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PHILADELPHIA – Daily insulin glargine for patients with diabetes appears to have no effect on the occurrence of breast, prostate, colorectal, lung, pancreatic, or any other type of cancer.
Studies of three large administrative databases agree: Compared with other forms of insulin, glargine (Lantus) confers absolutely no increase in the risk of any of these cancers.
Since 2009, when four articles simultaneously raised the specter of a glargine-cancer connection, researchers, physicians, and patients have struggled with concerns that the compound could impart its own health risks. These questions must be answered as definitively as possible, Peter Boyle, Ph.D., said at the annual scientific sessions of the American Diabetes Association.
Not doing so could have devastating consequences.
"None of our results support this hypothesis that short-term use of glargine is associated with any form of cancer."
"The big worry is that by 2030, we will have more than 500 million people living with diabetes. Many of them will require insulin. Without it, they will die unnecessarily prematurely. If we don’t take a more regulated approach [into researching the cancer association], and use a lot of common sense while doing so, there could be a shortage of a drug that we absolutely need to treat this very common disease."
Dr. Boyle is the primary investigator of the Northern European Study of Insulin and Cancer, the largest-yet registry study of glargine and NPH insulin, and their relation to cancer. His study, combined with the two others presented at the same session, comprised more than 615,000 patients, with well over 1.5 million patient/years of follow-up data.
Dr. Boyle examined the glargine-cancer connection in 447,821 patients with diabetes who used daily insulin. This study had the longest follow-up of the trio – 3 years for patients using glargine and 3.5 years for those using other types of insulin.
It was conducted in five countries: Scotland, Norway, Sweden, Denmark, and Finland. This study also had the longest follow-up time – 3 years for patients using glargine and 3.5 years for those using other insulins. It compared cancer incidence in two groups: patients taking glargine or other insulin for the first time, and patients who switched from another insulin to glargine.
Over the study period, 17,800 new cases of cancer developed, said Dr. Boyle, president of the International Prevention Research Institute, Lyon, France. "In none of the individual cancers, nor in the overall analysis, did we see any evidence at all of an increased risk of cancer associated with the use of glargine, compared with other forms of insulin. Even though we saw some inconsistencies [in cancer incidence] across the different countries, none of the risk analyses came anywhere close to meeting statistical significance."
The overall risk for colorectal cancer in patients taking glargine, compared with other forms of insulin, was 0.86 – a finding consistent over all the study centers.
Findings for prostate cancer were less consistent, but this was most likely because some of the countries in the study conduct many prostate cancer screenings, "while in other countries, PSA testing is virtually verboten," Dr. Boyle said. Nevertheless, the overall risk for prostate cancer in glargine vs. other insulins was 1.11 – still not statistically significant.
Breast cancers showed a similar finding, with an overall relative risk of 1.12 for glargine, compared with other forms of insulin.
A predefined exploratory analysis examined risks associated with lung and pancreatic cancer. For glargine vs. other forms of insulin, the overall relative risk for lung cancer was 0.97; for pancreatic cancer, the relative risk was 0.99.
"There is just nothing there at all," Dr. Boyle said.
"The big worry is that by 2030, we will have more than 500 million people living with diabetes."
The second portion of the analysis examined cancer risk in light of exposure length. Breast cancer was the only type that showed any signal, and that was a confusing one, he said. While in most countries, the risk declined with time, "In the Scottish data, increasing use was associated with increasing hazard. This really is terribly inconsistent, and we need to look into it in greater detail."
However, he said, the contradictory finding perfectly illustrates the trouble with using large surveillance databases to make any kind of prediction about drug/adverse event associations.
"Quite frankly, these administrative databases were not designed for epidemiologic studies. We’ve got to do our best to come up with real findings that mean something rather than just torturing the data until something shows up. Critical bits of information are missing from these pictures. We don’t know why a patient might change from one therapy to another, for instance. There are a lot of questions like that, and these are the first things that a clinician needs to know."
