EASD 2012

BERLIN – In patients with type 1 diabetes and end-stage renal disease, a combined pancreas/kidney transplant was associated with significantly better 15-year survival than a single kidney graft alone.

Patients who got the simultaneous transplant were 30% more likely to survive to 15 years than were those who received a living donor kidney. Those patients who got a single kidney from a deceased donor, however, were 30% less likely to survive for 15 years after the operation, Dr. Trond Jenssen said at the annual meeting of the European Association for the Study of Diabetes.

The combined graft is the preferred method of treating end-stage renal disease (ESRD) caused by diabetic nephropathy, said Dr. Jenssen of Oslo University. Not all patients are suited for it, however.

"According to the algorithm at our center, if you are older than 55 or too sick, you have to decide between the living and deceased donor single kidney graft. Patients who are younger and have less comorbidity are the ones considered for a combined transplant," he explained.

Since those who have the dual-organ operation almost always normalize their glycemic values afterward, Dr. Jenssen said, it’s assumed that they will live longer than those who get only a kidney, but studies are divided on the finding.

"The literature over the past 10 years has differed," he said. Comparing studies among institutions is impossible because of the differences in surgical technique and immunosuppressive regimens; the patient populations can also vary widely.

Oslo University is in a unique place to study the issue, Dr. Jenssen suggested. The facility is the national transplant center, with nearly 30 years of full follow-up data on 630 type 1 diabetes patients who were transplanted for ESRD. All of the patients are followed at least annually and their information is entered into the Norwegian Renal Registry.

"Because patients in Norway tend to be very faithful to their doctors, we have not lost a single one of these to follow-up," he said.

Of the entire group, 222 received the simultaneous transplants, 171 received a living donor single kidney, and 237 got a deceased donor kidney. Patients who received the simultaneous transplant were younger than the living or deceased single graft groups (41 years vs. 45 and 55 years, respectively).

The study controlled for the evolution of surgical techniques and immunosuppressant regimens. Before 1989, all pancreases were transplanted with occluded ducts. From 1989 to 1999, the exocrine duct drained into the bladder, and since 2000, into the intestine. The pancreas has always been connected to the systemic circulation by the iliac artery and vein.

Before 2000, the immunosuppressive regiment consisted of cyclosporine and azathioprine; afterwards, tacrolimus and mycophenolate. All patients from both eras take a daily dose of prednisone as well.

There was no induction therapy before 2000, Dr. Jenssen said. After that time, patients receiving a single kidney began to receive basiliximab and the dual-transplant patients got thymoglobulin.

The overall 15-year survival rate was 50% in the simultaneous-graft group, 30% in the living donor kidney group, and 12% in the deceased donor kidney group.

Dr. Jenssen presented two regression models. In the first one, which controlled for recipient age, time on dialysis, and the transplant era, patients who got the dual graft were significantly more likely to survive to 15 years than were those who got the single live donor kidney (hazard ratio, 0.70). Patients who received a single deceased donor kidney were 31% less likely to survive (HR, 1.29).

These differences were no longer significant in a second model, which also controlled for donor age, but Dr. Jenssen said that the difference was not clinically meaningful.

Among the 317 patients who died during the study, the most common cause was cardiovascular disease (59%). Infections claimed 15% and malignancy 8%. The remainder of the patients died from causes that he did not specify.

Dr. Jenssen said that he did not control for glycemic index because the hemoglobin A_1c test was unavailable during a large part of the follow-up period. He intends to work that into the model eventually, he added.

Dr. Jenssen had no financial disclosures.

BERLIN – In patients with type 1 diabetes and end-stage renal disease, a combined pancreas/kidney transplant was associated with significantly better 15-year survival than a single kidney graft alone.

Patients who got the simultaneous transplant were 30% more likely to survive to 15 years than were those who received a living donor kidney. Those patients who got a single kidney from a deceased donor, however, were 30% less likely to survive for 15 years after the operation, Dr. Trond Jenssen said at the annual meeting of the European Association for the Study of Diabetes.

The combined graft is the preferred method of treating end-stage renal disease (ESRD) caused by diabetic nephropathy, said Dr. Jenssen of Oslo University. Not all patients are suited for it, however.

"According to the algorithm at our center, if you are older than 55 or too sick, you have to decide between the living and deceased donor single kidney graft. Patients who are younger and have less comorbidity are the ones considered for a combined transplant," he explained.

Since those who have the dual-organ operation almost always normalize their glycemic values afterward, Dr. Jenssen said, it’s assumed that they will live longer than those who get only a kidney, but studies are divided on the finding.

"The literature over the past 10 years has differed," he said. Comparing studies among institutions is impossible because of the differences in surgical technique and immunosuppressive regimens; the patient populations can also vary widely.

Oslo University is in a unique place to study the issue, Dr. Jenssen suggested. The facility is the national transplant center, with nearly 30 years of full follow-up data on 630 type 1 diabetes patients who were transplanted for ESRD. All of the patients are followed at least annually and their information is entered into the Norwegian Renal Registry.

"Because patients in Norway tend to be very faithful to their doctors, we have not lost a single one of these to follow-up," he said.

Of the entire group, 222 received the simultaneous transplants, 171 received a living donor single kidney, and 237 got a deceased donor kidney. Patients who received the simultaneous transplant were younger than the living or deceased single graft groups (41 years vs. 45 and 55 years, respectively).

The study controlled for the evolution of surgical techniques and immunosuppressant regimens. Before 1989, all pancreases were transplanted with occluded ducts. From 1989 to 1999, the exocrine duct drained into the bladder, and since 2000, into the intestine. The pancreas has always been connected to the systemic circulation by the iliac artery and vein.

Before 2000, the immunosuppressive regiment consisted of cyclosporine and azathioprine; afterwards, tacrolimus and mycophenolate. All patients from both eras take a daily dose of prednisone as well.

There was no induction therapy before 2000, Dr. Jenssen said. After that time, patients receiving a single kidney began to receive basiliximab and the dual-transplant patients got thymoglobulin.

The overall 15-year survival rate was 50% in the simultaneous-graft group, 30% in the living donor kidney group, and 12% in the deceased donor kidney group.

Dr. Jenssen presented two regression models. In the first one, which controlled for recipient age, time on dialysis, and the transplant era, patients who got the dual graft were significantly more likely to survive to 15 years than were those who got the single live donor kidney (hazard ratio, 0.70). Patients who received a single deceased donor kidney were 31% less likely to survive (HR, 1.29).

These differences were no longer significant in a second model, which also controlled for donor age, but Dr. Jenssen said that the difference was not clinically meaningful.

Among the 317 patients who died during the study, the most common cause was cardiovascular disease (59%). Infections claimed 15% and malignancy 8%. The remainder of the patients died from causes that he did not specify.

Dr. Jenssen said that he did not control for glycemic index because the hemoglobin A_1c test was unavailable during a large part of the follow-up period. He intends to work that into the model eventually, he added.

Dr. Jenssen had no financial disclosures.

BERLIN – In patients with type 1 diabetes and end-stage renal disease, a combined pancreas/kidney transplant was associated with significantly better 15-year survival than a single kidney graft alone.

Patients who got the simultaneous transplant were 30% more likely to survive to 15 years than were those who received a living donor kidney. Those patients who got a single kidney from a deceased donor, however, were 30% less likely to survive for 15 years after the operation, Dr. Trond Jenssen said at the annual meeting of the European Association for the Study of Diabetes.

The combined graft is the preferred method of treating end-stage renal disease (ESRD) caused by diabetic nephropathy, said Dr. Jenssen of Oslo University. Not all patients are suited for it, however.

"According to the algorithm at our center, if you are older than 55 or too sick, you have to decide between the living and deceased donor single kidney graft. Patients who are younger and have less comorbidity are the ones considered for a combined transplant," he explained.

Since those who have the dual-organ operation almost always normalize their glycemic values afterward, Dr. Jenssen said, it’s assumed that they will live longer than those who get only a kidney, but studies are divided on the finding.

"The literature over the past 10 years has differed," he said. Comparing studies among institutions is impossible because of the differences in surgical technique and immunosuppressive regimens; the patient populations can also vary widely.

Oslo University is in a unique place to study the issue, Dr. Jenssen suggested. The facility is the national transplant center, with nearly 30 years of full follow-up data on 630 type 1 diabetes patients who were transplanted for ESRD. All of the patients are followed at least annually and their information is entered into the Norwegian Renal Registry.

"Because patients in Norway tend to be very faithful to their doctors, we have not lost a single one of these to follow-up," he said.

Of the entire group, 222 received the simultaneous transplants, 171 received a living donor single kidney, and 237 got a deceased donor kidney. Patients who received the simultaneous transplant were younger than the living or deceased single graft groups (41 years vs. 45 and 55 years, respectively).

The study controlled for the evolution of surgical techniques and immunosuppressant regimens. Before 1989, all pancreases were transplanted with occluded ducts. From 1989 to 1999, the exocrine duct drained into the bladder, and since 2000, into the intestine. The pancreas has always been connected to the systemic circulation by the iliac artery and vein.

Before 2000, the immunosuppressive regiment consisted of cyclosporine and azathioprine; afterwards, tacrolimus and mycophenolate. All patients from both eras take a daily dose of prednisone as well.

There was no induction therapy before 2000, Dr. Jenssen said. After that time, patients receiving a single kidney began to receive basiliximab and the dual-transplant patients got thymoglobulin.

The overall 15-year survival rate was 50% in the simultaneous-graft group, 30% in the living donor kidney group, and 12% in the deceased donor kidney group.

Dr. Jenssen presented two regression models. In the first one, which controlled for recipient age, time on dialysis, and the transplant era, patients who got the dual graft were significantly more likely to survive to 15 years than were those who got the single live donor kidney (hazard ratio, 0.70). Patients who received a single deceased donor kidney were 31% less likely to survive (HR, 1.29).

These differences were no longer significant in a second model, which also controlled for donor age, but Dr. Jenssen said that the difference was not clinically meaningful.

Among the 317 patients who died during the study, the most common cause was cardiovascular disease (59%). Infections claimed 15% and malignancy 8%. The remainder of the patients died from causes that he did not specify.

Dr. Jenssen said that he did not control for glycemic index because the hemoglobin A_1c test was unavailable during a large part of the follow-up period. He intends to work that into the model eventually, he added.

Dr. Jenssen had no financial disclosures.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age. The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%. All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed. After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study. At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline. More than half of the subjects (62%) reached a level of 7%. Fasting glucose and acute glucose response improved significantly. Insulin sensitivity improved early and that was maintained. Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age. The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%. All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed. After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study. At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline. More than half of the subjects (62%) reached a level of 7%. Fasting glucose and acute glucose response improved significantly. Insulin sensitivity improved early and that was maintained. Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age. The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%. All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed. After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study. At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline. More than half of the subjects (62%) reached a level of 7%. Fasting glucose and acute glucose response improved significantly. Insulin sensitivity improved early and that was maintained. Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

Medicine has been awash over the past decade or so in new types of drugs to treat type 2 diabetes, but the impact of this abundance on improving patient care remains uncertain. Perhaps because of this, or despite it, the number of new antihyperglycemic drugs continues to grow.

At the annual meeting of the European Association for the Study of Diabetes (EASD) in Berlin in early October, during different sessions and with no signs of coordination, two speakers put the same image up on the screen during their talks. Both images graphically depicted and contrasted the pace of drug introductions for diabetes and for hypertension over the past 60 years or so.

Jina Lee/Wikimedia Commons

For antihypertensives, the pace was steady and linear: Ten drug classes came out during the years from 1950 to now at a steady clip of one or two each decade.

In contrast, drugs aimed at reducing blood sugar or boosting insulin release or sensitivity languished for a long time, with only two drug classes available until the 1990s, insulin and the sulfonylureas. But starting with the introduction of metformin, the first Food and Drug Administration–approved biguanide, at the end of 1994, the FDA approved drugs from eight additional drug classes, a rate of a new drug type every 2 years.

Why such a striking difference, especially during the past 10 years when commercial interest in new drug development for blood pressure–lowering drugs has dwindled to virtual indifference? I asked one of the speakers who made the comparison during the meeting, Yale diabetologist Silvio Inzucchi.

