969 U.S. adults aged 20-79 years old. Rates of type 1 and 2 diabetes rose by about 4.5% per year between 1990 and 2008, the researchers said. During that period, the estimated incidence of diabetes more than doubled from 3.1 to 8.8 cases per 1,000 persons, while prevalence climbed from 3.5% to 7.9%.

Changes in diagnostic practices could have fueled the increase, but were unlikely to fully explain the “strong and steady 15- to 20-year increase in diabetes prevalence and incidence,” Ms. Geiss and her associates added (JAMA 2014 Sept. 23;312:1218-26).

Despite the recent overall plateau, diabetes incidence continued to climb among Hispanics and non-Hispanic blacks between 2008 and 2012, while prevalence rose among adult Americans who had a high school education or less, said the investigators. “This threatens to exacerbate racial/ethnic and socioeconomic disparities in diabetes prevalence and incidence,” the researchers wrote. “Furthermore, in light of the well-known excess risk of amputation, blindness, end-stage renal disease, disability, mortality, and health care costs associated with diabetes, the doubling of diabetes incidence and prevalence ensures that diabetes will remain a major public health problem that demands effective prevention and management programs.”

The Centers for Disease Control National Center for Health Statistics collected the data. The authors reported having no relevant financial conflicts.

The occurrence of diabetes has leveled off among U.S. adults in general, but has continued to rise among non-Hispanic blacks, Hispanics, and adults who did not study past high school, researchers from the Centers for Disease Control and Prevention reported Sept. 23 in JAMA.

In 2012, the estimated diabetes incidence was 7.1 cases per 1,000 adults (95% confidence interval, 6.1-8.2), and the prevalence was 8.3% (95% CI, 7.9%-8.7%), with no significant changes in either rate since 2008, said Linda Geiss and her associates at the CDC. The plateau could reflect stabilizations in U.S. obesity rates since 2003, and “appears to be concurrent with declines in overall caloric intake, food purchases, and energy intake,” the researchers said.

Wavebreakmedia Ltd

The study included National Health Interview Survey data collected between 1980 and 2012 from 664,969 U.S. adults aged 20-79 years old. Rates of type 1 and 2 diabetes rose by about 4.5% per year between 1990 and 2008, the researchers said. During that period, the estimated incidence of diabetes more than doubled from 3.1 to 8.8 cases per 1,000 persons, while prevalence climbed from 3.5% to 7.9%.

Changes in diagnostic practices could have fueled the increase, but were unlikely to fully explain the “strong and steady 15- to 20-year increase in diabetes prevalence and incidence,” Ms. Geiss and her associates added (JAMA 2014 Sept. 23;312:1218-26).

Despite the recent overall plateau, diabetes incidence continued to climb among Hispanics and non-Hispanic blacks between 2008 and 2012, while prevalence rose among adult Americans who had a high school education or less, said the investigators. “This threatens to exacerbate racial/ethnic and socioeconomic disparities in diabetes prevalence and incidence,” the researchers wrote. “Furthermore, in light of the well-known excess risk of amputation, blindness, end-stage renal disease, disability, mortality, and health care costs associated with diabetes, the doubling of diabetes incidence and prevalence ensures that diabetes will remain a major public health problem that demands effective prevention and management programs.”

The Centers for Disease Control National Center for Health Statistics collected the data. The authors reported having no relevant financial conflicts.

The occurrence of diabetes has leveled off among U.S. adults in general, but has continued to rise among non-Hispanic blacks, Hispanics, and adults who did not study past high school, researchers from the Centers for Disease Control and Prevention reported Sept. 23 in JAMA.

In 2012, the estimated diabetes incidence was 7.1 cases per 1,000 adults (95% confidence interval, 6.1-8.2), and the prevalence was 8.3% (95% CI, 7.9%-8.7%), with no significant changes in either rate since 2008, said Linda Geiss and her associates at the CDC. The plateau could reflect stabilizations in U.S. obesity rates since 2003, and “appears to be concurrent with declines in overall caloric intake, food purchases, and energy intake,” the researchers said.

Wavebreakmedia Ltd

The study included National Health Interview Survey data collected between 1980 and 2012 from 664,969 U.S. adults aged 20-79 years old. Rates of type 1 and 2 diabetes rose by about 4.5% per year between 1990 and 2008, the researchers said. During that period, the estimated incidence of diabetes more than doubled from 3.1 to 8.8 cases per 1,000 persons, while prevalence climbed from 3.5% to 7.9%.

Changes in diagnostic practices could have fueled the increase, but were unlikely to fully explain the “strong and steady 15- to 20-year increase in diabetes prevalence and incidence,” Ms. Geiss and her associates added (JAMA 2014 Sept. 23;312:1218-26).

Despite the recent overall plateau, diabetes incidence continued to climb among Hispanics and non-Hispanic blacks between 2008 and 2012, while prevalence rose among adult Americans who had a high school education or less, said the investigators. “This threatens to exacerbate racial/ethnic and socioeconomic disparities in diabetes prevalence and incidence,” the researchers wrote. “Furthermore, in light of the well-known excess risk of amputation, blindness, end-stage renal disease, disability, mortality, and health care costs associated with diabetes, the doubling of diabetes incidence and prevalence ensures that diabetes will remain a major public health problem that demands effective prevention and management programs.”

The Centers for Disease Control National Center for Health Statistics collected the data. The authors reported having no relevant financial conflicts.

VIENNA – There is no increased risk for myocardial infarction or other vascular events from prolonged use of insulin in people with pre- or type 2 diabetes who are already at high risk for cardiovascular disease, according to additional follow-up data from the ORIGIN study.

The ORIGINALE (Origin and Legacy Effects) study provides an additional 2.5 years of observational follow-up of more than 8,000 of the 12,000-plus individuals who participated in the ORIGIN (Outcome Reduction with an Initial Glargine Intervention) study.

© iStock/ThinkStockPhotos

The results of the ORIGIN trial were that 6.2 years of treatment with insulin glargine (Sanofi’s Lantus) had a neutral effect on cardiovascular events and other serious health outcomes such as cancer, and possibly slowed diabetes progression (N. Engl. J. Med. 2012;367:319-28). In addition, omega-3 fatty acid supplementation was found to offer no benefit over placebo.

The results of the ORIGINALE study continue to support these findings, Dr. Hertzel C. Gerstein reported at the annual meeting of the European Society for the Study of Diabetes.

The key conclusion of ORIGIN and ORIGINALE with regard to insulin use is that “targeting a normal fasting plasma glucose with basal insulin glargine for more than 6 years improves metabolic status and has a neutral effect on serious health outcomes,” Dr. Gerstein of McMaster University, Hamilton, Ont., observed.

Two coprimary composite cardiovascular outcomes were assessed, neither of which showed any advantage or disadvantage of using insulin glargine versus standard care.

The hazard ratio for the first coprimary outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in ORIGINALE was 1.01, and the HR for the second coprimary endpoint of any cardiovascular event, a revascularization procedure, or hospitalization for heart failure was 1.03.

There was also a “neutral effect” on the individual components of these composite endpoints, with HRs of 1.02, 1.05, 1.00, 0.90, and 1.04 for myocardial infarction, stroke, cardiovascular death, heart failure hospitalization, and revascularization, respectively.