Dr. Laurel Habel, a senior researcher at Kaiser Permanente, presented similar findings of no increased cancer risk from glargine exposure. Her study was based on Kaiser’s northern and southern California claims and coding databases. The study group comprised 115,000 patients with diabetes – 100,000 took NPH insulin, 27,000 took glargine, and 12,000 took both. The median follow-up time was 2.3 years for glargine and 3.6 years for NPH.
"We found no evidence of increased prostate or colorectal cancer for glargine users, whether they were new users or whether they had switched to it," she said.
In a time exposure analysis of breast cancer risk, those who had been on glargine at baseline had a "suggestion of a very modest increase in risk, of 1.6." after 24 months. Curiously, she said, there was no risk increase for patients who had been on glargine for at least 2 years after switching from another insulin.
"We can’t think of any biological reason why we would only see this in the new users, so it might be a case of confounding," she said. "None of our results support this hypothesis that short-term use of glargine is associated with any form of cancer."
For prostate and colorectal cancers, there were no significant associations in any of the analyses, or in the time-dependent comparisons
Dr. Til Stürmer of the University of North Carolina at Chapel Hill presented the smallest study, but had results entirely consistent with those of his colleagues. Again, the comparison group of 52,553 patients was drawn from a large healthcare database. Median follow-up was 1.5 years for both the glargine and other insulin groups.
In looking at the relative risks of breast, prostate, colon. and all cancer, Dr. Stürmer found no significant associations with either new glargine users or those who switched medications. Compared with other insulins, glargine had a relative risk of 1.1 for breast cancer, 1.2 for prostate cancer, 0.9 for colon cancer, and 1.1 for all forms of cancer.
"In a subgroup looking at breast cancer stratified by time [0-6 months, 6-12 months, 12-24 months and longer than 24 months] the hazard ratios jumped around the null, but we only had 14 cancers in 4,000 person/years," he added.
All of the registry studies received support from Sanofi. Other than this funding, none of the presenters had any financial declarations relevant to their studies.
On June 6, 2009, four articles about a possible link between the drug and incident cancer were simultaneously published. Although the authors were somewhat temperate in their conclusions, the lay press took this up with the screaming headline, "Insulin Treatment Causes Cancer!"
The public deemed insulin harmful to people with diabetes. And immediately, database scrutiny attempted to address this question.
 |
|
Researchers want to know what we can learn about the usefulness of pharmacosurveillance databases for safety signals. And clinicians want to know if it’s safe to prescribe glargine.
If there is one take-home message from this group of studies, presented at the American Diabetes Association’s 2012 meeting – it’s "Yes. Glargine is safe and the benefits clearly outweigh the risks."
The other question is not so easy to answer.
Administrative databases can only tell us so much about patients and their experiences. Confounding is a crucial factor that often jeopardizes theses analyses. Missing data are the worst problem here. For instance, smoking status is typically missing in registry data. And yet smoking is common in diabetes and a huge risk factor for cancer. But missing smoking data do not equate to nonsmoking status. You can’t control for confounders that aren’t even measured.
Nor do these databases tell us much about exposure. Exposure time is easy enough to see in patients new to glargine. But we know nothing about prior exposure in those who switched to glargine. To accurately assess outcomes, we need to follow exposure with enough time to allow disease to develop in accordance with its natural history – which brings up another problem. Cancer has a very long latency. Its development can precede an exposure by years, creating the illusion that there is a relationship – when it was really present subclinically all along.
And finally – association does not imply causation. An association is just that – an association – until proven otherwise.
The punchline is this: It’s really hard to do these studies correctly. Cavalier publications of this or that exposure and risk are irresponsible and even harmful – particularly in the case of the glargine-cancer connection.
Insulin is lifesaving. We need it to treat diabetes. And we don’t want to limit our treatment options by prematurely worrying about signals coming up in poorly constructed studies.
Dr. James Meigs is director of the Massachusetts General Hospital’s clinical disease management research unit, in Boston. These remarks are taken from his presentation on the clinical implications of the findings presented by Dr. Boyle, Dr. Habel, and Dr. Stürmer. He had no financial disclosures.
On June 6, 2009, four articles about a possible link between the drug and incident cancer were simultaneously published. Although the authors were somewhat temperate in their conclusions, the lay press took this up with the screaming headline, "Insulin Treatment Causes Cancer!"