"The drugs now available to treat hypertension are reasonably good, so why waste money developing new agents when most patients are successfully treated with what we have?" he queried. However, "in diabetes we still have significant side effects, and no diabetes drug – except perhaps insulin – is universally effective. So there remains room for better, more effective, and safer medications. I am still waiting for the perfect diabetes drug."

It might come as news to physicians who treat hypertension that they have "perfect" drugs to prescribe, but the antihypertensive big three of diuretics, beta-blockers, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers have pretty much become the mainstays of blood pressure reduction. For diabetes, the situation is not nearly so clear.

Last June, the EASD and the American Diabetes Association released recommendations on managing type 2 diabetes (a panel cochaired by Dr. Inzucchi). The groups named metformin as their initial go-to drug, and highlighted five other drug classes as the top choices for a second or third drug to add for patients who need more than metformin. Those five other drug classes are sulfonylureas (like glipizide), thiazolidinediones (like pioglitazone), DPP-4 inhibitors (like sitagliptin), GLP-1 receptor agonists (like exenatide), and insulin.

That means the top tier of recommended drugs includes only three of the agents that have come on the scene in the recent rush of the past 17 years – the thiazolidinediones, the DPP-4 inhibitors, and the GLP-1 receptor agonists. The recommendation panel decided that five other recently-approved drug classes did not really add much to the treatment mix.

As Dr. Inzucchi told me:

"The drugs we left off the main figure are suboptimal for a variety of reasons. Some are minimally effective, some very expensive, some have intolerable side effects, and some are too hard to take.

"There is still room for more agents, but they have to be safer, better tolerated, and preferably more durable in their effectiveness than what we currently have," he said.

Other reports at the EASD meeting showed that the wave of new drug types for treating diabetes will not ebb soon. Agents awaiting regulatory action or in clinical studies include SGLT2 inhibitors, dual PPAR-receptor agonists, SIRT1 activators, and glucagon-receptor antagonists.

The number of alternatives for treating diabetes is no longer the issue. The question is, how many of the different drug types really help patients?

–Mitchel Zoler (on Twitter @mitchelzoler)

Medicine has been awash over the past decade or so in new types of drugs to treat type 2 diabetes, but the impact of this abundance on improving patient care remains uncertain. Perhaps because of this, or despite it, the number of new antihyperglycemic drugs continues to grow.

At the annual meeting of the European Association for the Study of Diabetes (EASD) in Berlin in early October, during different sessions and with no signs of coordination, two speakers put the same image up on the screen during their talks. Both images graphically depicted and contrasted the pace of drug introductions for diabetes and for hypertension over the past 60 years or so.

Jina Lee/Wikimedia Commons

For antihypertensives, the pace was steady and linear: Ten drug classes came out during the years from 1950 to now at a steady clip of one or two each decade.

In contrast, drugs aimed at reducing blood sugar or boosting insulin release or sensitivity languished for a long time, with only two drug classes available until the 1990s, insulin and the sulfonylureas. But starting with the introduction of metformin, the first Food and Drug Administration–approved biguanide, at the end of 1994, the FDA approved drugs from eight additional drug classes, a rate of a new drug type every 2 years.

Why such a striking difference, especially during the past 10 years when commercial interest in new drug development for blood pressure–lowering drugs has dwindled to virtual indifference? I asked one of the speakers who made the comparison during the meeting, Yale diabetologist Silvio Inzucchi.

"The drugs now available to treat hypertension are reasonably good, so why waste money developing new agents when most patients are successfully treated with what we have?" he queried. However, "in diabetes we still have significant side effects, and no diabetes drug – except perhaps insulin – is universally effective. So there remains room for better, more effective, and safer medications. I am still waiting for the perfect diabetes drug."

It might come as news to physicians who treat hypertension that they have "perfect" drugs to prescribe, but the antihypertensive big three of diuretics, beta-blockers, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers have pretty much become the mainstays of blood pressure reduction. For diabetes, the situation is not nearly so clear.

Last June, the EASD and the American Diabetes Association released recommendations on managing type 2 diabetes (a panel cochaired by Dr. Inzucchi). The groups named metformin as their initial go-to drug, and highlighted five other drug classes as the top choices for a second or third drug to add for patients who need more than metformin. Those five other drug classes are sulfonylureas (like glipizide), thiazolidinediones (like pioglitazone), DPP-4 inhibitors (like sitagliptin), GLP-1 receptor agonists (like exenatide), and insulin.

That means the top tier of recommended drugs includes only three of the agents that have come on the scene in the recent rush of the past 17 years – the thiazolidinediones, the DPP-4 inhibitors, and the GLP-1 receptor agonists. The recommendation panel decided that five other recently-approved drug classes did not really add much to the treatment mix.

As Dr. Inzucchi told me:

"The drugs we left off the main figure are suboptimal for a variety of reasons. Some are minimally effective, some very expensive, some have intolerable side effects, and some are too hard to take.

"There is still room for more agents, but they have to be safer, better tolerated, and preferably more durable in their effectiveness than what we currently have," he said.

Other reports at the EASD meeting showed that the wave of new drug types for treating diabetes will not ebb soon. Agents awaiting regulatory action or in clinical studies include SGLT2 inhibitors, dual PPAR-receptor agonists, SIRT1 activators, and glucagon-receptor antagonists.

The number of alternatives for treating diabetes is no longer the issue. The question is, how many of the different drug types really help patients?

–Mitchel Zoler (on Twitter @mitchelzoler)

Medicine has been awash over the past decade or so in new types of drugs to treat type 2 diabetes, but the impact of this abundance on improving patient care remains uncertain. Perhaps because of this, or despite it, the number of new antihyperglycemic drugs continues to grow.

At the annual meeting of the European Association for the Study of Diabetes (EASD) in Berlin in early October, during different sessions and with no signs of coordination, two speakers put the same image up on the screen during their talks. Both images graphically depicted and contrasted the pace of drug introductions for diabetes and for hypertension over the past 60 years or so.

Jina Lee/Wikimedia Commons

For antihypertensives, the pace was steady and linear: Ten drug classes came out during the years from 1950 to now at a steady clip of one or two each decade.

In contrast, drugs aimed at reducing blood sugar or boosting insulin release or sensitivity languished for a long time, with only two drug classes available until the 1990s, insulin and the sulfonylureas. But starting with the introduction of metformin, the first Food and Drug Administration–approved biguanide, at the end of 1994, the FDA approved drugs from eight additional drug classes, a rate of a new drug type every 2 years.

Why such a striking difference, especially during the past 10 years when commercial interest in new drug development for blood pressure–lowering drugs has dwindled to virtual indifference? I asked one of the speakers who made the comparison during the meeting, Yale diabetologist Silvio Inzucchi.

"The drugs now available to treat hypertension are reasonably good, so why waste money developing new agents when most patients are successfully treated with what we have?" he queried. However, "in diabetes we still have significant side effects, and no diabetes drug – except perhaps insulin – is universally effective. So there remains room for better, more effective, and safer medications. I am still waiting for the perfect diabetes drug."

It might come as news to physicians who treat hypertension that they have "perfect" drugs to prescribe, but the antihypertensive big three of diuretics, beta-blockers, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers have pretty much become the mainstays of blood pressure reduction. For diabetes, the situation is not nearly so clear.

Last June, the EASD and the American Diabetes Association released recommendations on managing type 2 diabetes (a panel cochaired by Dr. Inzucchi). The groups named metformin as their initial go-to drug, and highlighted five other drug classes as the top choices for a second or third drug to add for patients who need more than metformin. Those five other drug classes are sulfonylureas (like glipizide), thiazolidinediones (like pioglitazone), DPP-4 inhibitors (like sitagliptin), GLP-1 receptor agonists (like exenatide), and insulin.

That means the top tier of recommended drugs includes only three of the agents that have come on the scene in the recent rush of the past 17 years – the thiazolidinediones, the DPP-4 inhibitors, and the GLP-1 receptor agonists. The recommendation panel decided that five other recently-approved drug classes did not really add much to the treatment mix.

As Dr. Inzucchi told me:

"The drugs we left off the main figure are suboptimal for a variety of reasons. Some are minimally effective, some very expensive, some have intolerable side effects, and some are too hard to take.

"There is still room for more agents, but they have to be safer, better tolerated, and preferably more durable in their effectiveness than what we currently have," he said.

Other reports at the EASD meeting showed that the wave of new drug types for treating diabetes will not ebb soon. Agents awaiting regulatory action or in clinical studies include SGLT2 inhibitors, dual PPAR-receptor agonists, SIRT1 activators, and glucagon-receptor antagonists.

The number of alternatives for treating diabetes is no longer the issue. The question is, how many of the different drug types really help patients?

–Mitchel Zoler (on Twitter @mitchelzoler)

BERLIN – Treatment of type 2 diabetes patients with canagliflozin, an investigational drug that boosts urinary glucose excretion, produced a clear rise in glycemic control while also dropping blood pressure and weight, compared with the established agent sitagliptin, in a phase III study with 755 patients.

"This is a very nice tool to reduce hemoglobin A_1c, blood pressure, and weight all together with relatively nice results," Dr. Guntram Schernthaner said at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

The major apparent downside of canagliflozin, an inhibitor of the sodium glucose cotransporter 2 (SGLT2), was its association with a 15% rate of genital mycotic infections in women and a 9% rate in men, compared with rates of 4% in women and less than 1% in men in the comparator arm.

The benefits from canagliflozin were "impressive. It looks real," commented Dr. Bernard Zinman, director of the Center for Diabetes at Mount Sinai Hospital in Toronto.

It’s currently unclear whether the significant blood pressure and weight loss effects of the drug plus its antihyperglycemic effect will cut cardiovascular events. That’s under study, he noted, and will be a key to whether canagliflozin and other drugs in its class become major players for treating patients with diabetes. Dr. Zinman also wondered how the genital infection problem will play out for these drugs. "That will be an issue. Physicians may stay away from using it on women if one in six gets an infection," he said in an interview.

The phase III comparison between canagliflozin and sitagliptin reported by Dr. Schernthaner was one of several reports on phase III studies released during the past few months by Janssen, the company developing canagliflozin. Last May, Janssen submitted a marketing approval application to the Food and Drug Administration for the drug.

Canagliflozin is one of several SGLT2 inhibitors now under development for diabetes. They boost the amount of glucose entering urine, and also inhibit intestinal glucose absorption. Dapagliflozin, another drug from the class, also has FDA approval pending, while empagliflozin is now in several phase III studies.

Dr. Schernthaner’s findings came from 755 patients with type 2 diabetes who remained poorly controlled despite stable treatment with metformin and a sulfonylurea. Patients had an average age of 57 years, they had type 2 diabetes for an average of 10 years, their average hemoglobin A_1c was 8.1%, and their average fasting plasma glucose was 9.2 mmol/L. The researchers randomized 378 patients to receive 100 mg sitagliptin daily and 377 to received 300 mg canagliflozin daily.

After 52 weeks, hemoglobin A_1c fell an average 1.03% compared with baseline in the canagliflozin arm and 0.66% in the sitagliptin group, a statistically significant difference for the study’s primary end point, reported Dr. Schernthaner, a professor at Rudolfstiftung Hospital in Vienna.

Other statistically significant between-group differences included the drop in fasting plasma glucose, 1.7 mmol/L with canagliflozin and 0.3 mmol/L with sitagliptin, the change in body weight, an average 2.3 kg drop with canagliflozin and a 0.1 kg rise with sitagliptin, and blood pressure change, a fall of 5.3 mm Hg with canagliflozin and a +0.9/–0.3 change with sitagliptin.

Mitchel L. Zoler/IMNG Medical Media

Rates of adverse events, including serious adverse events leading to withdrawal from the study, and hypoglycemic episodes, were similar in the two treatment arms, with the only substantial difference being the excess genital mycotic infections with canagliflozin.

"The interesting question is how would an SGLT2 inhibitor act when given along with a dipeptidyl peptidase-4 inhibitor" like sitagliptin, commented Dr. Baptist J. Gallwitz, professor of diabetology and endocrinology at Tubingen University Hospital in Germany. "The SGLT-2 inhibitor drugs will be an important class because they have a distinct, independent mode of action. You can theoretically combine them with any other drug and use them at any stage of diabetes," he said in an interview.

One troubling feature of the new canagliflozin study was the high rate of patients who dropped out, 44% of those in the sitagliptin arm and 33% in the canagliflozin group. Many of the dropouts occurred when patients failed to meet prespecified glycemic targets – 23% of patients in the sitagliptin arm and 11% put on canagliflozin.

