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European Association for the Study of Diabetes (EASD): Annual Meeting
Diabetes driving ‘mishaps’ halved by web-based intervention
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.
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.
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.
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.
AT EASD 2014
Key clinical point: Type 1 diabetes patients identified as high-risk drivers had 2.5-fold more driving mishaps than those who were deemed low-risk drivers.
Major finding: There were 53% fewer driving mishaps experienced by high-risk diabetic drivers who underwent the additional web-based intervention versus those who had only routine care.
Data source: Randomized trial of 1,739 individuals with type 1 diabetes who registered with DiabetesDriving.com.
Disclosures: The study was funded by the National Institutes of Health. Lifescan, Abbot, and Dex4 provided supplies. Dr. Cox and coinvestigators had no conflicts of interest.
VIDEO: Insulin still mainstay of T2DM treatment
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.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT EASD 2014
Triple-drug success foreshadows T2DM combo pill
VIENNA – Adding agents from two relatively new oral hypoglycemic drug classes to metformin produced a rapid, incremental reduction in hemoglobin A1c 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 HbA1c 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 HbA1c 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 HbA1c level of 8%-12% while on stable metformin treatment. They averaged 53 years of age and had an average HbA1c 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 HbA1c 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 HbA1c 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.
Reducing tablet counts for patients is a way to move forward in managing type 2 diabetes. We already have formulations that combine two oral hypoglycemic drugs, and developing a single pill that combines three drugs seems like a logical next step. But the logistics of this are not simple. I have concerns about drug tolerability, and we need a much better understanding of the potential complementary effects of simultaneous treatment with metformin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, and a dipeptidyl peptidase-4 (DPP-4) inhibitor. In addition, in some patients, moving from treatment with a single drug to treatment with three drugs may be too great a leap. Sequential progression from one to two and then a third drug if still needed may be best for some patients.
 |
Dr. Melanie Davies |
Combination of metformin, an SGLT2 inhibitor, and a DPP-4 inhibitor has been suggested by many diabetologists as an attractive option, and I agree it has promise. These drugs are reasonably well tolerated and have good effects on hemoglobin A1c as well as blood pressure and weight loss, with a low risk of causing hypoglycemia.
Dr. Melanie J. Davies is professor of diabetes medicine at the University of Leicester, England. She has been a consultant to and speaker for Boehringer Ingelheim and several other drug companies. She made these comments in an interview.
Reducing tablet counts for patients is a way to move forward in managing type 2 diabetes. We already have formulations that combine two oral hypoglycemic drugs, and developing a single pill that combines three drugs seems like a logical next step. But the logistics of this are not simple. I have concerns about drug tolerability, and we need a much better understanding of the potential complementary effects of simultaneous treatment with metformin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, and a dipeptidyl peptidase-4 (DPP-4) inhibitor. In addition, in some patients, moving from treatment with a single drug to treatment with three drugs may be too great a leap. Sequential progression from one to two and then a third drug if still needed may be best for some patients.
|
Dr. Melanie Davies |
Combination of metformin, an SGLT2 inhibitor, and a DPP-4 inhibitor has been suggested by many diabetologists as an attractive option, and I agree it has promise. These drugs are reasonably well tolerated and have good effects on hemoglobin A1c as well as blood pressure and weight loss, with a low risk of causing hypoglycemia.
Dr. Melanie J. Davies is professor of diabetes medicine at the University of Leicester, England. She has been a consultant to and speaker for Boehringer Ingelheim and several other drug companies. She made these comments in an interview.