Median hemoglobin A_1c values at the end of ORIGIN and at the end of ORIGINALE were 6.3% and 6.6%, respectively, in the 2,351 patients treated with insulin glargine, and 6.52% and 6.70% in the 3,267 patients in the standard-care arm.

Likewise, analysis showed a neutral effect on cancer incidence and cancer death between the insulin and standard-care groups.

There was a trend toward fewer new cases of diabetes among insulin-treated patients than in the standard-care group (37.7% vs. 41.7%; P = .12), with fewer new and possible diabetes cases if insulin was received (41.2% vs. 47.7%; P = .014). The latter included patients who could not be confirmed as having diabetes by adjudication criteria.

In an interview, Dr. Gerstein commented that the findings are reassuring for people at high cardiovascular risk with impaired fasting glucose, impaired glucose tolerance, or early type 2 diabetes who are in need of insulin therapy.

“Insulin is a safe and effective drug, we can use it to lower patients’ glucose levels, and it’s not going to do anything else,” he said. “We have to make sure we use it correctly to avoid hypoglycemia, but there are no hidden perils, at least based on what we know now, and close to 10 years of follow-up.”

Regarding the value of omega-3 fatty acid supplementation, also studied in ORIGIN, the results of ORIGINALE showed no effect on any outcome. “All of the evidence around the world shows that if you take an omega-3 fatty acid capsule, you have no difference in your health outcomes than if you do not,” he said. “All you do is create expensive urine. You do not do anything else with respect to your health.”

Sanofi provided funding for the study, which was coordinated by the Population Health Research Institute in Hamilton. Dr. Gerstein has received research support and adviser fees from Sanofi, Novartis, and other companies.

VIENNA – There is no increased risk for myocardial infarction or other vascular events from prolonged use of insulin in people with pre- or type 2 diabetes who are already at high risk for cardiovascular disease, according to additional follow-up data from the ORIGIN study.

The ORIGINALE (Origin and Legacy Effects) study provides an additional 2.5 years of observational follow-up of more than 8,000 of the 12,000-plus individuals who participated in the ORIGIN (Outcome Reduction with an Initial Glargine Intervention) study.

© iStock/ThinkStockPhotos

The results of the ORIGIN trial were that 6.2 years of treatment with insulin glargine (Sanofi’s Lantus) had a neutral effect on cardiovascular events and other serious health outcomes such as cancer, and possibly slowed diabetes progression (N. Engl. J. Med. 2012;367:319-28). In addition, omega-3 fatty acid supplementation was found to offer no benefit over placebo.

The results of the ORIGINALE study continue to support these findings, Dr. Hertzel C. Gerstein reported at the annual meeting of the European Society for the Study of Diabetes.

The key conclusion of ORIGIN and ORIGINALE with regard to insulin use is that “targeting a normal fasting plasma glucose with basal insulin glargine for more than 6 years improves metabolic status and has a neutral effect on serious health outcomes,” Dr. Gerstein of McMaster University, Hamilton, Ont., observed.

Two coprimary composite cardiovascular outcomes were assessed, neither of which showed any advantage or disadvantage of using insulin glargine versus standard care.

The hazard ratio for the first coprimary outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in ORIGINALE was 1.01, and the HR for the second coprimary endpoint of any cardiovascular event, a revascularization procedure, or hospitalization for heart failure was 1.03.

There was also a “neutral effect” on the individual components of these composite endpoints, with HRs of 1.02, 1.05, 1.00, 0.90, and 1.04 for myocardial infarction, stroke, cardiovascular death, heart failure hospitalization, and revascularization, respectively.

Median hemoglobin A_1c values at the end of ORIGIN and at the end of ORIGINALE were 6.3% and 6.6%, respectively, in the 2,351 patients treated with insulin glargine, and 6.52% and 6.70% in the 3,267 patients in the standard-care arm.

Likewise, analysis showed a neutral effect on cancer incidence and cancer death between the insulin and standard-care groups.

There was a trend toward fewer new cases of diabetes among insulin-treated patients than in the standard-care group (37.7% vs. 41.7%; P = .12), with fewer new and possible diabetes cases if insulin was received (41.2% vs. 47.7%; P = .014). The latter included patients who could not be confirmed as having diabetes by adjudication criteria.

In an interview, Dr. Gerstein commented that the findings are reassuring for people at high cardiovascular risk with impaired fasting glucose, impaired glucose tolerance, or early type 2 diabetes who are in need of insulin therapy.

“Insulin is a safe and effective drug, we can use it to lower patients’ glucose levels, and it’s not going to do anything else,” he said. “We have to make sure we use it correctly to avoid hypoglycemia, but there are no hidden perils, at least based on what we know now, and close to 10 years of follow-up.”

Regarding the value of omega-3 fatty acid supplementation, also studied in ORIGIN, the results of ORIGINALE showed no effect on any outcome. “All of the evidence around the world shows that if you take an omega-3 fatty acid capsule, you have no difference in your health outcomes than if you do not,” he said. “All you do is create expensive urine. You do not do anything else with respect to your health.”

Sanofi provided funding for the study, which was coordinated by the Population Health Research Institute in Hamilton. Dr. Gerstein has received research support and adviser fees from Sanofi, Novartis, and other companies.

VIENNA – There is no increased risk for myocardial infarction or other vascular events from prolonged use of insulin in people with pre- or type 2 diabetes who are already at high risk for cardiovascular disease, according to additional follow-up data from the ORIGIN study.

The ORIGINALE (Origin and Legacy Effects) study provides an additional 2.5 years of observational follow-up of more than 8,000 of the 12,000-plus individuals who participated in the ORIGIN (Outcome Reduction with an Initial Glargine Intervention) study.

© iStock/ThinkStockPhotos

The results of the ORIGIN trial were that 6.2 years of treatment with insulin glargine (Sanofi’s Lantus) had a neutral effect on cardiovascular events and other serious health outcomes such as cancer, and possibly slowed diabetes progression (N. Engl. J. Med. 2012;367:319-28). In addition, omega-3 fatty acid supplementation was found to offer no benefit over placebo.

The results of the ORIGINALE study continue to support these findings, Dr. Hertzel C. Gerstein reported at the annual meeting of the European Society for the Study of Diabetes.

The key conclusion of ORIGIN and ORIGINALE with regard to insulin use is that “targeting a normal fasting plasma glucose with basal insulin glargine for more than 6 years improves metabolic status and has a neutral effect on serious health outcomes,” Dr. Gerstein of McMaster University, Hamilton, Ont., observed.

Two coprimary composite cardiovascular outcomes were assessed, neither of which showed any advantage or disadvantage of using insulin glargine versus standard care.

The hazard ratio for the first coprimary outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in ORIGINALE was 1.01, and the HR for the second coprimary endpoint of any cardiovascular event, a revascularization procedure, or hospitalization for heart failure was 1.03.

There was also a “neutral effect” on the individual components of these composite endpoints, with HRs of 1.02, 1.05, 1.00, 0.90, and 1.04 for myocardial infarction, stroke, cardiovascular death, heart failure hospitalization, and revascularization, respectively.