"You need to be cautious. The tremendous dropout rate is not acceptable," said Dr. Zinman. "It’s very difficult to interpret a study with that kind of dropout."

Another possible flaw in the study was using sitagliptin as the comparator on top of background treatment with another secretagogue, a sulfonylurea. It’s possible that "patients were already getting the maximum benefit from the sulfonylurea" and so couldn’t show much additional benefit from also receiving canagliflozin, Dr. Zinman said.

The study was sponsored by Janssen, the company developing canagliflozin. Dr. Schernthaner said that he has received honoraria and research funding from Janssen, AstraZeneca and Bristol-Myers Squibb, the companies developing dapagliflozin, and from Boehringer Ingelheim, the company developing empagliflozin. Dr. Zinman said that he has received honoraria and research funding from Johnson & Johnson (the parent company of Janssen), and Boehringer Ingelheim and other drug companies. Dr. Gallwitz said that he has received honoraria and research funding from Boehringer Ingelheim, AstraZeneca and Bristol-Myers Squibb, and other drug companies.

BERLIN – Treatment of type 2 diabetes patients with canagliflozin, an investigational drug that boosts urinary glucose excretion, produced a clear rise in glycemic control while also dropping blood pressure and weight, compared with the established agent sitagliptin, in a phase III study with 755 patients.

"This is a very nice tool to reduce hemoglobin A_1c, blood pressure, and weight all together with relatively nice results," Dr. Guntram Schernthaner said at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

The major apparent downside of canagliflozin, an inhibitor of the sodium glucose cotransporter 2 (SGLT2), was its association with a 15% rate of genital mycotic infections in women and a 9% rate in men, compared with rates of 4% in women and less than 1% in men in the comparator arm.

The benefits from canagliflozin were "impressive. It looks real," commented Dr. Bernard Zinman, director of the Center for Diabetes at Mount Sinai Hospital in Toronto.

It’s currently unclear whether the significant blood pressure and weight loss effects of the drug plus its antihyperglycemic effect will cut cardiovascular events. That’s under study, he noted, and will be a key to whether canagliflozin and other drugs in its class become major players for treating patients with diabetes. Dr. Zinman also wondered how the genital infection problem will play out for these drugs. "That will be an issue. Physicians may stay away from using it on women if one in six gets an infection," he said in an interview.

The phase III comparison between canagliflozin and sitagliptin reported by Dr. Schernthaner was one of several reports on phase III studies released during the past few months by Janssen, the company developing canagliflozin. Last May, Janssen submitted a marketing approval application to the Food and Drug Administration for the drug.

Canagliflozin is one of several SGLT2 inhibitors now under development for diabetes. They boost the amount of glucose entering urine, and also inhibit intestinal glucose absorption. Dapagliflozin, another drug from the class, also has FDA approval pending, while empagliflozin is now in several phase III studies.

Dr. Schernthaner’s findings came from 755 patients with type 2 diabetes who remained poorly controlled despite stable treatment with metformin and a sulfonylurea. Patients had an average age of 57 years, they had type 2 diabetes for an average of 10 years, their average hemoglobin A_1c was 8.1%, and their average fasting plasma glucose was 9.2 mmol/L. The researchers randomized 378 patients to receive 100 mg sitagliptin daily and 377 to received 300 mg canagliflozin daily.

After 52 weeks, hemoglobin A_1c fell an average 1.03% compared with baseline in the canagliflozin arm and 0.66% in the sitagliptin group, a statistically significant difference for the study’s primary end point, reported Dr. Schernthaner, a professor at Rudolfstiftung Hospital in Vienna.

Other statistically significant between-group differences included the drop in fasting plasma glucose, 1.7 mmol/L with canagliflozin and 0.3 mmol/L with sitagliptin, the change in body weight, an average 2.3 kg drop with canagliflozin and a 0.1 kg rise with sitagliptin, and blood pressure change, a fall of 5.3 mm Hg with canagliflozin and a +0.9/–0.3 change with sitagliptin.

Mitchel L. Zoler/IMNG Medical Media

Rates of adverse events, including serious adverse events leading to withdrawal from the study, and hypoglycemic episodes, were similar in the two treatment arms, with the only substantial difference being the excess genital mycotic infections with canagliflozin.

"The interesting question is how would an SGLT2 inhibitor act when given along with a dipeptidyl peptidase-4 inhibitor" like sitagliptin, commented Dr. Baptist J. Gallwitz, professor of diabetology and endocrinology at Tubingen University Hospital in Germany. "The SGLT-2 inhibitor drugs will be an important class because they have a distinct, independent mode of action. You can theoretically combine them with any other drug and use them at any stage of diabetes," he said in an interview.

One troubling feature of the new canagliflozin study was the high rate of patients who dropped out, 44% of those in the sitagliptin arm and 33% in the canagliflozin group. Many of the dropouts occurred when patients failed to meet prespecified glycemic targets – 23% of patients in the sitagliptin arm and 11% put on canagliflozin.

"You need to be cautious. The tremendous dropout rate is not acceptable," said Dr. Zinman. "It’s very difficult to interpret a study with that kind of dropout."

Another possible flaw in the study was using sitagliptin as the comparator on top of background treatment with another secretagogue, a sulfonylurea. It’s possible that "patients were already getting the maximum benefit from the sulfonylurea" and so couldn’t show much additional benefit from also receiving canagliflozin, Dr. Zinman said.

The study was sponsored by Janssen, the company developing canagliflozin. Dr. Schernthaner said that he has received honoraria and research funding from Janssen, AstraZeneca and Bristol-Myers Squibb, the companies developing dapagliflozin, and from Boehringer Ingelheim, the company developing empagliflozin. Dr. Zinman said that he has received honoraria and research funding from Johnson & Johnson (the parent company of Janssen), and Boehringer Ingelheim and other drug companies. Dr. Gallwitz said that he has received honoraria and research funding from Boehringer Ingelheim, AstraZeneca and Bristol-Myers Squibb, and other drug companies.

BERLIN – Treatment of type 2 diabetes patients with canagliflozin, an investigational drug that boosts urinary glucose excretion, produced a clear rise in glycemic control while also dropping blood pressure and weight, compared with the established agent sitagliptin, in a phase III study with 755 patients.

"This is a very nice tool to reduce hemoglobin A_1c, blood pressure, and weight all together with relatively nice results," Dr. Guntram Schernthaner said at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

The major apparent downside of canagliflozin, an inhibitor of the sodium glucose cotransporter 2 (SGLT2), was its association with a 15% rate of genital mycotic infections in women and a 9% rate in men, compared with rates of 4% in women and less than 1% in men in the comparator arm.

The benefits from canagliflozin were "impressive. It looks real," commented Dr. Bernard Zinman, director of the Center for Diabetes at Mount Sinai Hospital in Toronto.

It’s currently unclear whether the significant blood pressure and weight loss effects of the drug plus its antihyperglycemic effect will cut cardiovascular events. That’s under study, he noted, and will be a key to whether canagliflozin and other drugs in its class become major players for treating patients with diabetes. Dr. Zinman also wondered how the genital infection problem will play out for these drugs. "That will be an issue. Physicians may stay away from using it on women if one in six gets an infection," he said in an interview.

The phase III comparison between canagliflozin and sitagliptin reported by Dr. Schernthaner was one of several reports on phase III studies released during the past few months by Janssen, the company developing canagliflozin. Last May, Janssen submitted a marketing approval application to the Food and Drug Administration for the drug.

Canagliflozin is one of several SGLT2 inhibitors now under development for diabetes. They boost the amount of glucose entering urine, and also inhibit intestinal glucose absorption. Dapagliflozin, another drug from the class, also has FDA approval pending, while empagliflozin is now in several phase III studies.

Dr. Schernthaner’s findings came from 755 patients with type 2 diabetes who remained poorly controlled despite stable treatment with metformin and a sulfonylurea. Patients had an average age of 57 years, they had type 2 diabetes for an average of 10 years, their average hemoglobin A_1c was 8.1%, and their average fasting plasma glucose was 9.2 mmol/L. The researchers randomized 378 patients to receive 100 mg sitagliptin daily and 377 to received 300 mg canagliflozin daily.

After 52 weeks, hemoglobin A_1c fell an average 1.03% compared with baseline in the canagliflozin arm and 0.66% in the sitagliptin group, a statistically significant difference for the study’s primary end point, reported Dr. Schernthaner, a professor at Rudolfstiftung Hospital in Vienna.

Other statistically significant between-group differences included the drop in fasting plasma glucose, 1.7 mmol/L with canagliflozin and 0.3 mmol/L with sitagliptin, the change in body weight, an average 2.3 kg drop with canagliflozin and a 0.1 kg rise with sitagliptin, and blood pressure change, a fall of 5.3 mm Hg with canagliflozin and a +0.9/–0.3 change with sitagliptin.

Mitchel L. Zoler/IMNG Medical Media

Rates of adverse events, including serious adverse events leading to withdrawal from the study, and hypoglycemic episodes, were similar in the two treatment arms, with the only substantial difference being the excess genital mycotic infections with canagliflozin.

"The interesting question is how would an SGLT2 inhibitor act when given along with a dipeptidyl peptidase-4 inhibitor" like sitagliptin, commented Dr. Baptist J. Gallwitz, professor of diabetology and endocrinology at Tubingen University Hospital in Germany. "The SGLT-2 inhibitor drugs will be an important class because they have a distinct, independent mode of action. You can theoretically combine them with any other drug and use them at any stage of diabetes," he said in an interview.

One troubling feature of the new canagliflozin study was the high rate of patients who dropped out, 44% of those in the sitagliptin arm and 33% in the canagliflozin group. Many of the dropouts occurred when patients failed to meet prespecified glycemic targets – 23% of patients in the sitagliptin arm and 11% put on canagliflozin.

"You need to be cautious. The tremendous dropout rate is not acceptable," said Dr. Zinman. "It’s very difficult to interpret a study with that kind of dropout."

Another possible flaw in the study was using sitagliptin as the comparator on top of background treatment with another secretagogue, a sulfonylurea. It’s possible that "patients were already getting the maximum benefit from the sulfonylurea" and so couldn’t show much additional benefit from also receiving canagliflozin, Dr. Zinman said.

The study was sponsored by Janssen, the company developing canagliflozin. Dr. Schernthaner said that he has received honoraria and research funding from Janssen, AstraZeneca and Bristol-Myers Squibb, the companies developing dapagliflozin, and from Boehringer Ingelheim, the company developing empagliflozin. Dr. Zinman said that he has received honoraria and research funding from Johnson & Johnson (the parent company of Janssen), and Boehringer Ingelheim and other drug companies. Dr. Gallwitz said that he has received honoraria and research funding from Boehringer Ingelheim, AstraZeneca and Bristol-Myers Squibb, and other drug companies.

BERLIN – Insulin glargine received another epidemiologic vote of confidence that it does not cause breast cancer, this time in results from a multinational case-control study involving about 3,800 women with diabetes.

The study correlated the rates of breast cancer seen in women with diabetes with the type of insulin they used, and found "no difference in the risk of breast cancer in patients using glargine or other individual insulins," Dr. Lucien Abenhaim said at the annual meeting of the European Association for the Study of Diabetes.

The results also showed a strong association between a longer duration of diabetes and breast cancer risk. Women with diabetes for at least 10 years had a statistically significant 31% higher rate of breast cancer, compared with women who had been first diagnosed with diabetes within the preceding 10 years.

This report was the third major epidemiologic assessment of glargine and cancer to come out this year, and the third to give glargine a clean bill of health. All three studies stemmed from a research project launched by Sanofi-Aventis, the company that markets glargine (Lantus), in 2009. The launch of the project was in response to hints of a glargine and cancer association reported that year and a request for additional data on the subject from the European Medicines Agency. Researchers reported results from the two other Sanofi-sponsored studies last June at the annual meeting of the American Diabetes Association.

"I think the results we report are very strong" in ruling out a glargine and breast cancer link, Dr. Abenhaim said in an interview.

The new report "goes some way toward addressing the concern," commented Dr. Helen M. Colhoun, the designated discussant for the study, in an interview. "It provides reassurance, although the data are relatively small. I would have liked to see a really detailed analysis of cumulative exposure, but that would be difficult to do, because there have not been that many years of exposure to glargine. The investigators did the best they could," said Dr. Calhoun, an epidemiologist and professor of public health at the University of Dundee (Scotland).