Reducing tablet counts for patients is a way to move forward in managing type 2 diabetes. We already have formulations that combine two oral hypoglycemic drugs, and developing a single pill that combines three drugs seems like a logical next step. But the logistics of this are not simple. I have concerns about drug tolerability, and we need a much better understanding of the potential complementary effects of simultaneous treatment with metformin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, and a dipeptidyl peptidase-4 (DPP-4) inhibitor. In addition, in some patients, moving from treatment with a single drug to treatment with three drugs may be too great a leap. Sequential progression from one to two and then a third drug if still needed may be best for some patients.
|
Dr. Melanie Davies |
Combination of metformin, an SGLT2 inhibitor, and a DPP-4 inhibitor has been suggested by many diabetologists as an attractive option, and I agree it has promise. These drugs are reasonably well tolerated and have good effects on hemoglobin A1c as well as blood pressure and weight loss, with a low risk of causing hypoglycemia.
Dr. Melanie J. Davies is professor of diabetes medicine at the University of Leicester, England. She has been a consultant to and speaker for Boehringer Ingelheim and several other drug companies. She made these comments in an interview.
VIENNA – Adding agents from two relatively new oral hypoglycemic drug classes to metformin produced a rapid, incremental reduction in hemoglobin A1c 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 HbA1c 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 HbA1c 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 HbA1c level of 8%-12% while on stable metformin treatment. They averaged 53 years of age and had an average HbA1c 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 HbA1c 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 HbA1c 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.
VIENNA – Adding agents from two relatively new oral hypoglycemic drug classes to metformin produced a rapid, incremental reduction in hemoglobin A1c 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 HbA1c 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 HbA1c 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 HbA1c level of 8%-12% while on stable metformin treatment. They averaged 53 years of age and had an average HbA1c 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 HbA1c 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 HbA1c 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.
AT EASD 2014
Key clinical point: Augmenting a metformin regimen with a combination of a SGLT2 inhibitor drug and a DPP-4 inhibitor produced greater glycemic control than adding one of these drugs alone in patients with type 2 diabetes.
Major finding: Treatment with 25 mg empagliflozin, linagliptin, and metformin produced an average 1.19% reduction in HbA1c after 24 weeks. Treatment with dapagliflozin, saxagliptin, and metformin produced an average 1.5% reduction in HbA1c after 24 weeks.
Data source: Two separate randomized controlled studies that enrolled 677 and 534 patients, respectively, with type 2 diabetes.
Disclosures: 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.
Complications rise for young people who miss glycemic goals
VIENNA – Young people worldwide who have type 1 diabetes are not achieving their glycemic targets and, as a result, experience suboptimal outcomes.
About 70% of children and teens and 81% of young adults did not meet their hemoglobin A1c targets, in a large records review. As a result, many are experiencing significantly more complications from poorly controlled diabetes, Dr. Lori Laffel and her colleagues reported at the annual meeting of the European Association for the Study of Diabetes.
“These results highlight the need for further improvements in the management of glycemic control ... in young people with type 1 diabetes, particularly for patents aged 19-25 years,” wrote Dr. Laffel, chief of the pediatric, adolescent, and young adult section at the Joslin Diabetes Center, Boston.
The study comprised the European participants (2,943) in the TEENs study, a worldwide, observational study of 5,960 young patients with type 1 diabetes (aged 8-25 years) who were treated at 219 centers in 20 countries. The target HbA1c levels varied by age: 7.5% for patients 18 years and younger, and 7% for those 19 years and older. Younger patients were divided into two groups (8-12 and 13-18 years old), while the third group comprised those aged 19-25 years.
The overall mean HbA1c in was 8.5%, with 35% of the entire group meeting their goals. Control rates did not vary much among the younger patients (39% in those aged 8-12 years and 37% in those aged 12-18 years). A smaller percentage of the older patients stayed on target (23%).
Associated complications were significantly more common in uncontrolled patients: In the 6 months before data were collected, about 6% of both younger groups and 7% of the older group had experienced diabetic ketoacidosis. In contrast, the incidence among well-controlled patients in all three groups was about 3%.
The oldest uncontrolled patients also had the highest incidence of severe hypoglycemia resulting in loss of consciousness or seizure – 6% compared to 36% of well-controlled patients that age.