Median hemoglobin A_1c values at the end of ORIGIN and at the end of ORIGINALE were 6.3% and 6.6%, respectively, in the 2,351 patients treated with insulin glargine, and 6.52% and 6.70% in the 3,267 patients in the standard-care arm.

Likewise, analysis showed a neutral effect on cancer incidence and cancer death between the insulin and standard-care groups.

There was a trend toward fewer new cases of diabetes among insulin-treated patients than in the standard-care group (37.7% vs. 41.7%; P = .12), with fewer new and possible diabetes cases if insulin was received (41.2% vs. 47.7%; P = .014). The latter included patients who could not be confirmed as having diabetes by adjudication criteria.

In an interview, Dr. Gerstein commented that the findings are reassuring for people at high cardiovascular risk with impaired fasting glucose, impaired glucose tolerance, or early type 2 diabetes who are in need of insulin therapy.

“Insulin is a safe and effective drug, we can use it to lower patients’ glucose levels, and it’s not going to do anything else,” he said. “We have to make sure we use it correctly to avoid hypoglycemia, but there are no hidden perils, at least based on what we know now, and close to 10 years of follow-up.”

Regarding the value of omega-3 fatty acid supplementation, also studied in ORIGIN, the results of ORIGINALE showed no effect on any outcome. “All of the evidence around the world shows that if you take an omega-3 fatty acid capsule, you have no difference in your health outcomes than if you do not,” he said. “All you do is create expensive urine. You do not do anything else with respect to your health.”

Sanofi provided funding for the study, which was coordinated by the Population Health Research Institute in Hamilton. Dr. Gerstein has received research support and adviser fees from Sanofi, Novartis, and other companies.

VIENNA – A novel fixed-dose insulin analogue combination reduced blood glucose levels to a similar degree as a control basal-bolus regimen in patients with type 2 diabetes but just failed to show noninferiority for the primary endpoint in a phase IIIb randomized trial.

The percentage change in hemoglobin A_1c from baseline to week 26 was –1.3% for IDegAsp (Ryzodeg, Novo Nordisk) and –1.5% for the basal-bolus regimen used as the comparator.

IDegAsp is a soluble combination of 70% insulin degludec (Tresiba, Novo Nordisk) and 30% insulin aspart (NovoLog, Novo Nordisk). Unlike other fixed-dose insulins, IDeg and IAsp exist separately in a coformulation.

Although noninferiority was not demonstrated for glycemic control, there was a significant benefit in terms of a lower dose of insulin used (1.11 vs. 1.34 U) and less weight gain, of about 1 kg, with IDegAsp than with the basal-bolus approach. There were also numerically lower rates of confirmed (rate ratio, 0.81) and nocturnal hypoglycemia (RR, 0.80). Both regimens were well tolerated.

“If we are very, very, strict, and as we did not reach noninferiority, we can’t really say anything about anything else,” study investigator Dr. John Cooper of Stavanger (Norway) University Hospital conceded in an interview at the annual meeting of the European Association for the Study of Diabetes. He added, however, “common sense says that it is very close and it looks like it is a useful insulin.”

Patients with type 2 diabetes of at least 6 months duration and who had an HbA_1c of 7%-10% despite being treated with basal insulin with or without oral antidiabetic drugs for at least 3 months were eligible for inclusion in the study.

In all, 274 patients were included, with 138 randomized to twice-daily treatment with IDegAsp and 136 to IDeg once daily plus IAsp two to four times a day. The mean age of the participants was 60 years, the mean HbA_1c at baseline was 8.3%, and the average duration of diabetes was 13 years. The majority (63%) of patients had been treated with insulin glargine prior to study entry.

“IDegAsp twice daily may represent a simple alternative to basal-bolus treatment in patients who require intensification of basal insulin regimens, especially when adherence to more complex regimens is challenging,” Dr. Cooper said at the conclusion of his presentation.

He noted during the discussion that quality of life had been assessed using the Short-Form 36 at the start and end of the trial, and while there were no differences between the regimens in terms of the physical scores, there was a benefit seen in the mental component with IDegAsp that was driven mainly by improvements in social functioning.

“I’ve mainly used basal plus meal-time insulin doses in type 2 diabetes patients, but I might reconsider using the combination, but that’s more on the basis that I know it gives less hypoglycemia, compared with the older, premixed insulins,” Dr. Cooper commented in the postpresentation interview.

The novel insulin formulation could also offer patients who need treatment intensification a more convenient approach to their insulin therapy, he said, rather than having to inject long-acting insulin once daily and short-acting insulin up to four times a day. With IDegAsp, patients could inject just twice a day at major meal times. “This will certainly be a useful addition for some patients,” Dr. Cooper suggested.

To date, IDegAsp has been approved for use in several European, Asian, and South American countries. The Food and Drug Administration, however, has requested additional cardiovascular outcomes data to be obtained before giving market authorization for its use.

The study was funded by Novo Nordisk. Dr. Cooper has received research support and speaker fees from Novo Nordisk, Sanofi, Eli Lilly and Company, Merck, and AstraZeneca, and is a member of a speakers bureau for Novartis.

VIENNA – A novel fixed-dose insulin analogue combination reduced blood glucose levels to a similar degree as a control basal-bolus regimen in patients with type 2 diabetes but just failed to show noninferiority for the primary endpoint in a phase IIIb randomized trial.

The percentage change in hemoglobin A_1c from baseline to week 26 was –1.3% for IDegAsp (Ryzodeg, Novo Nordisk) and –1.5% for the basal-bolus regimen used as the comparator.

IDegAsp is a soluble combination of 70% insulin degludec (Tresiba, Novo Nordisk) and 30% insulin aspart (NovoLog, Novo Nordisk). Unlike other fixed-dose insulins, IDeg and IAsp exist separately in a coformulation.

Although noninferiority was not demonstrated for glycemic control, there was a significant benefit in terms of a lower dose of insulin used (1.11 vs. 1.34 U) and less weight gain, of about 1 kg, with IDegAsp than with the basal-bolus approach. There were also numerically lower rates of confirmed (rate ratio, 0.81) and nocturnal hypoglycemia (RR, 0.80). Both regimens were well tolerated.

“If we are very, very, strict, and as we did not reach noninferiority, we can’t really say anything about anything else,” study investigator Dr. John Cooper of Stavanger (Norway) University Hospital conceded in an interview at the annual meeting of the European Association for the Study of Diabetes. He added, however, “common sense says that it is very close and it looks like it is a useful insulin.”

Patients with type 2 diabetes of at least 6 months duration and who had an HbA_1c of 7%-10% despite being treated with basal insulin with or without oral antidiabetic drugs for at least 3 months were eligible for inclusion in the study.

In all, 274 patients were included, with 138 randomized to twice-daily treatment with IDegAsp and 136 to IDeg once daily plus IAsp two to four times a day. The mean age of the participants was 60 years, the mean HbA_1c at baseline was 8.3%, and the average duration of diabetes was 13 years. The majority (63%) of patients had been treated with insulin glargine prior to study entry.

“IDegAsp twice daily may represent a simple alternative to basal-bolus treatment in patients who require intensification of basal insulin regimens, especially when adherence to more complex regimens is challenging,” Dr. Cooper said at the conclusion of his presentation.