The International Study of Insulin and Cancer used data on 775 women with breast cancer who were also patients with diabetes collected at 92 large breast cancer centers in the United Kingdom, France, and Canada, and data on 3,050 matched control women with diabetes but no cancer, collected from 580 primary care practices in the same three countries. All women in the study were enrolled during 2008 and the first half of 2009, and each underwent a detailed telephone interview to collect sociodemographic and lifestyle information for use in confounder adjustments.

The women averaged 66 years old, about 94% had type 2 diabetes, and about a quarter of all women used insulin. The vast majority of the breast cancers were primary invasive tumors, with 47% of the cases being stage I cancer and 30% stage II. The researchers used the women’s drug histories for the 8 years preceding enrollment, said Dr. Abenhaim, founder and chairman of LA-SER, a biomedical research consulting company based in London.

In the adjusted analysis, women treated with glargine had a 4% increased risk for breast cancer compared with women who had never received glargine, a difference that was not statistically significant. The analyses also showed no statistically significant excess or deficit of breast cancer cases among the women treated with each of the other specific insulin types assessed – lispro, aspart, and human – nor did treatment with any of the four types of insulin studied have an impact. And the analyses showed no statistical differences among any of the four insulin types.

The average duration of glargine use among the women who received the drug was 3 years, and Dr. Abenhaim and his associates also looked at the impact of increased cumulative glargine exposure, as well as increased dosage. These analyses showed no increased breast cancer among women who received glargine for 4-7 years compared with those who got it for fewer than 4 years, and also showed no apparent effect from higher glargine dosages.

The study was sponsored by Sanofi-Aventis, the company that markets glargine (Lantus). Dr. Abenhaim said that he had no other disclosures.

BERLIN – Insulin glargine received another epidemiologic vote of confidence that it does not cause breast cancer, this time in results from a multinational case-control study involving about 3,800 women with diabetes.

The study correlated the rates of breast cancer seen in women with diabetes with the type of insulin they used, and found "no difference in the risk of breast cancer in patients using glargine or other individual insulins," Dr. Lucien Abenhaim said at the annual meeting of the European Association for the Study of Diabetes.

The results also showed a strong association between a longer duration of diabetes and breast cancer risk. Women with diabetes for at least 10 years had a statistically significant 31% higher rate of breast cancer, compared with women who had been first diagnosed with diabetes within the preceding 10 years.

This report was the third major epidemiologic assessment of glargine and cancer to come out this year, and the third to give glargine a clean bill of health. All three studies stemmed from a research project launched by Sanofi-Aventis, the company that markets glargine (Lantus), in 2009. The launch of the project was in response to hints of a glargine and cancer association reported that year and a request for additional data on the subject from the European Medicines Agency. Researchers reported results from the two other Sanofi-sponsored studies last June at the annual meeting of the American Diabetes Association.

"I think the results we report are very strong" in ruling out a glargine and breast cancer link, Dr. Abenhaim said in an interview.

The new report "goes some way toward addressing the concern," commented Dr. Helen M. Colhoun, the designated discussant for the study, in an interview. "It provides reassurance, although the data are relatively small. I would have liked to see a really detailed analysis of cumulative exposure, but that would be difficult to do, because there have not been that many years of exposure to glargine. The investigators did the best they could," said Dr. Calhoun, an epidemiologist and professor of public health at the University of Dundee (Scotland).

The International Study of Insulin and Cancer used data on 775 women with breast cancer who were also patients with diabetes collected at 92 large breast cancer centers in the United Kingdom, France, and Canada, and data on 3,050 matched control women with diabetes but no cancer, collected from 580 primary care practices in the same three countries. All women in the study were enrolled during 2008 and the first half of 2009, and each underwent a detailed telephone interview to collect sociodemographic and lifestyle information for use in confounder adjustments.

The women averaged 66 years old, about 94% had type 2 diabetes, and about a quarter of all women used insulin. The vast majority of the breast cancers were primary invasive tumors, with 47% of the cases being stage I cancer and 30% stage II. The researchers used the women’s drug histories for the 8 years preceding enrollment, said Dr. Abenhaim, founder and chairman of LA-SER, a biomedical research consulting company based in London.

In the adjusted analysis, women treated with glargine had a 4% increased risk for breast cancer compared with women who had never received glargine, a difference that was not statistically significant. The analyses also showed no statistically significant excess or deficit of breast cancer cases among the women treated with each of the other specific insulin types assessed – lispro, aspart, and human – nor did treatment with any of the four types of insulin studied have an impact. And the analyses showed no statistical differences among any of the four insulin types.

The average duration of glargine use among the women who received the drug was 3 years, and Dr. Abenhaim and his associates also looked at the impact of increased cumulative glargine exposure, as well as increased dosage. These analyses showed no increased breast cancer among women who received glargine for 4-7 years compared with those who got it for fewer than 4 years, and also showed no apparent effect from higher glargine dosages.

The study was sponsored by Sanofi-Aventis, the company that markets glargine (Lantus). Dr. Abenhaim said that he had no other disclosures.

BERLIN – Insulin glargine received another epidemiologic vote of confidence that it does not cause breast cancer, this time in results from a multinational case-control study involving about 3,800 women with diabetes.

The study correlated the rates of breast cancer seen in women with diabetes with the type of insulin they used, and found "no difference in the risk of breast cancer in patients using glargine or other individual insulins," Dr. Lucien Abenhaim said at the annual meeting of the European Association for the Study of Diabetes.

The results also showed a strong association between a longer duration of diabetes and breast cancer risk. Women with diabetes for at least 10 years had a statistically significant 31% higher rate of breast cancer, compared with women who had been first diagnosed with diabetes within the preceding 10 years.

This report was the third major epidemiologic assessment of glargine and cancer to come out this year, and the third to give glargine a clean bill of health. All three studies stemmed from a research project launched by Sanofi-Aventis, the company that markets glargine (Lantus), in 2009. The launch of the project was in response to hints of a glargine and cancer association reported that year and a request for additional data on the subject from the European Medicines Agency. Researchers reported results from the two other Sanofi-sponsored studies last June at the annual meeting of the American Diabetes Association.

"I think the results we report are very strong" in ruling out a glargine and breast cancer link, Dr. Abenhaim said in an interview.

The new report "goes some way toward addressing the concern," commented Dr. Helen M. Colhoun, the designated discussant for the study, in an interview. "It provides reassurance, although the data are relatively small. I would have liked to see a really detailed analysis of cumulative exposure, but that would be difficult to do, because there have not been that many years of exposure to glargine. The investigators did the best they could," said Dr. Calhoun, an epidemiologist and professor of public health at the University of Dundee (Scotland).

The International Study of Insulin and Cancer used data on 775 women with breast cancer who were also patients with diabetes collected at 92 large breast cancer centers in the United Kingdom, France, and Canada, and data on 3,050 matched control women with diabetes but no cancer, collected from 580 primary care practices in the same three countries. All women in the study were enrolled during 2008 and the first half of 2009, and each underwent a detailed telephone interview to collect sociodemographic and lifestyle information for use in confounder adjustments.

The women averaged 66 years old, about 94% had type 2 diabetes, and about a quarter of all women used insulin. The vast majority of the breast cancers were primary invasive tumors, with 47% of the cases being stage I cancer and 30% stage II. The researchers used the women’s drug histories for the 8 years preceding enrollment, said Dr. Abenhaim, founder and chairman of LA-SER, a biomedical research consulting company based in London.

In the adjusted analysis, women treated with glargine had a 4% increased risk for breast cancer compared with women who had never received glargine, a difference that was not statistically significant. The analyses also showed no statistically significant excess or deficit of breast cancer cases among the women treated with each of the other specific insulin types assessed – lispro, aspart, and human – nor did treatment with any of the four types of insulin studied have an impact. And the analyses showed no statistical differences among any of the four insulin types.

The average duration of glargine use among the women who received the drug was 3 years, and Dr. Abenhaim and his associates also looked at the impact of increased cumulative glargine exposure, as well as increased dosage. These analyses showed no increased breast cancer among women who received glargine for 4-7 years compared with those who got it for fewer than 4 years, and also showed no apparent effect from higher glargine dosages.

The study was sponsored by Sanofi-Aventis, the company that markets glargine (Lantus). Dr. Abenhaim said that he had no other disclosures.

BERLIN – Older patients with type 2 diabetes are very likely to have left ventricular dysfunction, even in the absence of any sign of cardiac disease.

However, at least some of this dysfunction can remit over time, perhaps as a result of effective diabetes treatment, Dr. Carlo Bruno Giorda said at the annual meeting of the European Association for the Study of Diabetes.

Dr. Giorda reported results of Left Ventricular Dysfunction in Diabetes (DYDA), a 2-year prospective study that tracked the development of left ventricular dysfunction in 957 patients with type 2 diabetes who did not have any signs of cardiac disease at baseline.

DYDA’s secondary end point was a combination of all-cause mortality and cardiovascular hospitalization; the study also sought to identify factors predicting these outcomes, said Dr. Giorda of the Ospedale Maggiore, Chieri, Italy.

The study defined left ventricular systolic dysfunction as an ejection fraction of less than 50% and/or a midwall fractional shortening of 15% or less. At baseline, all patients underwent an echocardiogram to determine left ventricular dysfunction. Imaging revealed that 60% of the cohort had some form of LVD – systolic (21%), diastolic (27%), or both (12%).

The patients were a mean of 61 years; 62% were men. Almost half (44%) were overweight and 35% were obese. The median heart rate was 72 beats per minute. The median blood pressure was 137/80.

Diabetes medications included sulfonylureas (43%), insulin (32%), repaglinide (11%), metformin (66%), acarbose (2%), and glitazones (5%). Most patients (60%) were hypertensive and being treated for that; 55% were taking medication for dyslipidemia.

Comorbidities included vascular disease (8%), diabetic retinopathy (13%), diabetic neuropathy (8%), and thyroid disease (8%). Others were chronic obstructive pulmonary disease (3%) and chronic kidney disease (2%).

Diabetes was well-controlled in the group, Dr. Giorda said. The median hemoglobin A_1c was 6.7%, and the median blood glucose 142 mg/dL. The median creatinine level was 0.90 mg/dL, and the median glomerular filtration rate, 84 mL/min.

By the 2-year mark, 15 patients had died; only 3 of these deaths were attributed to cardiovascular causes. Eleven patients had died of non-cardiovascular issues, and one death occurred of unknown etiology. There had been 181 hospitalizations among 139 patients. The majority of these (133) were for non–cardiovascular problems.

Dr. Giorda said the association with repaglinide was probably a chance finding. "We even controlled for renal insufficiency, since repaglinide is often used for those patients in Italy, and this relationship still emerged."

At the end of the study period, new onset systolic dysfunction had developed in 17% and diastolic in 22% of the initially negative group.

A multivariate analysis identified several baseline factors that significantly predicted the development of LVD, including age (67 years vs. 56 years), HbA_1c (7.6% vs. 6%), and heart rate (90 vs. 68 beats per minute.

A surprise finding, however, was that LVD remitted in several patients, Dr. Giorda said. "There was reversal of LVD in 12% of the patients who had it at baseline. We can’t say why it reversed ... maybe it was due to [diabetes treatment]. But we can say that in some patients, LVD can be considered temporary."

Dr. Giorda had no financial disclosures.

BERLIN – Older patients with type 2 diabetes are very likely to have left ventricular dysfunction, even in the absence of any sign of cardiac disease.

However, at least some of this dysfunction can remit over time, perhaps as a result of effective diabetes treatment, Dr. Carlo Bruno Giorda said at the annual meeting of the European Association for the Study of Diabetes.

Dr. Giorda reported results of Left Ventricular Dysfunction in Diabetes (DYDA), a 2-year prospective study that tracked the development of left ventricular dysfunction in 957 patients with type 2 diabetes who did not have any signs of cardiac disease at baseline.

DYDA’s secondary end point was a combination of all-cause mortality and cardiovascular hospitalization; the study also sought to identify factors predicting these outcomes, said Dr. Giorda of the Ospedale Maggiore, Chieri, Italy.