Among the youngest uncontrolled patients, the incidence was less than 3% in each group. Severe hypoglycemia incidence was similar in the middle group, at about 2% in the uncontrolled vs. 3% in the controlled patients.
The incidence of microalbuminuria soared among the oldest uncontrolled patients, reaching almost 9%, compared with just under 6% of controlled patients. For the youngest patients, the rates were similar (about 1% of each group). It was doubled in the middle group, at 5% in uncontrolled vs. 2.4% of controlled patients.
Neuropathy occurred in 10% of the oldest uncontrolled patients vs. 8% of well controlled. For the youngest, the rates doubled (3% vs. 1.5%, respectively). They more than doubled in the middle group (almost 6% vs. 2%).
The rates of retinopathy needing treatment were also elevated in the oldest uncontrolled patients, compared with the controlled patients (4% vs. 1.5%). However, in both younger groups, they were well under 1% regardless of control.
A multivariate analysis determined that diabetic ketoacidosis and diabetic neuropathy were significantly associated with uncontrolled HbA1c (odds ratio, 0.53 and 0.47, respectively).
Dr Laffel has received research support from Sanofi-Aventis, which funded the study, as well as other pharmaceutical companies. Two coauthors were Sanofi employees.
On Twitter @alz_gal
VIENNA – Young people worldwide who have type 1 diabetes are not achieving their glycemic targets and, as a result, experience suboptimal outcomes.
About 70% of children and teens and 81% of young adults did not meet their hemoglobin A1c targets, in a large records review. As a result, many are experiencing significantly more complications from poorly controlled diabetes, Dr. Lori Laffel and her colleagues reported at the annual meeting of the European Association for the Study of Diabetes.
“These results highlight the need for further improvements in the management of glycemic control ... in young people with type 1 diabetes, particularly for patents aged 19-25 years,” wrote Dr. Laffel, chief of the pediatric, adolescent, and young adult section at the Joslin Diabetes Center, Boston.
The study comprised the European participants (2,943) in the TEENs study, a worldwide, observational study of 5,960 young patients with type 1 diabetes (aged 8-25 years) who were treated at 219 centers in 20 countries. The target HbA1c levels varied by age: 7.5% for patients 18 years and younger, and 7% for those 19 years and older. Younger patients were divided into two groups (8-12 and 13-18 years old), while the third group comprised those aged 19-25 years.
The overall mean HbA1c in was 8.5%, with 35% of the entire group meeting their goals. Control rates did not vary much among the younger patients (39% in those aged 8-12 years and 37% in those aged 12-18 years). A smaller percentage of the older patients stayed on target (23%).
Associated complications were significantly more common in uncontrolled patients: In the 6 months before data were collected, about 6% of both younger groups and 7% of the older group had experienced diabetic ketoacidosis. In contrast, the incidence among well-controlled patients in all three groups was about 3%.
The oldest uncontrolled patients also had the highest incidence of severe hypoglycemia resulting in loss of consciousness or seizure – 6% compared to 36% of well-controlled patients that age.
Among the youngest uncontrolled patients, the incidence was less than 3% in each group. Severe hypoglycemia incidence was similar in the middle group, at about 2% in the uncontrolled vs. 3% in the controlled patients.
The incidence of microalbuminuria soared among the oldest uncontrolled patients, reaching almost 9%, compared with just under 6% of controlled patients. For the youngest patients, the rates were similar (about 1% of each group). It was doubled in the middle group, at 5% in uncontrolled vs. 2.4% of controlled patients.
Neuropathy occurred in 10% of the oldest uncontrolled patients vs. 8% of well controlled. For the youngest, the rates doubled (3% vs. 1.5%, respectively). They more than doubled in the middle group (almost 6% vs. 2%).
The rates of retinopathy needing treatment were also elevated in the oldest uncontrolled patients, compared with the controlled patients (4% vs. 1.5%). However, in both younger groups, they were well under 1% regardless of control.