He noted during the discussion that quality of life had been assessed using the Short-Form 36 at the start and end of the trial, and while there were no differences between the regimens in terms of the physical scores, there was a benefit seen in the mental component with IDegAsp that was driven mainly by improvements in social functioning.

“I’ve mainly used basal plus meal-time insulin doses in type 2 diabetes patients, but I might reconsider using the combination, but that’s more on the basis that I know it gives less hypoglycemia, compared with the older, premixed insulins,” Dr. Cooper commented in the postpresentation interview.

The novel insulin formulation could also offer patients who need treatment intensification a more convenient approach to their insulin therapy, he said, rather than having to inject long-acting insulin once daily and short-acting insulin up to four times a day. With IDegAsp, patients could inject just twice a day at major meal times. “This will certainly be a useful addition for some patients,” Dr. Cooper suggested.

To date, IDegAsp has been approved for use in several European, Asian, and South American countries. The Food and Drug Administration, however, has requested additional cardiovascular outcomes data to be obtained before giving market authorization for its use.

The study was funded by Novo Nordisk. Dr. Cooper has received research support and speaker fees from Novo Nordisk, Sanofi, Eli Lilly and Company, Merck, and AstraZeneca, and is a member of a speakers bureau for Novartis.

VIENNA – A novel fixed-dose insulin analogue combination reduced blood glucose levels to a similar degree as a control basal-bolus regimen in patients with type 2 diabetes but just failed to show noninferiority for the primary endpoint in a phase IIIb randomized trial.

The percentage change in hemoglobin A_1c from baseline to week 26 was –1.3% for IDegAsp (Ryzodeg, Novo Nordisk) and –1.5% for the basal-bolus regimen used as the comparator.

IDegAsp is a soluble combination of 70% insulin degludec (Tresiba, Novo Nordisk) and 30% insulin aspart (NovoLog, Novo Nordisk). Unlike other fixed-dose insulins, IDeg and IAsp exist separately in a coformulation.

Although noninferiority was not demonstrated for glycemic control, there was a significant benefit in terms of a lower dose of insulin used (1.11 vs. 1.34 U) and less weight gain, of about 1 kg, with IDegAsp than with the basal-bolus approach. There were also numerically lower rates of confirmed (rate ratio, 0.81) and nocturnal hypoglycemia (RR, 0.80). Both regimens were well tolerated.

“If we are very, very, strict, and as we did not reach noninferiority, we can’t really say anything about anything else,” study investigator Dr. John Cooper of Stavanger (Norway) University Hospital conceded in an interview at the annual meeting of the European Association for the Study of Diabetes. He added, however, “common sense says that it is very close and it looks like it is a useful insulin.”

Patients with type 2 diabetes of at least 6 months duration and who had an HbA_1c of 7%-10% despite being treated with basal insulin with or without oral antidiabetic drugs for at least 3 months were eligible for inclusion in the study.

In all, 274 patients were included, with 138 randomized to twice-daily treatment with IDegAsp and 136 to IDeg once daily plus IAsp two to four times a day. The mean age of the participants was 60 years, the mean HbA_1c at baseline was 8.3%, and the average duration of diabetes was 13 years. The majority (63%) of patients had been treated with insulin glargine prior to study entry.

“IDegAsp twice daily may represent a simple alternative to basal-bolus treatment in patients who require intensification of basal insulin regimens, especially when adherence to more complex regimens is challenging,” Dr. Cooper said at the conclusion of his presentation.

He noted during the discussion that quality of life had been assessed using the Short-Form 36 at the start and end of the trial, and while there were no differences between the regimens in terms of the physical scores, there was a benefit seen in the mental component with IDegAsp that was driven mainly by improvements in social functioning.

“I’ve mainly used basal plus meal-time insulin doses in type 2 diabetes patients, but I might reconsider using the combination, but that’s more on the basis that I know it gives less hypoglycemia, compared with the older, premixed insulins,” Dr. Cooper commented in the postpresentation interview.

The novel insulin formulation could also offer patients who need treatment intensification a more convenient approach to their insulin therapy, he said, rather than having to inject long-acting insulin once daily and short-acting insulin up to four times a day. With IDegAsp, patients could inject just twice a day at major meal times. “This will certainly be a useful addition for some patients,” Dr. Cooper suggested.

To date, IDegAsp has been approved for use in several European, Asian, and South American countries. The Food and Drug Administration, however, has requested additional cardiovascular outcomes data to be obtained before giving market authorization for its use.

The study was funded by Novo Nordisk. Dr. Cooper has received research support and speaker fees from Novo Nordisk, Sanofi, Eli Lilly and Company, Merck, and AstraZeneca, and is a member of a speakers bureau for Novartis.

Dulaglutide, a glucagon-like peptide-1 receptor agonist administered subcutaneously once a week, has been approved for treatment of adults with type 2 diabetes, the Food and Drug Administration announced Sept. 18.

It was approved with a Risk Evaluation and Mitigation Strategy (REMS) aimed at informing health care professionals about the serious risks of treatment and requirements for postmarketing studies that address some of those risks, the FDA said in a statement.

Approval was based on six studies of about 3,300 patients with type 2 diabetes who were treated with dulaglutide as monotherapy, and in combination with other approved type 2 diabetes treatments, including metformin. It will be marketed as Trulicity by Eli Lilly.

The drug’s label has a boxed warning that thyroid C-cell tumors have been observed in rodent studies of dulaglutide, “but that it is unknown whether Trulicity causes thyroid C-cell tumors,” including medullary thyroid carcinoma (MTC) in humans, the statement said. It should not be used to treat patients who have had, or have, a family history of MTC, or in patients who have multiple endocrine neoplasia syndrome type 2, who are predisposed to MTC, the statement noted.

Eli Lilly is required to conduct several postmarketing studies, including a cardiovascular outcomes study in patients at a high risk of cardiovascular disease at baseline, a pediatric study, and a registry study of MTC cases to help determine whether there is an increase in the incidence of MTC associated with the use of the drug, for at least 15 years. Another postmarketing study will compare dulaglutide to insulin glargine for glycemic control in patients with type 2 diabetes and moderate or severe renal impairment.

[email protected]

Dulaglutide, a glucagon-like peptide-1 receptor agonist administered subcutaneously once a week, has been approved for treatment of adults with type 2 diabetes, the Food and Drug Administration announced Sept. 18.

It was approved with a Risk Evaluation and Mitigation Strategy (REMS) aimed at informing health care professionals about the serious risks of treatment and requirements for postmarketing studies that address some of those risks, the FDA said in a statement.

Approval was based on six studies of about 3,300 patients with type 2 diabetes who were treated with dulaglutide as monotherapy, and in combination with other approved type 2 diabetes treatments, including metformin. It will be marketed as Trulicity by Eli Lilly.

The drug’s label has a boxed warning that thyroid C-cell tumors have been observed in rodent studies of dulaglutide, “but that it is unknown whether Trulicity causes thyroid C-cell tumors,” including medullary thyroid carcinoma (MTC) in humans, the statement said. It should not be used to treat patients who have had, or have, a family history of MTC, or in patients who have multiple endocrine neoplasia syndrome type 2, who are predisposed to MTC, the statement noted.

