Is the risk of hypoglycemia lower with insulin degludec than with insulin glargine in adults with type 2 diabetes?

Although the risk of overall symptomatic hypoglycemia was significantly lower with insulin degludec (Tresiba) than with insulin glargine (Lantus) in adults with type 2 diabetes, there was no significant difference in the risk of severe hypoglycemia (requiring third-party assistance). Similarly, past studies have found no difference in the risk of severe hypoglycemia between insulin glargine and NPH insulin. Clinicians should take into account the significantly lower cost of NPH insulin compared with insulin degludec and insulin glargine for their patients with type 2 diabetes. Additionally, the ACCORD study (NEJM 2008;358:2545-59) was stopped prematurely because of an increased risk of all-cause mortality with tight control (Hb A1c < 7.0 - 7.5) in type 2 diabetics. Another article in the same journal found a significantly lower risk of severe hypoglycemia with insulin degludec compared with insulin glargine in adults with type 1 diabetes. (LOE = 1b)

Wysham C, Bhargava A, Chaykin L, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 2 diabetes. The SWITCH 2 randomized clinical trial. JAMA 2017;318(1):45-56.  [PMID:28672317]

Randomized controlled trial (double-blinded)

Industry

Concealed

Outpatient (any)

Concerns regarding the risk of hypoglycemia are paramount in choosing therapy for adults with type 2 diabetes. These investigators identified adults (N = 721), 18 years or older, with type 2 diabetes for at least 26 weeks, a current Hb A1c level of 9.5% or lower, body mass index of 45 or lower, and using insulin with or without oral agents. Patients randomly received assignment (concealed allocation) to treatment with once-daily insulin degludec or insulin glargine U100 for 32 weeks followed by a cross over to the opposite treatment group for an additional 32 weeks, plus 1 additional week of follow-up. Each 32-week period consisted of a 16-week titration period to obtain stable glycemic control and a 16-week maintenance period to compare differences in hypoglycemia rates. Patients, clinicians, and outcome assessors remained masked to treatment group assignment. Complete follow-up occurred for 80.4% of patients at 65 weeks. Using intention-to-treat analysis, the rate of overall symptomatic hypoglycemia during the maintenance period was significantly lower with insulin degludec compared with insulin glargine U100 (185.6 vs 265.4 episodes per 100 patient-years of exposure, respectively). However, the rates of severe hypoglycemia during the maintenance period were similar in both treatment groups. The mean Hb A1c level at the end of treatment was 7.08% with insulin degludec and 7.11% with insulin glargine U100.