The study defined left ventricular systolic dysfunction as an ejection fraction of less than 50% and/or a midwall fractional shortening of 15% or less. At baseline, all patients underwent an echocardiogram to determine left ventricular dysfunction. Imaging revealed that 60% of the cohort had some form of LVD – systolic (21%), diastolic (27%), or both (12%).

The patients were a mean of 61 years; 62% were men. Almost half (44%) were overweight and 35% were obese. The median heart rate was 72 beats per minute. The median blood pressure was 137/80.

Diabetes medications included sulfonylureas (43%), insulin (32%), repaglinide (11%), metformin (66%), acarbose (2%), and glitazones (5%). Most patients (60%) were hypertensive and being treated for that; 55% were taking medication for dyslipidemia.

Comorbidities included vascular disease (8%), diabetic retinopathy (13%), diabetic neuropathy (8%), and thyroid disease (8%). Others were chronic obstructive pulmonary disease (3%) and chronic kidney disease (2%).

Diabetes was well-controlled in the group, Dr. Giorda said. The median hemoglobin A_1c was 6.7%, and the median blood glucose 142 mg/dL. The median creatinine level was 0.90 mg/dL, and the median glomerular filtration rate, 84 mL/min.

By the 2-year mark, 15 patients had died; only 3 of these deaths were attributed to cardiovascular causes. Eleven patients had died of non-cardiovascular issues, and one death occurred of unknown etiology. There had been 181 hospitalizations among 139 patients. The majority of these (133) were for non–cardiovascular problems.

Dr. Giorda said the association with repaglinide was probably a chance finding. "We even controlled for renal insufficiency, since repaglinide is often used for those patients in Italy, and this relationship still emerged."

At the end of the study period, new onset systolic dysfunction had developed in 17% and diastolic in 22% of the initially negative group.

A multivariate analysis identified several baseline factors that significantly predicted the development of LVD, including age (67 years vs. 56 years), HbA_1c (7.6% vs. 6%), and heart rate (90 vs. 68 beats per minute.

A surprise finding, however, was that LVD remitted in several patients, Dr. Giorda said. "There was reversal of LVD in 12% of the patients who had it at baseline. We can’t say why it reversed ... maybe it was due to [diabetes treatment]. But we can say that in some patients, LVD can be considered temporary."

Dr. Giorda had no financial disclosures.

BERLIN – Older patients with type 2 diabetes are very likely to have left ventricular dysfunction, even in the absence of any sign of cardiac disease.

However, at least some of this dysfunction can remit over time, perhaps as a result of effective diabetes treatment, Dr. Carlo Bruno Giorda said at the annual meeting of the European Association for the Study of Diabetes.

Dr. Giorda reported results of Left Ventricular Dysfunction in Diabetes (DYDA), a 2-year prospective study that tracked the development of left ventricular dysfunction in 957 patients with type 2 diabetes who did not have any signs of cardiac disease at baseline.

DYDA’s secondary end point was a combination of all-cause mortality and cardiovascular hospitalization; the study also sought to identify factors predicting these outcomes, said Dr. Giorda of the Ospedale Maggiore, Chieri, Italy.

The study defined left ventricular systolic dysfunction as an ejection fraction of less than 50% and/or a midwall fractional shortening of 15% or less. At baseline, all patients underwent an echocardiogram to determine left ventricular dysfunction. Imaging revealed that 60% of the cohort had some form of LVD – systolic (21%), diastolic (27%), or both (12%).

The patients were a mean of 61 years; 62% were men. Almost half (44%) were overweight and 35% were obese. The median heart rate was 72 beats per minute. The median blood pressure was 137/80.

Diabetes medications included sulfonylureas (43%), insulin (32%), repaglinide (11%), metformin (66%), acarbose (2%), and glitazones (5%). Most patients (60%) were hypertensive and being treated for that; 55% were taking medication for dyslipidemia.

Comorbidities included vascular disease (8%), diabetic retinopathy (13%), diabetic neuropathy (8%), and thyroid disease (8%). Others were chronic obstructive pulmonary disease (3%) and chronic kidney disease (2%).

Diabetes was well-controlled in the group, Dr. Giorda said. The median hemoglobin A_1c was 6.7%, and the median blood glucose 142 mg/dL. The median creatinine level was 0.90 mg/dL, and the median glomerular filtration rate, 84 mL/min.

By the 2-year mark, 15 patients had died; only 3 of these deaths were attributed to cardiovascular causes. Eleven patients had died of non-cardiovascular issues, and one death occurred of unknown etiology. There had been 181 hospitalizations among 139 patients. The majority of these (133) were for non–cardiovascular problems.

Dr. Giorda said the association with repaglinide was probably a chance finding. "We even controlled for renal insufficiency, since repaglinide is often used for those patients in Italy, and this relationship still emerged."

At the end of the study period, new onset systolic dysfunction had developed in 17% and diastolic in 22% of the initially negative group.

A multivariate analysis identified several baseline factors that significantly predicted the development of LVD, including age (67 years vs. 56 years), HbA_1c (7.6% vs. 6%), and heart rate (90 vs. 68 beats per minute.

A surprise finding, however, was that LVD remitted in several patients, Dr. Giorda said. "There was reversal of LVD in 12% of the patients who had it at baseline. We can’t say why it reversed ... maybe it was due to [diabetes treatment]. But we can say that in some patients, LVD can be considered temporary."

Dr. Giorda had no financial disclosures.

BERLIN – A population-based screening project for type 2 diabetes did not improve 10-year mortality, a very large British study has determined.

When compared to best-practice identification of individual diabetes patients, general screening offered no benefits in all-cause mortality or in the specific outcomes of cardiovascular, cancer, or diabetes-related deaths Dr. Rebecca K. Simmons reported Oct. 4 at the annual meeting of the European Association for the Study of Diabetes (EASD).

But the study did show that individuals at risk for the disease who refused the screening were significantly more likely to die over the follow-up period, said Dr. Simmons of the University of Cambridge (England).

"The take-home message here is that the benefits of population-based screening have been overestimated and are probably restricted to those who are at risk, who attend the screen, and who receive earlier treatment because of it," she said.

The ADDITION-Cambridge study involved 32 general medical practices in England and more than 20,000 patients who were at risk of developing type 2 diabetes. The practices were randomized to conduct either large-scale screening of all at-risk patients (27) or to no screening (5). The control practices continued to diagnose patients according to best practices.

Practices in the intervention group sent invitations to those who had been identified as high risk. The stepwise process included capillary blood glucose and hemoglobin A_1c tests, and a confirmatory oral glucose tolerance test. Those who had the OGTT also had a cardiovascular risk factor assessment that included body mass index, waist circumference, blood pressure, and lipids. Those who did not attend the screen after a reminder were considered to be nonattenders.

Patients diagnosed in either practice group were managed according to a national consensus guideline of lifestyle education and modification, medical management, and blood pressure and cholesterol control.

All participants – whether screened or not – were followed for 10 years in the National Office of Statistics. The study accumulated 184,000 person-years of follow-up data.

Of the 16,000 screen-eligible patients, 15,000 were invited for screening and 11,737 (73%) attended the first stage. There were 466 new diagnoses of type 2 diabetes (3% of the screen-eligible group). There were 4,137 patients in the no-screening group, who served as controls.

Patients had a mean age of 58 years; most (64%) were male. The mean BMI was 30.5 kg/m². About half were taking an antihypertensive, and a small number (4%-5%) were taking steroids.

At 10 years, there were 1,532 deaths in the screening group (10.5 per 1,000 person-years), and 377 in the control group (9.9 per 1,000 person-years) – a difference that was not significant.

The screening group had 482 cardiovascular deaths (3.3 per 1,000 person-years), compared with 124 in the control group (3.3 per 1,000 person-years). Cancer was the cause of death in 697 patients in the screening group and in 169 in the control group (4.8 and 4.4 per 1,000 person-years, respectively). Diabetes-related deaths occurred in 75 of the screening group and in 16 of the control group (0.5 and 0.4 per 1,000 person-years).

Deaths due to other causes occurred in 353 patients in the screening group (2.4 per 1,000 person-years) and 84 in the control group (2.2 per 1,000 person-years).

None of these findings were statistically significant, Dr. Simmons said.

However, a significant difference did emerge when the invited group was broken down into attenders and nonattenders. In this analysis, those who refused screening were 62% more likely to die within 10 years, and those who attended were 17% less likely to die, than were the control patients.

Most of those who refused screening were younger, obese men, who were less likely to be taking antihypertensive medications. Considered along with the significant increase in the risk of death in this group, targeted screening makes more sense than a general approach, Dr. Simmons suggested.

The results of ADDITION-Cambridge were published online to coincide with the EASD meeting (Lancet 2012 Oct. 4 [doi: 10.1016/S0140-6736(12)61422-6]).

"It’s probably best to focus on identifying those who have diagnosable disease and treating them according to our best practices," she said.

The study was funded by the Wellcome Trust, the Medical Research Council, the National Health Service, and the National Institute for Health Research. Dr. Simmons had no financial disclosures.

BERLIN – A population-based screening project for type 2 diabetes did not improve 10-year mortality, a very large British study has determined.

When compared to best-practice identification of individual diabetes patients, general screening offered no benefits in all-cause mortality or in the specific outcomes of cardiovascular, cancer, or diabetes-related deaths Dr. Rebecca K. Simmons reported Oct. 4 at the annual meeting of the European Association for the Study of Diabetes (EASD).

But the study did show that individuals at risk for the disease who refused the screening were significantly more likely to die over the follow-up period, said Dr. Simmons of the University of Cambridge (England).

"The take-home message here is that the benefits of population-based screening have been overestimated and are probably restricted to those who are at risk, who attend the screen, and who receive earlier treatment because of it," she said.

The ADDITION-Cambridge study involved 32 general medical practices in England and more than 20,000 patients who were at risk of developing type 2 diabetes. The practices were randomized to conduct either large-scale screening of all at-risk patients (27) or to no screening (5). The control practices continued to diagnose patients according to best practices.

Practices in the intervention group sent invitations to those who had been identified as high risk. The stepwise process included capillary blood glucose and hemoglobin A_1c tests, and a confirmatory oral glucose tolerance test. Those who had the OGTT also had a cardiovascular risk factor assessment that included body mass index, waist circumference, blood pressure, and lipids. Those who did not attend the screen after a reminder were considered to be nonattenders.

Patients diagnosed in either practice group were managed according to a national consensus guideline of lifestyle education and modification, medical management, and blood pressure and cholesterol control.

All participants – whether screened or not – were followed for 10 years in the National Office of Statistics. The study accumulated 184,000 person-years of follow-up data.

Of the 16,000 screen-eligible patients, 15,000 were invited for screening and 11,737 (73%) attended the first stage. There were 466 new diagnoses of type 2 diabetes (3% of the screen-eligible group). There were 4,137 patients in the no-screening group, who served as controls.

Patients had a mean age of 58 years; most (64%) were male. The mean BMI was 30.5 kg/m². About half were taking an antihypertensive, and a small number (4%-5%) were taking steroids.

At 10 years, there were 1,532 deaths in the screening group (10.5 per 1,000 person-years), and 377 in the control group (9.9 per 1,000 person-years) – a difference that was not significant.

The screening group had 482 cardiovascular deaths (3.3 per 1,000 person-years), compared with 124 in the control group (3.3 per 1,000 person-years). Cancer was the cause of death in 697 patients in the screening group and in 169 in the control group (4.8 and 4.4 per 1,000 person-years, respectively). Diabetes-related deaths occurred in 75 of the screening group and in 16 of the control group (0.5 and 0.4 per 1,000 person-years).

Deaths due to other causes occurred in 353 patients in the screening group (2.4 per 1,000 person-years) and 84 in the control group (2.2 per 1,000 person-years).

None of these findings were statistically significant, Dr. Simmons said.

However, a significant difference did emerge when the invited group was broken down into attenders and nonattenders. In this analysis, those who refused screening were 62% more likely to die within 10 years, and those who attended were 17% less likely to die, than were the control patients.

Most of those who refused screening were younger, obese men, who were less likely to be taking antihypertensive medications. Considered along with the significant increase in the risk of death in this group, targeted screening makes more sense than a general approach, Dr. Simmons suggested.

The results of ADDITION-Cambridge were published online to coincide with the EASD meeting (Lancet 2012 Oct. 4 [doi: 10.1016/S0140-6736(12)61422-6]).

"It’s probably best to focus on identifying those who have diagnosable disease and treating them according to our best practices," she said.