Eli Lilly is required to conduct several postmarketing studies, including a cardiovascular outcomes study in patients at a high risk of cardiovascular disease at baseline, a pediatric study, and a registry study of MTC cases to help determine whether there is an increase in the incidence of MTC associated with the use of the drug, for at least 15 years. Another postmarketing study will compare dulaglutide to insulin glargine for glycemic control in patients with type 2 diabetes and moderate or severe renal impairment.

[email protected]

Dulaglutide, a glucagon-like peptide-1 receptor agonist administered subcutaneously once a week, has been approved for treatment of adults with type 2 diabetes, the Food and Drug Administration announced Sept. 18.

It was approved with a Risk Evaluation and Mitigation Strategy (REMS) aimed at informing health care professionals about the serious risks of treatment and requirements for postmarketing studies that address some of those risks, the FDA said in a statement.

Approval was based on six studies of about 3,300 patients with type 2 diabetes who were treated with dulaglutide as monotherapy, and in combination with other approved type 2 diabetes treatments, including metformin. It will be marketed as Trulicity by Eli Lilly.

The drug’s label has a boxed warning that thyroid C-cell tumors have been observed in rodent studies of dulaglutide, “but that it is unknown whether Trulicity causes thyroid C-cell tumors,” including medullary thyroid carcinoma (MTC) in humans, the statement said. It should not be used to treat patients who have had, or have, a family history of MTC, or in patients who have multiple endocrine neoplasia syndrome type 2, who are predisposed to MTC, the statement noted.

Eli Lilly is required to conduct several postmarketing studies, including a cardiovascular outcomes study in patients at a high risk of cardiovascular disease at baseline, a pediatric study, and a registry study of MTC cases to help determine whether there is an increase in the incidence of MTC associated with the use of the drug, for at least 15 years. Another postmarketing study will compare dulaglutide to insulin glargine for glycemic control in patients with type 2 diabetes and moderate or severe renal impairment.

[email protected]

VIENNA – A web-based program halved the number of driving incidents experienced by patients with type 1 diabetes deemed at high risk for motoring accidents in a randomized trial.

The annual rate of driving mishaps was around 6 for diabetic drivers identified as being at high risk of future “driving mishaps” and who were randomized to the novel Internet intervention in addition to their routine care, compared with 3 for those at high risk who received usual care.

“Driving mishaps included collisions and moving vehicle violations,” said study investigator Daniel Cox, Ph.D., at the annual meeting of the European Association for the Study of Diabetes.

©Michael Shake/Fotolia.com

Dr. Cox, a clinical psychologist at the University of Virginia, Charlottesville, added that driving mishaps also included any event that could lead to a collision, such as severe hypoglycemia, someone else having to take control of the car, automatic driving, unintentionally stopping driving, and losing control of the vehicle but not actually hitting anything.

Participants were identified as being at high risk of future diabetes-related driving incidents using the 11-item Risk Assessment for Diabetic Drivers (RADD) questionnaire, which was developed by the investigators on the basis of responses from 500 individuals to questions on driving exposure, diabetes control, and the frequency of driving mishaps over the course of a year.

Peripheral neuropathy in the lower limbs was the most potent predictor of future driving mishaps, while hypoglycemia unawareness did not really rank, Dr. Cox observed, adding that RADD had 61% sensitivity and 75% specificity to differentiate diabetic drivers at high and low risk of a future driving mishap.

The study involved screening more than 1,700 drivers with type 1 diabetes who had registered with DiabetesDriving.com. Of these, 122 were identified via RADD as being at low risk of future driving mishaps and were included as a control group, while 379 were identified as being at high risk and were randomized to one of three groups: The first group continued to receive routine care, the second received the intervention in addition to routine care, and the third received the Internet intervention, routine care, and motivational interviewing conducted by telephone before and after using the web-based program.

At baseline, all participants underwent psychometric testing, and then they completed the intervention over a 2-month period. They were then asked to complete monthly online diaries to document any driving mishaps that may have occurred.

DiabetesDriving.com is an interactive, Internet intervention based on active learning. There are five sections to the program. The first provides participants with an overview on how to use a simple diabetes ‘tool kit’, which consists of a series of items contained in a plastic bag to keep in the car. Items in the kit include a key chain with a traffic light system giving guidance on blood glucose levels and whether it is safe to drive or not, a predrive checklist, a glucose meter, a fast-acting dextrose preparation, long-acting carbohydrates in the form of cheese crackers, and a car sticker to alert authorities in the event of a driving mishap.

Other sections of the program cover general issues on diabetes and driving, and how to detect, prevent, and manage extreme blood glucose levels while driving. The final section focuses on how safer driving habits can be sustained in the long term.

Results showed that RADD could be used to distinguish patients with type 1 diabetes at low and high risk of driving mishaps, with the latter having 258% more driving incidents than the former, a statistically significant difference. The basic demographics (i.e., age and gender) and the use of continuous glucose monitoring devices were similar between high- and low-risk patients.

There were 53% fewer driving mishaps among the high-risk diabetic drivers who underwent the intervention, compared with those who did not, Dr. Cox reported. “Motivational interviewing did not significantly influence the outcome,” he reported, and so the additional costs of this cannot be justified in this setting.

Interestingly, it did not seem to matter if drivers completed the whole program or just some of the sections. That said, completing the first section of the program was the most important element overall.

Drivers at high risk for driving mishaps can reduce future mishaps by using DiabetesDriving.com, Dr. Cox concluded. There is now a need to improve RADD’s sensitivity and specificity and to optimize the intervention, he added, which would help with the wider dissemination and use of the program in the diabetes community.

The National Institutes of Health funded the study, and Lifescan, Abbott, and Dex4 provided supplies, including glucose monitors and a fast-acting glucose. Dr. Cox and his coinvestigators had no conflicts of interest.

VIENNA – A web-based program halved the number of driving incidents experienced by patients with type 1 diabetes deemed at high risk for motoring accidents in a randomized trial.

The annual rate of driving mishaps was around 6 for diabetic drivers identified as being at high risk of future “driving mishaps” and who were randomized to the novel Internet intervention in addition to their routine care, compared with 3 for those at high risk who received usual care.

“Driving mishaps included collisions and moving vehicle violations,” said study investigator Daniel Cox, Ph.D., at the annual meeting of the European Association for the Study of Diabetes.

©Michael Shake/Fotolia.com

Dr. Cox, a clinical psychologist at the University of Virginia, Charlottesville, added that driving mishaps also included any event that could lead to a collision, such as severe hypoglycemia, someone else having to take control of the car, automatic driving, unintentionally stopping driving, and losing control of the vehicle but not actually hitting anything.

Participants were identified as being at high risk of future diabetes-related driving incidents using the 11-item Risk Assessment for Diabetic Drivers (RADD) questionnaire, which was developed by the investigators on the basis of responses from 500 individuals to questions on driving exposure, diabetes control, and the frequency of driving mishaps over the course of a year.

Peripheral neuropathy in the lower limbs was the most potent predictor of future driving mishaps, while hypoglycemia unawareness did not really rank, Dr. Cox observed, adding that RADD had 61% sensitivity and 75% specificity to differentiate diabetic drivers at high and low risk of a future driving mishap.