The public deemed insulin harmful to people with diabetes. And immediately, database scrutiny attempted to address this question.
|
|
Researchers want to know what we can learn about the usefulness of pharmacosurveillance databases for safety signals. And clinicians want to know if it’s safe to prescribe glargine.
If there is one take-home message from this group of studies, presented at the American Diabetes Association’s 2012 meeting – it’s "Yes. Glargine is safe and the benefits clearly outweigh the risks."
The other question is not so easy to answer.
Administrative databases can only tell us so much about patients and their experiences. Confounding is a crucial factor that often jeopardizes theses analyses. Missing data are the worst problem here. For instance, smoking status is typically missing in registry data. And yet smoking is common in diabetes and a huge risk factor for cancer. But missing smoking data do not equate to nonsmoking status. You can’t control for confounders that aren’t even measured.
Nor do these databases tell us much about exposure. Exposure time is easy enough to see in patients new to glargine. But we know nothing about prior exposure in those who switched to glargine. To accurately assess outcomes, we need to follow exposure with enough time to allow disease to develop in accordance with its natural history – which brings up another problem. Cancer has a very long latency. Its development can precede an exposure by years, creating the illusion that there is a relationship – when it was really present subclinically all along.
And finally – association does not imply causation. An association is just that – an association – until proven otherwise.
The punchline is this: It’s really hard to do these studies correctly. Cavalier publications of this or that exposure and risk are irresponsible and even harmful – particularly in the case of the glargine-cancer connection.
Insulin is lifesaving. We need it to treat diabetes. And we don’t want to limit our treatment options by prematurely worrying about signals coming up in poorly constructed studies.
Dr. James Meigs is director of the Massachusetts General Hospital’s clinical disease management research unit, in Boston. These remarks are taken from his presentation on the clinical implications of the findings presented by Dr. Boyle, Dr. Habel, and Dr. Stürmer. He had no financial disclosures.
On June 6, 2009, four articles about a possible link between the drug and incident cancer were simultaneously published. Although the authors were somewhat temperate in their conclusions, the lay press took this up with the screaming headline, "Insulin Treatment Causes Cancer!"
The public deemed insulin harmful to people with diabetes. And immediately, database scrutiny attempted to address this question.
|
|
Researchers want to know what we can learn about the usefulness of pharmacosurveillance databases for safety signals. And clinicians want to know if it’s safe to prescribe glargine.
If there is one take-home message from this group of studies, presented at the American Diabetes Association’s 2012 meeting – it’s "Yes. Glargine is safe and the benefits clearly outweigh the risks."
The other question is not so easy to answer.
Administrative databases can only tell us so much about patients and their experiences. Confounding is a crucial factor that often jeopardizes theses analyses. Missing data are the worst problem here. For instance, smoking status is typically missing in registry data. And yet smoking is common in diabetes and a huge risk factor for cancer. But missing smoking data do not equate to nonsmoking status. You can’t control for confounders that aren’t even measured.
Nor do these databases tell us much about exposure. Exposure time is easy enough to see in patients new to glargine. But we know nothing about prior exposure in those who switched to glargine. To accurately assess outcomes, we need to follow exposure with enough time to allow disease to develop in accordance with its natural history – which brings up another problem. Cancer has a very long latency. Its development can precede an exposure by years, creating the illusion that there is a relationship – when it was really present subclinically all along.
And finally – association does not imply causation. An association is just that – an association – until proven otherwise.
The punchline is this: It’s really hard to do these studies correctly. Cavalier publications of this or that exposure and risk are irresponsible and even harmful – particularly in the case of the glargine-cancer connection.
Insulin is lifesaving. We need it to treat diabetes. And we don’t want to limit our treatment options by prematurely worrying about signals coming up in poorly constructed studies.
Dr. James Meigs is director of the Massachusetts General Hospital’s clinical disease management research unit, in Boston. These remarks are taken from his presentation on the clinical implications of the findings presented by Dr. Boyle, Dr. Habel, and Dr. Stürmer. He had no financial disclosures.
