All-Cause and Cause-Specific Mortality among Users of Basal Insulins NPH, Detemir, and Glargine

Abstract

BackgroundInsulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown.ObjectiveTo estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland.Methods23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006–2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years).Results2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30–0.50) for detemir, and 0.55 (95% CI, 0.44–0.69) for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54–0.93) among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses.ConclusionIn real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.

Comparative effectiveness and harms of long‐acting insulins for type 1 and type 2 diabetes: A systematic review and meta‐analysis

“…The total number of patients in the remaining fair‐quality trials was 2762, with 12‐52 weeks of treatment. We included 12 observational studies (eight with hypoglycaemia outcomes and four with cancer outcomes), of which one was poor quality …”

“…We found low‐strength evidence of no difference in the risk of any cancer or of breast cancer between detemir and glargine. Evidence on cancer mortality with glargine or detemir was insufficient to draw conclusions . Three retrospective cohort studies and a case‐control study (N = 240 101) evaluated the association of insulin exposure with a diagnosis of any cancer, and three cohort studies reported on the risk of breast cancer .…”

“…[49][50][51] The total number of patients in the remaining fairquality trials was 2762, with 12-52 weeks of treatment. We included 12 observational studies (eight with hypoglycaemia outcomes 40,[52][53][54][55][56][57][58] and four with cancer outcomes [59][60][61][62] ), of which one was poor quality. 52 There was low-strength evidence of no significant difference in glycaemic control between detemir and glargine based on seven trials.…”

“…Evidence on cancer mortality with glargine or detemir was insufficient to draw conclusions. 62 Three retrospective cohort studies and a case-control study (N = 240 101) evaluated the association of insulin exposure with a diagnosis of any cancer, [59][60][61]63 and three cohort studies reported on the risk of breast cancer. 60,63,64 (Appendix S1, Proportion of patients with type 2 diabetes that achieved HbA1c ≤ 7% with detemir versus glargine 3.3 | Glargine…”

Combined insulin detemir and liraglutide therapy in type 2 diabetic patients: a base for an alliance

“…и соавт. (2015) [60], исследований, использующих твердые (не суррогатные) конечные точки для оценки клинической эффективности и безопасности различных режимов инсулинотерапии у пациентов с СД2, чтобы подтвердить или исключить неблагоприятные сердечно-сосудистые эффекты дли-тельной терапии экзогенным инсулином, пока недоста-точно.…”