The study involved screening more than 1,700 drivers with type 1 diabetes who had registered with DiabetesDriving.com. Of these, 122 were identified via RADD as being at low risk of future driving mishaps and were included as a control group, while 379 were identified as being at high risk and were randomized to one of three groups: The first group continued to receive routine care, the second received the intervention in addition to routine care, and the third received the Internet intervention, routine care, and motivational interviewing conducted by telephone before and after using the web-based program.

At baseline, all participants underwent psychometric testing, and then they completed the intervention over a 2-month period. They were then asked to complete monthly online diaries to document any driving mishaps that may have occurred.

DiabetesDriving.com is an interactive, Internet intervention based on active learning. There are five sections to the program. The first provides participants with an overview on how to use a simple diabetes ‘tool kit’, which consists of a series of items contained in a plastic bag to keep in the car. Items in the kit include a key chain with a traffic light system giving guidance on blood glucose levels and whether it is safe to drive or not, a predrive checklist, a glucose meter, a fast-acting dextrose preparation, long-acting carbohydrates in the form of cheese crackers, and a car sticker to alert authorities in the event of a driving mishap.

Other sections of the program cover general issues on diabetes and driving, and how to detect, prevent, and manage extreme blood glucose levels while driving. The final section focuses on how safer driving habits can be sustained in the long term.

Results showed that RADD could be used to distinguish patients with type 1 diabetes at low and high risk of driving mishaps, with the latter having 258% more driving incidents than the former, a statistically significant difference. The basic demographics (i.e., age and gender) and the use of continuous glucose monitoring devices were similar between high- and low-risk patients.

There were 53% fewer driving mishaps among the high-risk diabetic drivers who underwent the intervention, compared with those who did not, Dr. Cox reported. “Motivational interviewing did not significantly influence the outcome,” he reported, and so the additional costs of this cannot be justified in this setting.

Interestingly, it did not seem to matter if drivers completed the whole program or just some of the sections. That said, completing the first section of the program was the most important element overall.

Drivers at high risk for driving mishaps can reduce future mishaps by using DiabetesDriving.com, Dr. Cox concluded. There is now a need to improve RADD’s sensitivity and specificity and to optimize the intervention, he added, which would help with the wider dissemination and use of the program in the diabetes community.

The National Institutes of Health funded the study, and Lifescan, Abbott, and Dex4 provided supplies, including glucose monitors and a fast-acting glucose. Dr. Cox and his coinvestigators had no conflicts of interest.

VIENNA – A web-based program halved the number of driving incidents experienced by patients with type 1 diabetes deemed at high risk for motoring accidents in a randomized trial.

The annual rate of driving mishaps was around 6 for diabetic drivers identified as being at high risk of future “driving mishaps” and who were randomized to the novel Internet intervention in addition to their routine care, compared with 3 for those at high risk who received usual care.

“Driving mishaps included collisions and moving vehicle violations,” said study investigator Daniel Cox, Ph.D., at the annual meeting of the European Association for the Study of Diabetes.

©Michael Shake/Fotolia.com

Dr. Cox, a clinical psychologist at the University of Virginia, Charlottesville, added that driving mishaps also included any event that could lead to a collision, such as severe hypoglycemia, someone else having to take control of the car, automatic driving, unintentionally stopping driving, and losing control of the vehicle but not actually hitting anything.

Participants were identified as being at high risk of future diabetes-related driving incidents using the 11-item Risk Assessment for Diabetic Drivers (RADD) questionnaire, which was developed by the investigators on the basis of responses from 500 individuals to questions on driving exposure, diabetes control, and the frequency of driving mishaps over the course of a year.

Peripheral neuropathy in the lower limbs was the most potent predictor of future driving mishaps, while hypoglycemia unawareness did not really rank, Dr. Cox observed, adding that RADD had 61% sensitivity and 75% specificity to differentiate diabetic drivers at high and low risk of a future driving mishap.

The study involved screening more than 1,700 drivers with type 1 diabetes who had registered with DiabetesDriving.com. Of these, 122 were identified via RADD as being at low risk of future driving mishaps and were included as a control group, while 379 were identified as being at high risk and were randomized to one of three groups: The first group continued to receive routine care, the second received the intervention in addition to routine care, and the third received the Internet intervention, routine care, and motivational interviewing conducted by telephone before and after using the web-based program.

At baseline, all participants underwent psychometric testing, and then they completed the intervention over a 2-month period. They were then asked to complete monthly online diaries to document any driving mishaps that may have occurred.

DiabetesDriving.com is an interactive, Internet intervention based on active learning. There are five sections to the program. The first provides participants with an overview on how to use a simple diabetes ‘tool kit’, which consists of a series of items contained in a plastic bag to keep in the car. Items in the kit include a key chain with a traffic light system giving guidance on blood glucose levels and whether it is safe to drive or not, a predrive checklist, a glucose meter, a fast-acting dextrose preparation, long-acting carbohydrates in the form of cheese crackers, and a car sticker to alert authorities in the event of a driving mishap.

Other sections of the program cover general issues on diabetes and driving, and how to detect, prevent, and manage extreme blood glucose levels while driving. The final section focuses on how safer driving habits can be sustained in the long term.

Results showed that RADD could be used to distinguish patients with type 1 diabetes at low and high risk of driving mishaps, with the latter having 258% more driving incidents than the former, a statistically significant difference. The basic demographics (i.e., age and gender) and the use of continuous glucose monitoring devices were similar between high- and low-risk patients.

There were 53% fewer driving mishaps among the high-risk diabetic drivers who underwent the intervention, compared with those who did not, Dr. Cox reported. “Motivational interviewing did not significantly influence the outcome,” he reported, and so the additional costs of this cannot be justified in this setting.

Interestingly, it did not seem to matter if drivers completed the whole program or just some of the sections. That said, completing the first section of the program was the most important element overall.

Drivers at high risk for driving mishaps can reduce future mishaps by using DiabetesDriving.com, Dr. Cox concluded. There is now a need to improve RADD’s sensitivity and specificity and to optimize the intervention, he added, which would help with the wider dissemination and use of the program in the diabetes community.

The National Institutes of Health funded the study, and Lifescan, Abbott, and Dex4 provided supplies, including glucose monitors and a fast-acting glucose. Dr. Cox and his coinvestigators had no conflicts of interest.

VIENNA – Although several new oral hypoglycemic drug classes have entered formularies over the past 5 years or so, none has supplanted insulin as a linchpin for managing patients with type 2 diabetes who fail to achieve adequate glycemic control with diet, exercise, and metformin treatment, Dr. David M. Nathan said in an interview during the annual meeting of the European Association for the Study of Diabetes.

Physicians should keep in mind that insulin remains a “powerful and important drug” for type 2 patients, said Dr. Nathan, chief of diabetes at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston. Even though insulin’s price has risen recently, it is still a bargain, compared with the new drugs, he added.

Dr. Nathan said he had no relevant financial disclosures.

[email protected]

On Twitter @mitchelzoler

VIENNA – Although several new oral hypoglycemic drug classes have entered formularies over the past 5 years or so, none has supplanted insulin as a linchpin for managing patients with type 2 diabetes who fail to achieve adequate glycemic control with diet, exercise, and metformin treatment, Dr. David M. Nathan said in an interview during the annual meeting of the European Association for the Study of Diabetes.