PHILADELPHIA – Daily insulin glargine for patients with diabetes appears to have no effect on the occurrence of breast, prostate, colorectal, lung, pancreatic, or any other type of cancer.
Studies of three large administrative databases agree: Compared with other forms of insulin, glargine (Lantus) confers absolutely no increase in the risk of any of these cancers.
Since 2009, when four articles simultaneously raised the specter of a glargine-cancer connection, researchers, physicians, and patients have struggled with concerns that the compound could impart its own health risks. These questions must be answered as definitively as possible, Peter Boyle, Ph.D., said at the annual scientific sessions of the American Diabetes Association.
Not doing so could have devastating consequences.
"None of our results support this hypothesis that short-term use of glargine is associated with any form of cancer."
"The big worry is that by 2030, we will have more than 500 million people living with diabetes. Many of them will require insulin. Without it, they will die unnecessarily prematurely. If we don’t take a more regulated approach [into researching the cancer association], and use a lot of common sense while doing so, there could be a shortage of a drug that we absolutely need to treat this very common disease."
Dr. Boyle is the primary investigator of the Northern European Study of Insulin and Cancer, the largest-yet registry study of glargine and NPH insulin, and their relation to cancer. His study, combined with the two others presented at the same session, comprised more than 615,000 patients, with well over 1.5 million patient/years of follow-up data.
Dr. Boyle examined the glargine-cancer connection in 447,821 patients with diabetes who used daily insulin. This study had the longest follow-up of the trio – 3 years for patients using glargine and 3.5 years for those using other types of insulin.
It was conducted in five countries: Scotland, Norway, Sweden, Denmark, and Finland. This study also had the longest follow-up time – 3 years for patients using glargine and 3.5 years for those using other insulins. It compared cancer incidence in two groups: patients taking glargine or other insulin for the first time, and patients who switched from another insulin to glargine.
Over the study period, 17,800 new cases of cancer developed, said Dr. Boyle, president of the International Prevention Research Institute, Lyon, France. "In none of the individual cancers, nor in the overall analysis, did we see any evidence at all of an increased risk of cancer associated with the use of glargine, compared with other forms of insulin. Even though we saw some inconsistencies [in cancer incidence] across the different countries, none of the risk analyses came anywhere close to meeting statistical significance."
The overall risk for colorectal cancer in patients taking glargine, compared with other forms of insulin, was 0.86 – a finding consistent over all the study centers.
Findings for prostate cancer were less consistent, but this was most likely because some of the countries in the study conduct many prostate cancer screenings, "while in other countries, PSA testing is virtually verboten," Dr. Boyle said. Nevertheless, the overall risk for prostate cancer in glargine vs. other insulins was 1.11 – still not statistically significant.
Breast cancers showed a similar finding, with an overall relative risk of 1.12 for glargine, compared with other forms of insulin.
A predefined exploratory analysis examined risks associated with lung and pancreatic cancer. For glargine vs. other forms of insulin, the overall relative risk for lung cancer was 0.97; for pancreatic cancer, the relative risk was 0.99.
"There is just nothing there at all," Dr. Boyle said.
"The big worry is that by 2030, we will have more than 500 million people living with diabetes."
The second portion of the analysis examined cancer risk in light of exposure length. Breast cancer was the only type that showed any signal, and that was a confusing one, he said. While in most countries, the risk declined with time, "In the Scottish data, increasing use was associated with increasing hazard. This really is terribly inconsistent, and we need to look into it in greater detail."
However, he said, the contradictory finding perfectly illustrates the trouble with using large surveillance databases to make any kind of prediction about drug/adverse event associations.
"Quite frankly, these administrative databases were not designed for epidemiologic studies. We’ve got to do our best to come up with real findings that mean something rather than just torturing the data until something shows up. Critical bits of information are missing from these pictures. We don’t know why a patient might change from one therapy to another, for instance. There are a lot of questions like that, and these are the first things that a clinician needs to know."
