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To the Editor: We read with interest the article by Ching Sun et al1 on the relationship between diabetes therapy and cancer risk. We noted that there was no reference in the text to the long-acting insulins detemir and degludec, and we would like to add some relevant information.
With regard to detemir, a meta-analysis published in 2009 showed that patients treated with this insulin had a lower or similar rate of occurrence of a cancer compared with patients treated with neutral protamine Hagedorn insulin or insulin glargine.2 In addition, in a cohort study, no difference in cancer risk between insulin detemir users and nonusers was reported.3
Insulin detemir has a lower binding affinity for human insulin receptor isoform A (IR-A) relative to human insulin, and a much lower affinity for isoform B (IR-B). The binding affinity ratio of insulinlike growth factor-1 (IGF-1) receptor to insulin receptor for detemir is less than or equal to 1 relative to human insulin and displays a dissociation pattern from the insulin receptor that is similar to or faster than that of human insulin. Consequently, the relative mitogenic potency of detemir in cell types predominantly expressing either the IGF-1 receptor or the insulin receptor is low and corresponds to its IGF-1 receptor and insulin receptor affinities.4
Regarding insulin degludec, its affinity for both IR-A and IR-B, as well as for the IGF-1 receptor, has been found to be lower than human insulin. Its mitogenic response, in the absence of albumin, was reported to range from 4% to 14% relative to human insulin.5 Furthermore, in cellular assays, in which no albumin was added, the in vitro metabolic potency was determined to be in the range of 8% to 20%, resulting in a mitogenic-to-metabolic potency ratio of 1 or lower.5
It appears that insulins detemir and degludec have low mitogenic potential. However, additional studies are needed, especially with degludec, to further determine long-term safety.
- Ching Sun GE, Kashyap SR, Nasr C. Diabetes therapy and cancer risk: where do we stand when treating patients? Cleve Clin J Med 2014; 81:620–628.
- Dejgaard A, Lynggaard H, Råstam J, Krogsgaard Thomsen M. No evidence of increased risk of malignancies in patients with diabetes treated with insulin detemir: a meta-analysis. Diabetologia 2009; 52:2507–2512.
- Fagot JP, Blotière PO, Ricordeau P, Weill A, Alla F, Allemand H. Does insulin glargine increase the risk of cancer compared with other basal insulins? A French nationwide cohort study based on national administrative databases. Diabetes Care 2013; 36:294–301.
- Hansen BF, Glendorf T, Hegelund AC, et al. Molecular characterization of long-acting insulin analogues in comparison with human insulin, IGF-1 and insulin X10. PLoS One 2012; 7:e34274.
- Nishimura E, Sørensen AR, Hansen BF, et al. Insulin degludec: a new ultra-long, basal insulin designed to maintain full metabolic effect while minimizing mitogenic potential. Diabetologia 2010; 53:S388–S389.
To the Editor: We read with interest the article by Ching Sun et al1 on the relationship between diabetes therapy and cancer risk. We noted that there was no reference in the text to the long-acting insulins detemir and degludec, and we would like to add some relevant information.
With regard to detemir, a meta-analysis published in 2009 showed that patients treated with this insulin had a lower or similar rate of occurrence of a cancer compared with patients treated with neutral protamine Hagedorn insulin or insulin glargine.2 In addition, in a cohort study, no difference in cancer risk between insulin detemir users and nonusers was reported.3
Insulin detemir has a lower binding affinity for human insulin receptor isoform A (IR-A) relative to human insulin, and a much lower affinity for isoform B (IR-B). The binding affinity ratio of insulinlike growth factor-1 (IGF-1) receptor to insulin receptor for detemir is less than or equal to 1 relative to human insulin and displays a dissociation pattern from the insulin receptor that is similar to or faster than that of human insulin. Consequently, the relative mitogenic potency of detemir in cell types predominantly expressing either the IGF-1 receptor or the insulin receptor is low and corresponds to its IGF-1 receptor and insulin receptor affinities.4
Regarding insulin degludec, its affinity for both IR-A and IR-B, as well as for the IGF-1 receptor, has been found to be lower than human insulin. Its mitogenic response, in the absence of albumin, was reported to range from 4% to 14% relative to human insulin.5 Furthermore, in cellular assays, in which no albumin was added, the in vitro metabolic potency was determined to be in the range of 8% to 20%, resulting in a mitogenic-to-metabolic potency ratio of 1 or lower.5
It appears that insulins detemir and degludec have low mitogenic potential. However, additional studies are needed, especially with degludec, to further determine long-term safety.