Physicians should keep in mind that insulin remains a “powerful and important drug” for type 2 patients, said Dr. Nathan, chief of diabetes at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston. Even though insulin’s price has risen recently, it is still a bargain, compared with the new drugs, he added.

Dr. Nathan said he had no relevant financial disclosures.

[email protected]

On Twitter @mitchelzoler

VIENNA – Although several new oral hypoglycemic drug classes have entered formularies over the past 5 years or so, none has supplanted insulin as a linchpin for managing patients with type 2 diabetes who fail to achieve adequate glycemic control with diet, exercise, and metformin treatment, Dr. David M. Nathan said in an interview during the annual meeting of the European Association for the Study of Diabetes.

Physicians should keep in mind that insulin remains a “powerful and important drug” for type 2 patients, said Dr. Nathan, chief of diabetes at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston. Even though insulin’s price has risen recently, it is still a bargain, compared with the new drugs, he added.

Dr. Nathan said he had no relevant financial disclosures.

[email protected]

On Twitter @mitchelzoler

VIENNA – Adding agents from two relatively new oral hypoglycemic drug classes to metformin produced a rapid, incremental reduction in hemoglobin A_1c of more than 1% in two separate, phase III randomized controlled trials of patients with type 2 diabetes.

The efficacy and safety shown in the studies raises the possibility of formulating such three-agent combinations into single-pills, said Dr. Ralph A. DeFronzo, lead investigator for one of the studies.

The results “open the way to thinking about triple combinations. The next step is to concoct a single tablet with all three drugs together,” said Dr. DeFronzo at the annual meeting of the European Association for the Study of Diabetes.

The concept of treating patients with type 2 diabetes who fail to receive adequate glycemic control from diet and metformin treatment with the simultaneous addition of a drug from the sodium-glucose co-transporter 2 (SGLT-2) inhibitors class and a drug from the dipeptidyl peptidase-4 (DPP-4) inhibitor class “represents a new, proactive treatment paradigm, and appears to be an attractive option to safely and effectively bring difficult-to-treat metformin-failure patients to individualized glycemic goals,” said Dr. Julio Rosenstock, lead investigator for the second reported study and an endocrinologist at the University of Texas Southwestern Medical Center.

The study results reported by Dr. DeFronzo came from 677 patients with a HbA_1c level of 7%-10% despite treatment with a stable metformin regimen for at least 12 weeks. Patients averaged about 56 years of age, and about three-quarters had been diagnosed with diabetes for more than 5 years. The researchers maintained all patients on their metformin dosage and randomized them to any of five treatment arms: 10 mg daily of the SGLT2 inhibitor empagliflozin (Jardiance), 25 mg daily empagliflozin, 5 mg daily of the DPP-4 inhibitor linagliptin (Trajenta), and two combination regimens: 5 mg linagliptin and 10 mg empagliflozin, and 5 mg linagliptin and 25 mg empagliflozin. The study’s primary endpoint was change from baseline in HbA_1c after 24 weeks on treatment.

The results showed and average 1.19% drop in _HbA1c after 24 weeks in patients on triple treatment with the higher dosage of empagliflozin, a 1.08% reduction in patients on the lower-dose, triple-treatment combination, and reductions that ranged from 0.62%-0.70% among the patients who received just one drug added to metformin. The differences between patients on either triple regimen and those on the three different dual regimens were statistically significant.

“Clearly, the combinations [of empagliflozin and linagliptin] have a greater effect than either of the drugs alone, but the effect is not completely additive,” noted Dr. DeFronzo, professor and chief of diabetes at the University of Texas Health Science Center, San Antonio.

The results also showed an average reduction in systolic blood pressure of 3-4 mm Hg among patients on triple therapy, similar to the effect from adding empagliflozin alone. The triple combinations were well tolerated, with a safety profile similar to monotherapy with these approved drugs, and confirmed hypoglycemia rates of 2%-4%, also similar to the rates seen with these drugs when used singly in combination with metformin.

The second study randomized 534 patients with a HbA_1c level of 8%-12% while on stable metformin treatment. They averaged 53 years of age and had an average HbA_1c of 8.9%. In addition to remaining on metformin, the researchers assigned patients to receive 10 mg of dapagliflozin (Farxiga) daily, 5 mg saxagliptin (Onglyza) daily, or a regimen that included all three drugs.

After 24 weeks on treatment, patients on the triple-drug regimen had an average reduction in HbA_1c of 1.5%, while those on dapagliflozin plus metformin averaged a 1.2% reduction, while those on saxagliptin plus metformin had an average 0.9% drop. The differences between the triple-drug group and each of the two-drug groups were statistically significant for the study’s primary endpoint. The percentage of patients who achieved a HbA_1c of less than 7% was 41% for patients on all three drugs, 22% for those on dapagliflozin plus metformin, and 18% for those on saxagliptin and metformin.

Patients on all three drugs also showed weight loss and blood pressure reductions roughly similar to the higher rates seen in the two control arms. The triple regimen was also well tolerated, with one patient having a minor hypoglycemic episode.

The empagliflozin and linagliptin study was sponsored by Boehringer Ingelheim, which markets both drugs. The dapagliflozin plus saxagliptin study was sponsored by Bristol-Myers Squibb and AstraZeneca, which market both drugs. Dr. DeFronzo is an adviser to and speaker for Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, and other drug companies. Dr. Rosenstock is a consultant to Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, and other drug companies.

[email protected]

On Twitter @mitchelzoler

VIENNA – Adding agents from two relatively new oral hypoglycemic drug classes to metformin produced a rapid, incremental reduction in hemoglobin A_1c of more than 1% in two separate, phase III randomized controlled trials of patients with type 2 diabetes.

The efficacy and safety shown in the studies raises the possibility of formulating such three-agent combinations into single-pills, said Dr. Ralph A. DeFronzo, lead investigator for one of the studies.

The results “open the way to thinking about triple combinations. The next step is to concoct a single tablet with all three drugs together,” said Dr. DeFronzo at the annual meeting of the European Association for the Study of Diabetes.

The concept of treating patients with type 2 diabetes who fail to receive adequate glycemic control from diet and metformin treatment with the simultaneous addition of a drug from the sodium-glucose co-transporter 2 (SGLT-2) inhibitors class and a drug from the dipeptidyl peptidase-4 (DPP-4) inhibitor class “represents a new, proactive treatment paradigm, and appears to be an attractive option to safely and effectively bring difficult-to-treat metformin-failure patients to individualized glycemic goals,” said Dr. Julio Rosenstock, lead investigator for the second reported study and an endocrinologist at the University of Texas Southwestern Medical Center.

The study results reported by Dr. DeFronzo came from 677 patients with a HbA_1c level of 7%-10% despite treatment with a stable metformin regimen for at least 12 weeks. Patients averaged about 56 years of age, and about three-quarters had been diagnosed with diabetes for more than 5 years. The researchers maintained all patients on their metformin dosage and randomized them to any of five treatment arms: 10 mg daily of the SGLT2 inhibitor empagliflozin (Jardiance), 25 mg daily empagliflozin, 5 mg daily of the DPP-4 inhibitor linagliptin (Trajenta), and two combination regimens: 5 mg linagliptin and 10 mg empagliflozin, and 5 mg linagliptin and 25 mg empagliflozin. The study’s primary endpoint was change from baseline in HbA_1c after 24 weeks on treatment.