The study was funded by the Wellcome Trust, the Medical Research Council, the National Health Service, and the National Institute for Health Research. Dr. Simmons had no financial disclosures.

BERLIN – A population-based screening project for type 2 diabetes did not improve 10-year mortality, a very large British study has determined.

When compared to best-practice identification of individual diabetes patients, general screening offered no benefits in all-cause mortality or in the specific outcomes of cardiovascular, cancer, or diabetes-related deaths Dr. Rebecca K. Simmons reported Oct. 4 at the annual meeting of the European Association for the Study of Diabetes (EASD).

But the study did show that individuals at risk for the disease who refused the screening were significantly more likely to die over the follow-up period, said Dr. Simmons of the University of Cambridge (England).

"The take-home message here is that the benefits of population-based screening have been overestimated and are probably restricted to those who are at risk, who attend the screen, and who receive earlier treatment because of it," she said.

The ADDITION-Cambridge study involved 32 general medical practices in England and more than 20,000 patients who were at risk of developing type 2 diabetes. The practices were randomized to conduct either large-scale screening of all at-risk patients (27) or to no screening (5). The control practices continued to diagnose patients according to best practices.

Practices in the intervention group sent invitations to those who had been identified as high risk. The stepwise process included capillary blood glucose and hemoglobin A_1c tests, and a confirmatory oral glucose tolerance test. Those who had the OGTT also had a cardiovascular risk factor assessment that included body mass index, waist circumference, blood pressure, and lipids. Those who did not attend the screen after a reminder were considered to be nonattenders.

Patients diagnosed in either practice group were managed according to a national consensus guideline of lifestyle education and modification, medical management, and blood pressure and cholesterol control.

All participants – whether screened or not – were followed for 10 years in the National Office of Statistics. The study accumulated 184,000 person-years of follow-up data.

Of the 16,000 screen-eligible patients, 15,000 were invited for screening and 11,737 (73%) attended the first stage. There were 466 new diagnoses of type 2 diabetes (3% of the screen-eligible group). There were 4,137 patients in the no-screening group, who served as controls.

Patients had a mean age of 58 years; most (64%) were male. The mean BMI was 30.5 kg/m². About half were taking an antihypertensive, and a small number (4%-5%) were taking steroids.

At 10 years, there were 1,532 deaths in the screening group (10.5 per 1,000 person-years), and 377 in the control group (9.9 per 1,000 person-years) – a difference that was not significant.

The screening group had 482 cardiovascular deaths (3.3 per 1,000 person-years), compared with 124 in the control group (3.3 per 1,000 person-years). Cancer was the cause of death in 697 patients in the screening group and in 169 in the control group (4.8 and 4.4 per 1,000 person-years, respectively). Diabetes-related deaths occurred in 75 of the screening group and in 16 of the control group (0.5 and 0.4 per 1,000 person-years).

Deaths due to other causes occurred in 353 patients in the screening group (2.4 per 1,000 person-years) and 84 in the control group (2.2 per 1,000 person-years).

None of these findings were statistically significant, Dr. Simmons said.

However, a significant difference did emerge when the invited group was broken down into attenders and nonattenders. In this analysis, those who refused screening were 62% more likely to die within 10 years, and those who attended were 17% less likely to die, than were the control patients.

Most of those who refused screening were younger, obese men, who were less likely to be taking antihypertensive medications. Considered along with the significant increase in the risk of death in this group, targeted screening makes more sense than a general approach, Dr. Simmons suggested.

The results of ADDITION-Cambridge were published online to coincide with the EASD meeting (Lancet 2012 Oct. 4 [doi: 10.1016/S0140-6736(12)61422-6]).

"It’s probably best to focus on identifying those who have diagnosable disease and treating them according to our best practices," she said.

The study was funded by the Wellcome Trust, the Medical Research Council, the National Health Service, and the National Institute for Health Research. Dr. Simmons had no financial disclosures.

BERLIN – Intermittent use of continuous glucose monitoring during pregnancy failed to improve glycemic control or cut the rate of neonatal macrosomia in a single-center, randomized study with 149 women with diabetes.

In fact, the rate of macrosomia was actually higher in the 76 women with diabetes who used continuous, real-time glucose monitoring during at least 5 weeks of their pregnancy, with a 45% rate, compared with a 34% rate among the 73 control women who used seven-per-day sessions of self-monitoring throughout their pregnancy, a difference that was not statistically significant, Dr. Anna L. Secher said at the meeting.

Mitchel L. Zoler/IMNG Medical Media

The absence of any discernable benefit from real-time continuous monitoring for any of the measures examined set back the concept that pregnancy could benefit from continuous monitoring, as shown in a prior study of intermittent, continuous monitoring from other investigators (BMJ 2008;337:a1680).

"We were surprised and disappointed with the results," said Dr. Secher, a researcher with the center for pregnant women with diabetes at Rigshospitalet in Copenhagen. The absence of any significant effect from continuous monitoring on macrosomia, prematurity, or episodes of severe neonatal hypoglycemia may have resulted from a cautious control approach promoted by the center’s staff in an effort to minimize hypoglycemia events.

"By focusing on severe hypoglycemia, we might pay a price in hyperglycemic complications," she said.

Another flaw in the Danish study was that the study protocol specified continuous monitoring during only gestational weeks 8, 12, 21, 27, and 33, with each of these weeks culminating with a clinic visit and adjustments to insulin dosages and diet as dictated by the monitoring results. Women in the continuous-monitoring arm were "encouraged" to use continuous monitoring as often as they could during the rest of their pregnancy, but it was not mandatory.

"We made the design intermittent because we knew that limitations in the system would affect compliance," Dr. Secher said. In addition, "we were concerned that women who could use continuous monitoring would be a selected population with limited numbers."

The study enrolled women with type 1 or 2 diabetes at less than 14 weeks’ gestation with a singleton pregnancy. Their average hemoglobin A_1c at baseline was about 6.7%, their average body mass index was about 25 kg/m², and their average duration of diabetes was about 11 years. Eighty percent had type 1 diabetes.

The 76 women who completed the continuous-monitoring arm of the study used the Guardian monitor marketed by Medtronic.

The measurements taken during pregnancy showed identical average levels of HbA_1c in both treatment arms throughout the study. The rate of preterm delivery, severe neonatal hypoglycemia, or both was 29% in the continuous-monitoring women and 22% in those who always self-monitored.

A subgroup analysis that focused on the 80% of women with type 1 diabetes failed to change the outcomes. In addition, 22% of the women in the continuous-monitoring group also used an insulin pump, and for these women their pump was hooked up to their continuous monitor. An additional subgroup analysis that focused only on these women also failed to change the outcomes.

Dr. Secher said that she and her associates had no disclosures.

BERLIN – Intermittent use of continuous glucose monitoring during pregnancy failed to improve glycemic control or cut the rate of neonatal macrosomia in a single-center, randomized study with 149 women with diabetes.

In fact, the rate of macrosomia was actually higher in the 76 women with diabetes who used continuous, real-time glucose monitoring during at least 5 weeks of their pregnancy, with a 45% rate, compared with a 34% rate among the 73 control women who used seven-per-day sessions of self-monitoring throughout their pregnancy, a difference that was not statistically significant, Dr. Anna L. Secher said at the meeting.

Mitchel L. Zoler/IMNG Medical Media

The absence of any discernable benefit from real-time continuous monitoring for any of the measures examined set back the concept that pregnancy could benefit from continuous monitoring, as shown in a prior study of intermittent, continuous monitoring from other investigators (BMJ 2008;337:a1680).

"We were surprised and disappointed with the results," said Dr. Secher, a researcher with the center for pregnant women with diabetes at Rigshospitalet in Copenhagen. The absence of any significant effect from continuous monitoring on macrosomia, prematurity, or episodes of severe neonatal hypoglycemia may have resulted from a cautious control approach promoted by the center’s staff in an effort to minimize hypoglycemia events.

"By focusing on severe hypoglycemia, we might pay a price in hyperglycemic complications," she said.

Another flaw in the Danish study was that the study protocol specified continuous monitoring during only gestational weeks 8, 12, 21, 27, and 33, with each of these weeks culminating with a clinic visit and adjustments to insulin dosages and diet as dictated by the monitoring results. Women in the continuous-monitoring arm were "encouraged" to use continuous monitoring as often as they could during the rest of their pregnancy, but it was not mandatory.

"We made the design intermittent because we knew that limitations in the system would affect compliance," Dr. Secher said. In addition, "we were concerned that women who could use continuous monitoring would be a selected population with limited numbers."

The study enrolled women with type 1 or 2 diabetes at less than 14 weeks’ gestation with a singleton pregnancy. Their average hemoglobin A_1c at baseline was about 6.7%, their average body mass index was about 25 kg/m², and their average duration of diabetes was about 11 years. Eighty percent had type 1 diabetes.

The 76 women who completed the continuous-monitoring arm of the study used the Guardian monitor marketed by Medtronic.

The measurements taken during pregnancy showed identical average levels of HbA_1c in both treatment arms throughout the study. The rate of preterm delivery, severe neonatal hypoglycemia, or both was 29% in the continuous-monitoring women and 22% in those who always self-monitored.

A subgroup analysis that focused on the 80% of women with type 1 diabetes failed to change the outcomes. In addition, 22% of the women in the continuous-monitoring group also used an insulin pump, and for these women their pump was hooked up to their continuous monitor. An additional subgroup analysis that focused only on these women also failed to change the outcomes.

Dr. Secher said that she and her associates had no disclosures.

BERLIN – Intermittent use of continuous glucose monitoring during pregnancy failed to improve glycemic control or cut the rate of neonatal macrosomia in a single-center, randomized study with 149 women with diabetes.

In fact, the rate of macrosomia was actually higher in the 76 women with diabetes who used continuous, real-time glucose monitoring during at least 5 weeks of their pregnancy, with a 45% rate, compared with a 34% rate among the 73 control women who used seven-per-day sessions of self-monitoring throughout their pregnancy, a difference that was not statistically significant, Dr. Anna L. Secher said at the meeting.

Mitchel L. Zoler/IMNG Medical Media

The absence of any discernable benefit from real-time continuous monitoring for any of the measures examined set back the concept that pregnancy could benefit from continuous monitoring, as shown in a prior study of intermittent, continuous monitoring from other investigators (BMJ 2008;337:a1680).

"We were surprised and disappointed with the results," said Dr. Secher, a researcher with the center for pregnant women with diabetes at Rigshospitalet in Copenhagen. The absence of any significant effect from continuous monitoring on macrosomia, prematurity, or episodes of severe neonatal hypoglycemia may have resulted from a cautious control approach promoted by the center’s staff in an effort to minimize hypoglycemia events.

"By focusing on severe hypoglycemia, we might pay a price in hyperglycemic complications," she said.

Another flaw in the Danish study was that the study protocol specified continuous monitoring during only gestational weeks 8, 12, 21, 27, and 33, with each of these weeks culminating with a clinic visit and adjustments to insulin dosages and diet as dictated by the monitoring results. Women in the continuous-monitoring arm were "encouraged" to use continuous monitoring as often as they could during the rest of their pregnancy, but it was not mandatory.

"We made the design intermittent because we knew that limitations in the system would affect compliance," Dr. Secher said. In addition, "we were concerned that women who could use continuous monitoring would be a selected population with limited numbers."

The study enrolled women with type 1 or 2 diabetes at less than 14 weeks’ gestation with a singleton pregnancy. Their average hemoglobin A_1c at baseline was about 6.7%, their average body mass index was about 25 kg/m², and their average duration of diabetes was about 11 years. Eighty percent had type 1 diabetes.

The 76 women who completed the continuous-monitoring arm of the study used the Guardian monitor marketed by Medtronic.

The measurements taken during pregnancy showed identical average levels of HbA_1c in both treatment arms throughout the study. The rate of preterm delivery, severe neonatal hypoglycemia, or both was 29% in the continuous-monitoring women and 22% in those who always self-monitored.

A subgroup analysis that focused on the 80% of women with type 1 diabetes failed to change the outcomes. In addition, 22% of the women in the continuous-monitoring group also used an insulin pump, and for these women their pump was hooked up to their continuous monitor. An additional subgroup analysis that focused only on these women also failed to change the outcomes.

Dr. Secher said that she and her associates had no disclosures.

