#311 “Ultralong”-acting insulin for diabetes: How long is long enough?
CLINICAL QUESTION
In patients with diabetes (type 1 or 2), how does the “ultralong”- acting insulin degludec compare to long-acting or NPH insulin?
BOTTOM LINE
In both type 1 and 2 diabetes, insulin degludec reduces the risk of severe hypoglycemia compared to insulin glargine [number needed to treat (NNT)=17-59]. The risk of symptomatic hypoglycemia is either similar, or at best lower with degludec (NNT=19-29), with no other differences in clinical outcomes or hemoglobin A1c.
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EVIDENCE
- Degludec versus glargine 100 units/mL:
- Five systematic reviews1-5 compared degludec to glargine in individuals with type 1 diabetes [4 randomized controlled trials (RCTs), 1477 patients] and type 2 diabetes (10-15 RCTs, 9619-16,328 patients) with follow-up 12 weeks to 2 years:
- Hemoglobin A1c: Differences not clinically significant (≤0.1%).1-5
- Hypoglycemia:
- Severe (requiring assistance) hypoglycemia: Most showed relative risk reduction (RRR) ~30%1,3,4 with degludec, whereas another found no statistically significant difference.5
- Symptomatic hypoglycemia: Range from no statistical difference1,4 to RRR 18%.2
- E.g., in blinded RCTs:6-8 NNT=17-59 for severe hypoglycemia and NNT=19-29 for overall hypoglycemia.
- No differences in severe adverse events, treatment discontinuation, death, cardiovascular events, or weight gain.
- Hypoglycemia:
- Hemoglobin A1c: Differences not clinically significant (≤0.1%).1-5
- Limitations:
- Some meta-analyses1,4 included RCTs with thrice-weekly degludec and mixed insulins. Symptomatic hypoglycemia would be statistically different without these RCTs;
- Review of type 1 diabetes excluded hypoglycemia outcomes from largest RCT;5
- All RCTs industry-funded and only 3 were blinded.6-8
- Five systematic reviews1-5 compared degludec to glargine in individuals with type 1 diabetes [4 randomized controlled trials (RCTs), 1477 patients] and type 2 diabetes (10-15 RCTs, 9619-16,328 patients) with follow-up 12 weeks to 2 years:
- Degludec versus glargine 300 units/mL (1 RCT, 924 patients): No difference in any outcome.9
- Degludec versus detemir:
- Type 1 diabetes (2 RCTs, 806 patients): No differences except in 1 RCT in 1 out of 5 nocturnal hypoglycemia outcomes.5
- Type 2 diabetes: No RCTs.3
- Degludec versus NPH insulin: No RCTs.1-5,10
- Insulin degludec’s longer half-life (24 hours versus glargine’s ~12) increases administration time flexibility,11 but takes 3-4 days to see the full effect of dose changes (versus glargine’s 1-2 days).
- Guidelines suggest degludec over detemir/glargine 100 units/mL to reduce hypoglycemia in both type 1 and 2 diabetes.11,12
- Detemir/glargine do not consistently reduce severe hypoglycemia versus NPH insulin, with similar efficacy.13
- Costs/15mL: Degludec $135, detemir $135, glargine (Basaglar®) $90, NPH $65.14
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