Dr. Laurel Habel, a senior researcher at Kaiser Permanente, presented similar findings of no increased cancer risk from glargine exposure. Her study was based on Kaiser’s northern and southern California claims and coding databases. The study group comprised 115,000 patients with diabetes – 100,000 took NPH insulin, 27,000 took glargine, and 12,000 took both. The median follow-up time was 2.3 years for glargine and 3.6 years for NPH.
"We found no evidence of increased prostate or colorectal cancer for glargine users, whether they were new users or whether they had switched to it," she said.
In a time exposure analysis of breast cancer risk, those who had been on glargine at baseline had a "suggestion of a very modest increase in risk, of 1.6." after 24 months. Curiously, she said, there was no risk increase for patients who had been on glargine for at least 2 years after switching from another insulin.
"We can’t think of any biological reason why we would only see this in the new users, so it might be a case of confounding," she said. "None of our results support this hypothesis that short-term use of glargine is associated with any form of cancer."
For prostate and colorectal cancers, there were no significant associations in any of the analyses, or in the time-dependent comparisons
Dr. Til Stürmer of the University of North Carolina at Chapel Hill presented the smallest study, but had results entirely consistent with those of his colleagues. Again, the comparison group of 52,553 patients was drawn from a large healthcare database. Median follow-up was 1.5 years for both the glargine and other insulin groups.
In looking at the relative risks of breast, prostate, colon. and all cancer, Dr. Stürmer found no significant associations with either new glargine users or those who switched medications. Compared with other insulins, glargine had a relative risk of 1.1 for breast cancer, 1.2 for prostate cancer, 0.9 for colon cancer, and 1.1 for all forms of cancer.
"In a subgroup looking at breast cancer stratified by time [0-6 months, 6-12 months, 12-24 months and longer than 24 months] the hazard ratios jumped around the null, but we only had 14 cancers in 4,000 person/years," he added.
All of the registry studies received support from Sanofi. Other than this funding, none of the presenters had any financial declarations relevant to their studies.
PHILADELPHIA – Daily insulin glargine for patients with diabetes appears to have no effect on the occurrence of breast, prostate, colorectal, lung, pancreatic, or any other type of cancer.
Studies of three large administrative databases agree: Compared with other forms of insulin, glargine (Lantus) confers absolutely no increase in the risk of any of these cancers.
Since 2009, when four articles simultaneously raised the specter of a glargine-cancer connection, researchers, physicians, and patients have struggled with concerns that the compound could impart its own health risks. These questions must be answered as definitively as possible, Peter Boyle, Ph.D., said at the annual scientific sessions of the American Diabetes Association.
Not doing so could have devastating consequences.
"None of our results support this hypothesis that short-term use of glargine is associated with any form of cancer."
"The big worry is that by 2030, we will have more than 500 million people living with diabetes. Many of them will require insulin. Without it, they will die unnecessarily prematurely. If we don’t take a more regulated approach [into researching the cancer association], and use a lot of common sense while doing so, there could be a shortage of a drug that we absolutely need to treat this very common disease."
Dr. Boyle is the primary investigator of the Northern European Study of Insulin and Cancer, the largest-yet registry study of glargine and NPH insulin, and their relation to cancer. His study, combined with the two others presented at the same session, comprised more than 615,000 patients, with well over 1.5 million patient/years of follow-up data.
Dr. Boyle examined the glargine-cancer connection in 447,821 patients with diabetes who used daily insulin. This study had the longest follow-up of the trio – 3 years for patients using glargine and 3.5 years for those using other types of insulin.
It was conducted in five countries: Scotland, Norway, Sweden, Denmark, and Finland. This study also had the longest follow-up time – 3 years for patients using glargine and 3.5 years for those using other insulins. It compared cancer incidence in two groups: patients taking glargine or other insulin for the first time, and patients who switched from another insulin to glargine.
Over the study period, 17,800 new cases of cancer developed, said Dr. Boyle, president of the International Prevention Research Institute, Lyon, France. "In none of the individual cancers, nor in the overall analysis, did we see any evidence at all of an increased risk of cancer associated with the use of glargine, compared with other forms of insulin. Even though we saw some inconsistencies [in cancer incidence] across the different countries, none of the risk analyses came anywhere close to meeting statistical significance."