A multivariate analysis determined that diabetic ketoacidosis and diabetic neuropathy were significantly associated with uncontrolled HbA1c (odds ratio, 0.53 and 0.47, respectively).
Dr Laffel has received research support from Sanofi-Aventis, which funded the study, as well as other pharmaceutical companies. Two coauthors were Sanofi employees.
On Twitter @alz_gal
VIENNA – Young people worldwide who have type 1 diabetes are not achieving their glycemic targets and, as a result, experience suboptimal outcomes.
About 70% of children and teens and 81% of young adults did not meet their hemoglobin A1c targets, in a large records review. As a result, many are experiencing significantly more complications from poorly controlled diabetes, Dr. Lori Laffel and her colleagues reported at the annual meeting of the European Association for the Study of Diabetes.
“These results highlight the need for further improvements in the management of glycemic control ... in young people with type 1 diabetes, particularly for patents aged 19-25 years,” wrote Dr. Laffel, chief of the pediatric, adolescent, and young adult section at the Joslin Diabetes Center, Boston.
The study comprised the European participants (2,943) in the TEENs study, a worldwide, observational study of 5,960 young patients with type 1 diabetes (aged 8-25 years) who were treated at 219 centers in 20 countries. The target HbA1c levels varied by age: 7.5% for patients 18 years and younger, and 7% for those 19 years and older. Younger patients were divided into two groups (8-12 and 13-18 years old), while the third group comprised those aged 19-25 years.
The overall mean HbA1c in was 8.5%, with 35% of the entire group meeting their goals. Control rates did not vary much among the younger patients (39% in those aged 8-12 years and 37% in those aged 12-18 years). A smaller percentage of the older patients stayed on target (23%).
Associated complications were significantly more common in uncontrolled patients: In the 6 months before data were collected, about 6% of both younger groups and 7% of the older group had experienced diabetic ketoacidosis. In contrast, the incidence among well-controlled patients in all three groups was about 3%.
The oldest uncontrolled patients also had the highest incidence of severe hypoglycemia resulting in loss of consciousness or seizure – 6% compared to 36% of well-controlled patients that age.
Among the youngest uncontrolled patients, the incidence was less than 3% in each group. Severe hypoglycemia incidence was similar in the middle group, at about 2% in the uncontrolled vs. 3% in the controlled patients.
The incidence of microalbuminuria soared among the oldest uncontrolled patients, reaching almost 9%, compared with just under 6% of controlled patients. For the youngest patients, the rates were similar (about 1% of each group). It was doubled in the middle group, at 5% in uncontrolled vs. 2.4% of controlled patients.
Neuropathy occurred in 10% of the oldest uncontrolled patients vs. 8% of well controlled. For the youngest, the rates doubled (3% vs. 1.5%, respectively). They more than doubled in the middle group (almost 6% vs. 2%).
The rates of retinopathy needing treatment were also elevated in the oldest uncontrolled patients, compared with the controlled patients (4% vs. 1.5%). However, in both younger groups, they were well under 1% regardless of control.
A multivariate analysis determined that diabetic ketoacidosis and diabetic neuropathy were significantly associated with uncontrolled HbA1c (odds ratio, 0.53 and 0.47, respectively).
Dr Laffel has received research support from Sanofi-Aventis, which funded the study, as well as other pharmaceutical companies. Two coauthors were Sanofi employees.
On Twitter @alz_gal
AT EASD 2014
Key clinical point: About three-fourths of children and young people with type 1 diabetes did not meet their hemoglobin A1c goals.
Major finding: Complications for those with uncontrolled diabetes were especially frequent in patients aged 19-25 years, with 10% developing neuropathy and 9% microalbuminuria.
Data source: TEENs, a records review comprising 5,960 type 1 diabetes patients aged 8-25 years.
Disclosures: Dr Laffel has received research support from Sanofi-Aventis, which funded the study, as well as other pharmaceutical companies. Two coauthors were Sanofi employees.