To the Editor: We read with interest the article by Ching Sun et al1 on the relationship between diabetes therapy and cancer risk. We noted that there was no reference in the text to the long-acting insulins detemir and degludec, and we would like to add some relevant information.
With regard to detemir, a meta-analysis published in 2009 showed that patients treated with this insulin had a lower or similar rate of occurrence of a cancer compared with patients treated with neutral protamine Hagedorn insulin or insulin glargine.2 In addition, in a cohort study, no difference in cancer risk between insulin detemir users and nonusers was reported.3
Insulin detemir has a lower binding affinity for human insulin receptor isoform A (IR-A) relative to human insulin, and a much lower affinity for isoform B (IR-B). The binding affinity ratio of insulinlike growth factor-1 (IGF-1) receptor to insulin receptor for detemir is less than or equal to 1 relative to human insulin and displays a dissociation pattern from the insulin receptor that is similar to or faster than that of human insulin. Consequently, the relative mitogenic potency of detemir in cell types predominantly expressing either the IGF-1 receptor or the insulin receptor is low and corresponds to its IGF-1 receptor and insulin receptor affinities.4
Regarding insulin degludec, its affinity for both IR-A and IR-B, as well as for the IGF-1 receptor, has been found to be lower than human insulin. Its mitogenic response, in the absence of albumin, was reported to range from 4% to 14% relative to human insulin.5 Furthermore, in cellular assays, in which no albumin was added, the in vitro metabolic potency was determined to be in the range of 8% to 20%, resulting in a mitogenic-to-metabolic potency ratio of 1 or lower.5
It appears that insulins detemir and degludec have low mitogenic potential. However, additional studies are needed, especially with degludec, to further determine long-term safety.
- Ching Sun GE, Kashyap SR, Nasr C. Diabetes therapy and cancer risk: where do we stand when treating patients? Cleve Clin J Med 2014; 81:620–628.
- Dejgaard A, Lynggaard H, Råstam J, Krogsgaard Thomsen M. No evidence of increased risk of malignancies in patients with diabetes treated with insulin detemir: a meta-analysis. Diabetologia 2009; 52:2507–2512.
- Fagot JP, Blotière PO, Ricordeau P, Weill A, Alla F, Allemand H. Does insulin glargine increase the risk of cancer compared with other basal insulins? A French nationwide cohort study based on national administrative databases. Diabetes Care 2013; 36:294–301.
- Hansen BF, Glendorf T, Hegelund AC, et al. Molecular characterization of long-acting insulin analogues in comparison with human insulin, IGF-1 and insulin X10. PLoS One 2012; 7:e34274.
- Nishimura E, Sørensen AR, Hansen BF, et al. Insulin degludec: a new ultra-long, basal insulin designed to maintain full metabolic effect while minimizing mitogenic potential. Diabetologia 2010; 53:S388–S389.
- Ching Sun GE, Kashyap SR, Nasr C. Diabetes therapy and cancer risk: where do we stand when treating patients? Cleve Clin J Med 2014; 81:620–628.
- Dejgaard A, Lynggaard H, Råstam J, Krogsgaard Thomsen M. No evidence of increased risk of malignancies in patients with diabetes treated with insulin detemir: a meta-analysis. Diabetologia 2009; 52:2507–2512.
- Fagot JP, Blotière PO, Ricordeau P, Weill A, Alla F, Allemand H. Does insulin glargine increase the risk of cancer compared with other basal insulins? A French nationwide cohort study based on national administrative databases. Diabetes Care 2013; 36:294–301.
- Hansen BF, Glendorf T, Hegelund AC, et al. Molecular characterization of long-acting insulin analogues in comparison with human insulin, IGF-1 and insulin X10. PLoS One 2012; 7:e34274.
- Nishimura E, Sørensen AR, Hansen BF, et al. Insulin degludec: a new ultra-long, basal insulin designed to maintain full metabolic effect while minimizing mitogenic potential. Diabetologia 2010; 53:S388–S389.