BERLIN – Women who are diagnosed with diabetes at the time of an acute myocardial infarction are three times more likely to die over the next 3 years as are similar women without diabetes.

In contrast, men whose diabetes was diagnosed during their hospitalization for acute MI had twice the risk of death after 3 years compared with men without diabetes, based on the latest results of the SWEETHEART registry, a prospective study of 2,767 patients with ST- or non-ST-elevation myocardial infarction.

Michele G. Sullivan/IMNG Medical Media

The double-whammy of diabetes and coronary artery disease is "extraordinarily dangerous" for women, said Dr. Diethelm Tschoepe of the Heart and Diabetes Center, Bad Oeynhausen, Germany. Women with a new diagnosis of diabetes "have a much, much worse prognostic gradient" than do men with newly diagnosed diabetes, and men and women without diabetes.

Dr. Tschoepe said the findings suggest there is a large population of women with longstanding, undiagnosed diabetes that goes unrecognized until a cardiovascular event. "The vigilance of women and their treatment physicians seems to be insufficient" to detect their diabetes.

Additionally, testing for diabetes needs to occur in all patients who experience a cardiovascular event, despite the logistic difficulty this might present, Dr. Tschoepe said. "I am working in a place where endocrinologists, cardiac surgeons, and cardiologists work together, but it is still a tough fight to get every patient tested."

Among women in the study, the 3-year mortality rate was 30% for those with known diabetes and 30.5% for those with newly diagnosed diabetes – significantly higher than the rates for those without diabetes and those with impaired glucose regulation (11% and 13% respectively).

Among men, the mortality rate was highest among those with known diabetes (35%), followed by those with newly diagnosed disease (22%). Both groups had significantly higher mortality than that seen in those without diabetes and those with impaired glucose regulation (11% each).

In the overall multivariate adjusted model, patients with known diabetes were 77% more likely to die and 68% more likely to experience a major cardiovascular or cerebrovascular event than were those without diabetes. Those with newly diagnosed diabetes were 43% more likely to die and 18% more likely to have a significant adverse event than were those without diabetes, Dr. Tschoepe reported at the annual meeting of the European Association for the Study of Diabetes.

At the time of their coronary events, some level of glycemic dysregulation affected 68% of the women and 60% of the men in the study.

At admission, 30% of women and 23% of men had diabetes. Testing identified diabetes in an additional 20% of women and 15% of men. Another 18% of women and 23% of men had impaired glucose tolerance or impaired fasting glucose.

There was a "striking difference" in diabetes treatment between the groups at discharge, Dr. Tschoepe said, with 47% of women and 37% of men on some form of therapy. Oral treatment was prescribed for 27% of the women and 37% of the men, while 39% of the women and 27% of the men were discharged on insulin; both of these differences were significant. Exactly the same number of men and women were discharged on the combination of insulin and oral therapy (6.2%).

Men were more likely to be discharged on dietary treatment alone (42% vs. 39%), but this was not a significant difference. Dr. Tschoepe added.

Patients were enrolled in the trial within 24 hours of treatment and followed for 3 years. In addition to cardiovascular treatment, all patients underwent an oral glucose tolerance test as recommended in 2007 by the European Society of Cardiology and the European Association for the Study of Diabetes.

There were 706 women in the cohort. The women were older than the men, average age 71 and 64 years, respectively; were less likely to have a prior MI, 13% vs. 19%; had fewer prior percutaneous coronary interventions, 12% vs. 18%; had more hypertension, 80% vs. 69%; were less likely to smoke, 25% vs. 40%; and were more likely to have a known history of diabetes, 30% vs. 23%.

The mean blood glucose value at admission was significantly higher in women than in men, 137 mg/dL vs. 127 mg/dL. Women also had a significantly higher HbA_1c, 6.1% vs. 5.8%. STEMI and NSTEMI were equally distributed in men and women.

Almost all of the patients underwent a coronary angiogram (95% of women, 97% of men). One-, two-, and three-vessel disease were equally distributed in both genders. Cardiovascular drug therapy did not significantly differ at discharge, with the vast majority receiving aspirin, clopidogrel, beta-blockers and ACE inhibitors as appropriate with guideline recommendations.

The SWEETHEART registry is funded by Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, Sanofi, and Novartis. Dr. Tschoepe Tschoepe has received consultancy and speaker remuneration from Astra Zeneca, Bristol-Myers, Squibb, Servier, Sanofi, and Novartis.

BERLIN – Women who are diagnosed with diabetes at the time of an acute myocardial infarction are three times more likely to die over the next 3 years as are similar women without diabetes.

In contrast, men whose diabetes was diagnosed during their hospitalization for acute MI had twice the risk of death after 3 years compared with men without diabetes, based on the latest results of the SWEETHEART registry, a prospective study of 2,767 patients with ST- or non-ST-elevation myocardial infarction.

Michele G. Sullivan/IMNG Medical Media

The double-whammy of diabetes and coronary artery disease is "extraordinarily dangerous" for women, said Dr. Diethelm Tschoepe of the Heart and Diabetes Center, Bad Oeynhausen, Germany. Women with a new diagnosis of diabetes "have a much, much worse prognostic gradient" than do men with newly diagnosed diabetes, and men and women without diabetes.

Dr. Tschoepe said the findings suggest there is a large population of women with longstanding, undiagnosed diabetes that goes unrecognized until a cardiovascular event. "The vigilance of women and their treatment physicians seems to be insufficient" to detect their diabetes.

Additionally, testing for diabetes needs to occur in all patients who experience a cardiovascular event, despite the logistic difficulty this might present, Dr. Tschoepe said. "I am working in a place where endocrinologists, cardiac surgeons, and cardiologists work together, but it is still a tough fight to get every patient tested."

Among women in the study, the 3-year mortality rate was 30% for those with known diabetes and 30.5% for those with newly diagnosed diabetes – significantly higher than the rates for those without diabetes and those with impaired glucose regulation (11% and 13% respectively).

Among men, the mortality rate was highest among those with known diabetes (35%), followed by those with newly diagnosed disease (22%). Both groups had significantly higher mortality than that seen in those without diabetes and those with impaired glucose regulation (11% each).

In the overall multivariate adjusted model, patients with known diabetes were 77% more likely to die and 68% more likely to experience a major cardiovascular or cerebrovascular event than were those without diabetes. Those with newly diagnosed diabetes were 43% more likely to die and 18% more likely to have a significant adverse event than were those without diabetes, Dr. Tschoepe reported at the annual meeting of the European Association for the Study of Diabetes.

At the time of their coronary events, some level of glycemic dysregulation affected 68% of the women and 60% of the men in the study.

At admission, 30% of women and 23% of men had diabetes. Testing identified diabetes in an additional 20% of women and 15% of men. Another 18% of women and 23% of men had impaired glucose tolerance or impaired fasting glucose.

There was a "striking difference" in diabetes treatment between the groups at discharge, Dr. Tschoepe said, with 47% of women and 37% of men on some form of therapy. Oral treatment was prescribed for 27% of the women and 37% of the men, while 39% of the women and 27% of the men were discharged on insulin; both of these differences were significant. Exactly the same number of men and women were discharged on the combination of insulin and oral therapy (6.2%).

Men were more likely to be discharged on dietary treatment alone (42% vs. 39%), but this was not a significant difference. Dr. Tschoepe added.

Patients were enrolled in the trial within 24 hours of treatment and followed for 3 years. In addition to cardiovascular treatment, all patients underwent an oral glucose tolerance test as recommended in 2007 by the European Society of Cardiology and the European Association for the Study of Diabetes.

There were 706 women in the cohort. The women were older than the men, average age 71 and 64 years, respectively; were less likely to have a prior MI, 13% vs. 19%; had fewer prior percutaneous coronary interventions, 12% vs. 18%; had more hypertension, 80% vs. 69%; were less likely to smoke, 25% vs. 40%; and were more likely to have a known history of diabetes, 30% vs. 23%.

The mean blood glucose value at admission was significantly higher in women than in men, 137 mg/dL vs. 127 mg/dL. Women also had a significantly higher HbA_1c, 6.1% vs. 5.8%. STEMI and NSTEMI were equally distributed in men and women.

Almost all of the patients underwent a coronary angiogram (95% of women, 97% of men). One-, two-, and three-vessel disease were equally distributed in both genders. Cardiovascular drug therapy did not significantly differ at discharge, with the vast majority receiving aspirin, clopidogrel, beta-blockers and ACE inhibitors as appropriate with guideline recommendations.

The SWEETHEART registry is funded by Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, Sanofi, and Novartis. Dr. Tschoepe Tschoepe has received consultancy and speaker remuneration from Astra Zeneca, Bristol-Myers, Squibb, Servier, Sanofi, and Novartis.

BERLIN – Women who are diagnosed with diabetes at the time of an acute myocardial infarction are three times more likely to die over the next 3 years as are similar women without diabetes.

In contrast, men whose diabetes was diagnosed during their hospitalization for acute MI had twice the risk of death after 3 years compared with men without diabetes, based on the latest results of the SWEETHEART registry, a prospective study of 2,767 patients with ST- or non-ST-elevation myocardial infarction.

Michele G. Sullivan/IMNG Medical Media

The double-whammy of diabetes and coronary artery disease is "extraordinarily dangerous" for women, said Dr. Diethelm Tschoepe of the Heart and Diabetes Center, Bad Oeynhausen, Germany. Women with a new diagnosis of diabetes "have a much, much worse prognostic gradient" than do men with newly diagnosed diabetes, and men and women without diabetes.

Dr. Tschoepe said the findings suggest there is a large population of women with longstanding, undiagnosed diabetes that goes unrecognized until a cardiovascular event. "The vigilance of women and their treatment physicians seems to be insufficient" to detect their diabetes.

Additionally, testing for diabetes needs to occur in all patients who experience a cardiovascular event, despite the logistic difficulty this might present, Dr. Tschoepe said. "I am working in a place where endocrinologists, cardiac surgeons, and cardiologists work together, but it is still a tough fight to get every patient tested."

Among women in the study, the 3-year mortality rate was 30% for those with known diabetes and 30.5% for those with newly diagnosed diabetes – significantly higher than the rates for those without diabetes and those with impaired glucose regulation (11% and 13% respectively).

Among men, the mortality rate was highest among those with known diabetes (35%), followed by those with newly diagnosed disease (22%). Both groups had significantly higher mortality than that seen in those without diabetes and those with impaired glucose regulation (11% each).

In the overall multivariate adjusted model, patients with known diabetes were 77% more likely to die and 68% more likely to experience a major cardiovascular or cerebrovascular event than were those without diabetes. Those with newly diagnosed diabetes were 43% more likely to die and 18% more likely to have a significant adverse event than were those without diabetes, Dr. Tschoepe reported at the annual meeting of the European Association for the Study of Diabetes.

At the time of their coronary events, some level of glycemic dysregulation affected 68% of the women and 60% of the men in the study.

At admission, 30% of women and 23% of men had diabetes. Testing identified diabetes in an additional 20% of women and 15% of men. Another 18% of women and 23% of men had impaired glucose tolerance or impaired fasting glucose.

There was a "striking difference" in diabetes treatment between the groups at discharge, Dr. Tschoepe said, with 47% of women and 37% of men on some form of therapy. Oral treatment was prescribed for 27% of the women and 37% of the men, while 39% of the women and 27% of the men were discharged on insulin; both of these differences were significant. Exactly the same number of men and women were discharged on the combination of insulin and oral therapy (6.2%).

Men were more likely to be discharged on dietary treatment alone (42% vs. 39%), but this was not a significant difference. Dr. Tschoepe added.

Patients were enrolled in the trial within 24 hours of treatment and followed for 3 years. In addition to cardiovascular treatment, all patients underwent an oral glucose tolerance test as recommended in 2007 by the European Society of Cardiology and the European Association for the Study of Diabetes.

There were 706 women in the cohort. The women were older than the men, average age 71 and 64 years, respectively; were less likely to have a prior MI, 13% vs. 19%; had fewer prior percutaneous coronary interventions, 12% vs. 18%; had more hypertension, 80% vs. 69%; were less likely to smoke, 25% vs. 40%; and were more likely to have a known history of diabetes, 30% vs. 23%.

The mean blood glucose value at admission was significantly higher in women than in men, 137 mg/dL vs. 127 mg/dL. Women also had a significantly higher HbA_1c, 6.1% vs. 5.8%. STEMI and NSTEMI were equally distributed in men and women.