The results showed and average 1.19% drop in _HbA1c after 24 weeks in patients on triple treatment with the higher dosage of empagliflozin, a 1.08% reduction in patients on the lower-dose, triple-treatment combination, and reductions that ranged from 0.62%-0.70% among the patients who received just one drug added to metformin. The differences between patients on either triple regimen and those on the three different dual regimens were statistically significant.

“Clearly, the combinations [of empagliflozin and linagliptin] have a greater effect than either of the drugs alone, but the effect is not completely additive,” noted Dr. DeFronzo, professor and chief of diabetes at the University of Texas Health Science Center, San Antonio.

The results also showed an average reduction in systolic blood pressure of 3-4 mm Hg among patients on triple therapy, similar to the effect from adding empagliflozin alone. The triple combinations were well tolerated, with a safety profile similar to monotherapy with these approved drugs, and confirmed hypoglycemia rates of 2%-4%, also similar to the rates seen with these drugs when used singly in combination with metformin.

The second study randomized 534 patients with a HbA_1c level of 8%-12% while on stable metformin treatment. They averaged 53 years of age and had an average HbA_1c of 8.9%. In addition to remaining on metformin, the researchers assigned patients to receive 10 mg of dapagliflozin (Farxiga) daily, 5 mg saxagliptin (Onglyza) daily, or a regimen that included all three drugs.

After 24 weeks on treatment, patients on the triple-drug regimen had an average reduction in HbA_1c of 1.5%, while those on dapagliflozin plus metformin averaged a 1.2% reduction, while those on saxagliptin plus metformin had an average 0.9% drop. The differences between the triple-drug group and each of the two-drug groups were statistically significant for the study’s primary endpoint. The percentage of patients who achieved a HbA_1c of less than 7% was 41% for patients on all three drugs, 22% for those on dapagliflozin plus metformin, and 18% for those on saxagliptin and metformin.

Patients on all three drugs also showed weight loss and blood pressure reductions roughly similar to the higher rates seen in the two control arms. The triple regimen was also well tolerated, with one patient having a minor hypoglycemic episode.

The empagliflozin and linagliptin study was sponsored by Boehringer Ingelheim, which markets both drugs. The dapagliflozin plus saxagliptin study was sponsored by Bristol-Myers Squibb and AstraZeneca, which market both drugs. Dr. DeFronzo is an adviser to and speaker for Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, and other drug companies. Dr. Rosenstock is a consultant to Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, and other drug companies.

[email protected]

On Twitter @mitchelzoler

VIENNA – Adding agents from two relatively new oral hypoglycemic drug classes to metformin produced a rapid, incremental reduction in hemoglobin A_1c of more than 1% in two separate, phase III randomized controlled trials of patients with type 2 diabetes.

The efficacy and safety shown in the studies raises the possibility of formulating such three-agent combinations into single-pills, said Dr. Ralph A. DeFronzo, lead investigator for one of the studies.

The results “open the way to thinking about triple combinations. The next step is to concoct a single tablet with all three drugs together,” said Dr. DeFronzo at the annual meeting of the European Association for the Study of Diabetes.

The concept of treating patients with type 2 diabetes who fail to receive adequate glycemic control from diet and metformin treatment with the simultaneous addition of a drug from the sodium-glucose co-transporter 2 (SGLT-2) inhibitors class and a drug from the dipeptidyl peptidase-4 (DPP-4) inhibitor class “represents a new, proactive treatment paradigm, and appears to be an attractive option to safely and effectively bring difficult-to-treat metformin-failure patients to individualized glycemic goals,” said Dr. Julio Rosenstock, lead investigator for the second reported study and an endocrinologist at the University of Texas Southwestern Medical Center.

The study results reported by Dr. DeFronzo came from 677 patients with a HbA_1c level of 7%-10% despite treatment with a stable metformin regimen for at least 12 weeks. Patients averaged about 56 years of age, and about three-quarters had been diagnosed with diabetes for more than 5 years. The researchers maintained all patients on their metformin dosage and randomized them to any of five treatment arms: 10 mg daily of the SGLT2 inhibitor empagliflozin (Jardiance), 25 mg daily empagliflozin, 5 mg daily of the DPP-4 inhibitor linagliptin (Trajenta), and two combination regimens: 5 mg linagliptin and 10 mg empagliflozin, and 5 mg linagliptin and 25 mg empagliflozin. The study’s primary endpoint was change from baseline in HbA_1c after 24 weeks on treatment.

The results showed and average 1.19% drop in _HbA1c after 24 weeks in patients on triple treatment with the higher dosage of empagliflozin, a 1.08% reduction in patients on the lower-dose, triple-treatment combination, and reductions that ranged from 0.62%-0.70% among the patients who received just one drug added to metformin. The differences between patients on either triple regimen and those on the three different dual regimens were statistically significant.

“Clearly, the combinations [of empagliflozin and linagliptin] have a greater effect than either of the drugs alone, but the effect is not completely additive,” noted Dr. DeFronzo, professor and chief of diabetes at the University of Texas Health Science Center, San Antonio.

The results also showed an average reduction in systolic blood pressure of 3-4 mm Hg among patients on triple therapy, similar to the effect from adding empagliflozin alone. The triple combinations were well tolerated, with a safety profile similar to monotherapy with these approved drugs, and confirmed hypoglycemia rates of 2%-4%, also similar to the rates seen with these drugs when used singly in combination with metformin.

The second study randomized 534 patients with a HbA_1c level of 8%-12% while on stable metformin treatment. They averaged 53 years of age and had an average HbA_1c of 8.9%. In addition to remaining on metformin, the researchers assigned patients to receive 10 mg of dapagliflozin (Farxiga) daily, 5 mg saxagliptin (Onglyza) daily, or a regimen that included all three drugs.

After 24 weeks on treatment, patients on the triple-drug regimen had an average reduction in HbA_1c of 1.5%, while those on dapagliflozin plus metformin averaged a 1.2% reduction, while those on saxagliptin plus metformin had an average 0.9% drop. The differences between the triple-drug group and each of the two-drug groups were statistically significant for the study’s primary endpoint. The percentage of patients who achieved a HbA_1c of less than 7% was 41% for patients on all three drugs, 22% for those on dapagliflozin plus metformin, and 18% for those on saxagliptin and metformin.

Patients on all three drugs also showed weight loss and blood pressure reductions roughly similar to the higher rates seen in the two control arms. The triple regimen was also well tolerated, with one patient having a minor hypoglycemic episode.

The empagliflozin and linagliptin study was sponsored by Boehringer Ingelheim, which markets both drugs. The dapagliflozin plus saxagliptin study was sponsored by Bristol-Myers Squibb and AstraZeneca, which market both drugs. Dr. DeFronzo is an adviser to and speaker for Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, and other drug companies. Dr. Rosenstock is a consultant to Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, and other drug companies.

[email protected]

On Twitter @mitchelzoler