The overall risk for colorectal cancer in patients taking glargine, compared with other forms of insulin, was 0.86 – a finding consistent over all the study centers.
Findings for prostate cancer were less consistent, but this was most likely because some of the countries in the study conduct many prostate cancer screenings, "while in other countries, PSA testing is virtually verboten," Dr. Boyle said. Nevertheless, the overall risk for prostate cancer in glargine vs. other insulins was 1.11 – still not statistically significant.
Breast cancers showed a similar finding, with an overall relative risk of 1.12 for glargine, compared with other forms of insulin.
A predefined exploratory analysis examined risks associated with lung and pancreatic cancer. For glargine vs. other forms of insulin, the overall relative risk for lung cancer was 0.97; for pancreatic cancer, the relative risk was 0.99.
"There is just nothing there at all," Dr. Boyle said.
"The big worry is that by 2030, we will have more than 500 million people living with diabetes."
The second portion of the analysis examined cancer risk in light of exposure length. Breast cancer was the only type that showed any signal, and that was a confusing one, he said. While in most countries, the risk declined with time, "In the Scottish data, increasing use was associated with increasing hazard. This really is terribly inconsistent, and we need to look into it in greater detail."
However, he said, the contradictory finding perfectly illustrates the trouble with using large surveillance databases to make any kind of prediction about drug/adverse event associations.
"Quite frankly, these administrative databases were not designed for epidemiologic studies. We’ve got to do our best to come up with real findings that mean something rather than just torturing the data until something shows up. Critical bits of information are missing from these pictures. We don’t know why a patient might change from one therapy to another, for instance. There are a lot of questions like that, and these are the first things that a clinician needs to know."
Dr. Laurel Habel, a senior researcher at Kaiser Permanente, presented similar findings of no increased cancer risk from glargine exposure. Her study was based on Kaiser’s northern and southern California claims and coding databases. The study group comprised 115,000 patients with diabetes – 100,000 took NPH insulin, 27,000 took glargine, and 12,000 took both. The median follow-up time was 2.3 years for glargine and 3.6 years for NPH.
"We found no evidence of increased prostate or colorectal cancer for glargine users, whether they were new users or whether they had switched to it," she said.
In a time exposure analysis of breast cancer risk, those who had been on glargine at baseline had a "suggestion of a very modest increase in risk, of 1.6." after 24 months. Curiously, she said, there was no risk increase for patients who had been on glargine for at least 2 years after switching from another insulin.
"We can’t think of any biological reason why we would only see this in the new users, so it might be a case of confounding," she said. "None of our results support this hypothesis that short-term use of glargine is associated with any form of cancer."
For prostate and colorectal cancers, there were no significant associations in any of the analyses, or in the time-dependent comparisons
Dr. Til Stürmer of the University of North Carolina at Chapel Hill presented the smallest study, but had results entirely consistent with those of his colleagues. Again, the comparison group of 52,553 patients was drawn from a large healthcare database. Median follow-up was 1.5 years for both the glargine and other insulin groups.
In looking at the relative risks of breast, prostate, colon. and all cancer, Dr. Stürmer found no significant associations with either new glargine users or those who switched medications. Compared with other insulins, glargine had a relative risk of 1.1 for breast cancer, 1.2 for prostate cancer, 0.9 for colon cancer, and 1.1 for all forms of cancer.
"In a subgroup looking at breast cancer stratified by time [0-6 months, 6-12 months, 12-24 months and longer than 24 months] the hazard ratios jumped around the null, but we only had 14 cancers in 4,000 person/years," he added.
All of the registry studies received support from Sanofi. Other than this funding, none of the presenters had any financial declarations relevant to their studies.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN DIABETES ASSOCIATION
Major Finding: When comparing glargine to other insulins, the relative risks for breast, colorectal, and prostate cancer never exceeded 1.6, and none approached statistical significance.
Data Source: Data were drawn from three large heath care claims and coding databases.
Disclosures: All of the registry studies received support from Sanofi. Other than this funding, none of the presenters had any financial declarations relevant to their studies.