Almost all of the patients underwent a coronary angiogram (95% of women, 97% of men). One-, two-, and three-vessel disease were equally distributed in both genders. Cardiovascular drug therapy did not significantly differ at discharge, with the vast majority receiving aspirin, clopidogrel, beta-blockers and ACE inhibitors as appropriate with guideline recommendations.

The SWEETHEART registry is funded by Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, Sanofi, and Novartis. Dr. Tschoepe Tschoepe has received consultancy and speaker remuneration from Astra Zeneca, Bristol-Myers, Squibb, Servier, Sanofi, and Novartis.

BERLIN – Insulin degludec, an investigational insulin with a prolonged half-life and a reportedly flatter pharmacokinetic profile with fewer high and low levels, showed a modest hypoglycemic edge over insulin glargine in a 52-week head-to-head comparison in patients with type 2 diabetes.

While insulin degludec (IDeg) ran statistically even with insulin glargine for total hypoglycemic episodes and for severe hyperglycemic episodes, the IDeg formulation led to significantly fewer nocturnal hypoglycemic episodes, with a relative risk reduction of 36%. However, because all hypoglycemic episodes were infrequent, the results showed an absolute reduction average of about 0.3 nocturnal episodes per patient on glargine to about 0.2 episodes per patient on degludec, Dr. Bernard Zinman reported at the meeting.

Mitchel L. Zoler/IMNG Medical Media

"You need to treat four patients for a year to prevent one nocturnal episode. To me, that sounds like a good deal," said Dr. Zinman, director of the Centre for Diabetes at Mount Sinai Hospital in Toronto. In contrast, the study results also showed that 50 patients with type 2 diabetes would need IDeg treatment for a year to prevent one severe hypoglycemic episode, compared with glargine, he added.

"We want to encourage using insulin earlier in patients with type 2 diabetes, but many physicians are afraid of insulin because of [the associated risk of] hypoglycemia. I think that physicians will use degludec preferentially in patients at high risk for hypoglycemia," Dr. Zinman said in an interview. He included in this risk group younger patients with type 1 diabetes, patients with type 1 diabetes who take insulin as multiple-dose injections, patients maintained on a tight-control regimen, and patients with a history of hypoglycemia. The low numbers of hypoglycemia episodes seen in his results reflected selection of low-risk patients, he added. The results "underestimate the clinical value [of preventing hypoglycemia] because in routine clinical practice hypoglycemia is more of an issue" than it was in this trial.

An application to approve IDeg for treating patients with either type 1 or type 2 diabetes is pending before the Food and Drug Administration, and last July Novo Nordisk, the company developing the drug, said that it expected a FDA advisory committee to consider the application in November 2012.

The trial enrolled 1,030 patients with established type 2 diabetes inadequately controlled by metformin and possibly other oral drugs and no history of insulin treatment. The researchers randomized 773 patients to once-daily treatment with IDeg and 257 to a once daily regimen of insulin glargine, with the dosage titrated to achieve pre-breakfast plasma glucose of 3.9-4.9 mmol/L. The patients average 59 years old, their average body mass index was about 31 kg/m², their average hemoglobin A_1c was 8.2%, and they had type 2 diabetes for an average of about 9 years.

Throughout the 52-week study, average HbA_1c levels in the two treatment arms tracked together and, at 1 year, the two groups had virtually identical average levels of about 7.3%. Fasting plasma glucose also tracked at similar rates in both arms during the study but, at 1 year, the average level was 0.43 mmol/L lower in the degludec group, a statistically significant difference. The average daily insulin dosage received by patients in each of the two arms was also virtually identical.

The rate of all confirmed hypoglycemia episodes was 18% lower among the IDeg-treated patients, compared with the controls, but this difference did not reach statistical significance. Severe hypoglycemia episodes – defined as events where the patient required help – showed an 86% relative risk reduction, but because the event rates in both arms was small this difference was also not statistically significant.

An additional analysis also looked at the incidence of hypoglycemic episodes during the maintenance phase of treatment in the study, after the first 16 weeks. During maintenance, the two arms failed to show a significant difference in any measure of hypoglycemic episodes except for nocturnal events, which degludec treatment cut by 49% relative to the glargine group, a statistically significant difference.

Other than hypoglycemia the two insulin analogues showed similar safety profiles.

The study was sponsored by Novo Nordisk, the company developing IDeg. Dr. Zinman said that he has been an advisor to Novo Nordisk, Merck, Sanofi-Aventis, and Boehringer Ingelheim, and research funding from Novo Nordisk, Merck, and Boehringer Ingelheim.

BERLIN – Insulin degludec, an investigational insulin with a prolonged half-life and a reportedly flatter pharmacokinetic profile with fewer high and low levels, showed a modest hypoglycemic edge over insulin glargine in a 52-week head-to-head comparison in patients with type 2 diabetes.

While insulin degludec (IDeg) ran statistically even with insulin glargine for total hypoglycemic episodes and for severe hyperglycemic episodes, the IDeg formulation led to significantly fewer nocturnal hypoglycemic episodes, with a relative risk reduction of 36%. However, because all hypoglycemic episodes were infrequent, the results showed an absolute reduction average of about 0.3 nocturnal episodes per patient on glargine to about 0.2 episodes per patient on degludec, Dr. Bernard Zinman reported at the meeting.

Mitchel L. Zoler/IMNG Medical Media

"You need to treat four patients for a year to prevent one nocturnal episode. To me, that sounds like a good deal," said Dr. Zinman, director of the Centre for Diabetes at Mount Sinai Hospital in Toronto. In contrast, the study results also showed that 50 patients with type 2 diabetes would need IDeg treatment for a year to prevent one severe hypoglycemic episode, compared with glargine, he added.

"We want to encourage using insulin earlier in patients with type 2 diabetes, but many physicians are afraid of insulin because of [the associated risk of] hypoglycemia. I think that physicians will use degludec preferentially in patients at high risk for hypoglycemia," Dr. Zinman said in an interview. He included in this risk group younger patients with type 1 diabetes, patients with type 1 diabetes who take insulin as multiple-dose injections, patients maintained on a tight-control regimen, and patients with a history of hypoglycemia. The low numbers of hypoglycemia episodes seen in his results reflected selection of low-risk patients, he added. The results "underestimate the clinical value [of preventing hypoglycemia] because in routine clinical practice hypoglycemia is more of an issue" than it was in this trial.

An application to approve IDeg for treating patients with either type 1 or type 2 diabetes is pending before the Food and Drug Administration, and last July Novo Nordisk, the company developing the drug, said that it expected a FDA advisory committee to consider the application in November 2012.

The trial enrolled 1,030 patients with established type 2 diabetes inadequately controlled by metformin and possibly other oral drugs and no history of insulin treatment. The researchers randomized 773 patients to once-daily treatment with IDeg and 257 to a once daily regimen of insulin glargine, with the dosage titrated to achieve pre-breakfast plasma glucose of 3.9-4.9 mmol/L. The patients average 59 years old, their average body mass index was about 31 kg/m², their average hemoglobin A_1c was 8.2%, and they had type 2 diabetes for an average of about 9 years.

Throughout the 52-week study, average HbA_1c levels in the two treatment arms tracked together and, at 1 year, the two groups had virtually identical average levels of about 7.3%. Fasting plasma glucose also tracked at similar rates in both arms during the study but, at 1 year, the average level was 0.43 mmol/L lower in the degludec group, a statistically significant difference. The average daily insulin dosage received by patients in each of the two arms was also virtually identical.

The rate of all confirmed hypoglycemia episodes was 18% lower among the IDeg-treated patients, compared with the controls, but this difference did not reach statistical significance. Severe hypoglycemia episodes – defined as events where the patient required help – showed an 86% relative risk reduction, but because the event rates in both arms was small this difference was also not statistically significant.

An additional analysis also looked at the incidence of hypoglycemic episodes during the maintenance phase of treatment in the study, after the first 16 weeks. During maintenance, the two arms failed to show a significant difference in any measure of hypoglycemic episodes except for nocturnal events, which degludec treatment cut by 49% relative to the glargine group, a statistically significant difference.

Other than hypoglycemia the two insulin analogues showed similar safety profiles.

The study was sponsored by Novo Nordisk, the company developing IDeg. Dr. Zinman said that he has been an advisor to Novo Nordisk, Merck, Sanofi-Aventis, and Boehringer Ingelheim, and research funding from Novo Nordisk, Merck, and Boehringer Ingelheim.

BERLIN – Insulin degludec, an investigational insulin with a prolonged half-life and a reportedly flatter pharmacokinetic profile with fewer high and low levels, showed a modest hypoglycemic edge over insulin glargine in a 52-week head-to-head comparison in patients with type 2 diabetes.

While insulin degludec (IDeg) ran statistically even with insulin glargine for total hypoglycemic episodes and for severe hyperglycemic episodes, the IDeg formulation led to significantly fewer nocturnal hypoglycemic episodes, with a relative risk reduction of 36%. However, because all hypoglycemic episodes were infrequent, the results showed an absolute reduction average of about 0.3 nocturnal episodes per patient on glargine to about 0.2 episodes per patient on degludec, Dr. Bernard Zinman reported at the meeting.

Mitchel L. Zoler/IMNG Medical Media

"You need to treat four patients for a year to prevent one nocturnal episode. To me, that sounds like a good deal," said Dr. Zinman, director of the Centre for Diabetes at Mount Sinai Hospital in Toronto. In contrast, the study results also showed that 50 patients with type 2 diabetes would need IDeg treatment for a year to prevent one severe hypoglycemic episode, compared with glargine, he added.

"We want to encourage using insulin earlier in patients with type 2 diabetes, but many physicians are afraid of insulin because of [the associated risk of] hypoglycemia. I think that physicians will use degludec preferentially in patients at high risk for hypoglycemia," Dr. Zinman said in an interview. He included in this risk group younger patients with type 1 diabetes, patients with type 1 diabetes who take insulin as multiple-dose injections, patients maintained on a tight-control regimen, and patients with a history of hypoglycemia. The low numbers of hypoglycemia episodes seen in his results reflected selection of low-risk patients, he added. The results "underestimate the clinical value [of preventing hypoglycemia] because in routine clinical practice hypoglycemia is more of an issue" than it was in this trial.

An application to approve IDeg for treating patients with either type 1 or type 2 diabetes is pending before the Food and Drug Administration, and last July Novo Nordisk, the company developing the drug, said that it expected a FDA advisory committee to consider the application in November 2012.

The trial enrolled 1,030 patients with established type 2 diabetes inadequately controlled by metformin and possibly other oral drugs and no history of insulin treatment. The researchers randomized 773 patients to once-daily treatment with IDeg and 257 to a once daily regimen of insulin glargine, with the dosage titrated to achieve pre-breakfast plasma glucose of 3.9-4.9 mmol/L. The patients average 59 years old, their average body mass index was about 31 kg/m², their average hemoglobin A_1c was 8.2%, and they had type 2 diabetes for an average of about 9 years.

Throughout the 52-week study, average HbA_1c levels in the two treatment arms tracked together and, at 1 year, the two groups had virtually identical average levels of about 7.3%. Fasting plasma glucose also tracked at similar rates in both arms during the study but, at 1 year, the average level was 0.43 mmol/L lower in the degludec group, a statistically significant difference. The average daily insulin dosage received by patients in each of the two arms was also virtually identical.

The rate of all confirmed hypoglycemia episodes was 18% lower among the IDeg-treated patients, compared with the controls, but this difference did not reach statistical significance. Severe hypoglycemia episodes – defined as events where the patient required help – showed an 86% relative risk reduction, but because the event rates in both arms was small this difference was also not statistically significant.

An additional analysis also looked at the incidence of hypoglycemic episodes during the maintenance phase of treatment in the study, after the first 16 weeks. During maintenance, the two arms failed to show a significant difference in any measure of hypoglycemic episodes except for nocturnal events, which degludec treatment cut by 49% relative to the glargine group, a statistically significant difference.

Other than hypoglycemia the two insulin analogues showed similar safety profiles.

The study was sponsored by Novo Nordisk, the company developing IDeg. Dr. Zinman said that he has been an advisor to Novo Nordisk, Merck, Sanofi-Aventis, and Boehringer Ingelheim, and research funding from Novo Nordisk, Merck, and Boehringer Ingelheim.