Cardiovascular safety and lower severe hypoglycaemia of insulin degludec versus insulin glargine U100 in patients with type 2 diabetes aged 65 years or older: Results from DEVOTE (DEVOTE 7)

Abstract

Aims The aim of this study was to describe the risks of cardiovascular (CV) events and severe hypoglycaemia with insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes (T2D) aged 65 years or older. Materials and methods A total of 7637 patients in the DEVOTE trial, a treat‐to‐target, randomized, double‐blind trial evaluating the CV safety of degludec vs glargine U100, were divided into three age groups (50‐64 years, n = 3682; 65‐74 years, n = 3136; ≥75 years, n = 819). Outcomes by overall age group and randomized treatment differences were analysed for major adverse cardiovascular events (MACE), all‐cause mortality, severe hypoglycaemia and serious adverse events (SAEs). Results Patients with increasing age had higher risks of CV death, all‐cause mortality and SAEs, and there were non‐significant trends towards higher risks of MACE and severe hypoglycaemia. Treatment effects on the risk of MACE, all‐cause mortality, severe hypoglycaemia and SAEs were consistent across age groups, based on the non‐significant interactions between treatment and age with regard to these outcomes. Conclusions There were higher risks of CV death, all‐cause mortality and SAEs, and trends towards higher risks of MACE and severe hypoglycaemia with increasing age after adjusting for baseline differences. The effects across age groups of degludec vs glargine U100 on MACE, all‐cause mortality and severe hypoglycaemia were comparable, suggesting that the risk of MACE, as well as all‐cause mortality, is similar and the risk of severe hypoglycaemia is lower with degludec regardless of age. Evidence is conclusive only until 74 years of age.

The Safety and Efficacy of Second-Generation Basal Insulin Analogues in Adults with Type 2 Diabetes at Risk of Hypoglycemia and Use in Other Special Populations: A Narrative Review

“…A number of meta-analyses [ 62 – 64 ], as well as one prospectively designed RCT [ 65 ], post-hoc analyses and RWE [ 42 , 43 , 66 , 67 ], have evaluated the risk of hypoglycemia with second-generation BI analogues in older people, as summarized in Table 1 .…”

“…Pratley et al undertook a post-hoc analysis of the DEVOTE (CV outcomes trial comparing IDeg with Gla-100) population to investigate the effect of increased age and major CV events (primary endpoint) and severe hypoglycemia (secondary endpoint) [ 67 ]. Randomized patients ( n = 7637; mean age 65 years) on either IDeg or Gla-100 were included in this analysis and divided into three age groups: 50–64 years ( n = 3682); 65–74 years ( n = 3136) and ≥ 75 years ( n = 819).…”

“…The most frequent serious AEs were cardiac disorders, which were reported in 19% of patients aged ≥ 75 years, 15.5% of those aged 50–64 years and 15% of subjects aged 50–64 years. The authors concluded that further data for the risk of hypoglycemia were warranted in older individuals ≥ 75 years [ 67 ].…”

“…Evidence to date demonstrates that second-generation BI analogues have comparable HbA1c control to first-generation BI analogues, but a lower association to hypoglycemia. This holds true across a wide range of patients: individuals with obesity, subjects with CVD and populations at risk of hypoglycemia, such as older adults, subjects with renal impairment and individuals with a long duration of diabetes or insulin use [ 11 , 35 , 42 , 43 , 62 – 67 , 69 ]. Less hypoglycemia associated with second-generation BI analogues may be particularly meaningful in some of these vulnerable populations by removing barriers to insulin initiation, improving adherence [ 71 ], potentially improving QoL [ 88 , 89 ] and reducing hypoglycemia-related healthcare resource utilization and associated costs [ 44 ].…”

Cardiovascular safety outcomes of once‐weekly GLP‐1 receptor agonists in people with type 2 diabetes

“…To date, there have been no head‐to‐head T2D CVOTs within any class of glucose‐lowering drugs, except insulin (insulin glargine vs insulin degludec) 36 and only one head‐to‐head T2D CVOT between two classes of drugs in this therapy area (linagliptin vs glimepiride) 37 . To inform pharmacists, data from the three QW GLP‐1 RA trials are presented here; however, any cross‐trial comparisons should always be interpreted with caution, as they may be confounded by multiple uncontrolled factors due to lack of consistency in overall trial design.…”