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#311 “Ultralong”-acting insulin for diabetes: How long is long enough?

In patients with diabetes (type 1 or 2), how does the “ultralong”- acting insulin degludec compare to long-acting or NPH insulin?

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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  • 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.
    • 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;
      • All RCTs industry-funded and only 3 were blinded.6-8
  • 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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  • Ricky D Turgeon BSc (Pharm) ACPR PharmD
  • Justin Weresch MD CCFP

1. Zhang XW, Zhang XL, Xu B, et al. Acta Diabetologica. 2018; 55:429-41.

2. Liu W, Yang X, Huang J. Int J Endocrinol. 2018; 2018:8726046.

3. Holmes RS, Crabtree E, McDonagh MS. Diabetes Obes Metab. 2019; 21:984-92.

4. Zhou W, Tao J, Zhou X, Chen H. Diabetes Ther. 2019; 10:835-52.

5. Hemmingsen B, Metzendorf MI, Richter B. Cochrane Database Syst Rev. 2021; 3:CD013498.

6. Lane W, Bailey TS, Gerety G, et al. JAMA. 2017; 318:33-44.

7. Marso SP, McGuire DK, Zinman B, et al. N Engl J Med. 2017; 377:723-32.

8. Wysham C, Bhargava A, Chaykin L, et al. JAMA. 2017; 318:45-56.

9. Rosenstock J, Cheng A, Ritzel R, et al. Diabetes Care. 2018; 41:2147-54.

10. Semlitsch T, Engler J, Siebenhofer A, et al. Cochrane Database Syst Rev. 2020; 11:CD005613.

11. McGibbon A, Adams L, Ingersoll K, et al. Can J Diabetes. 2018; 42:S80-S87.

12. Lipscombe L, Butalia S, Dagupta K, et al. Can J Diabetes. 2020; 44:575-91.

13. Allan GM, Virani AS. Tools for Practice #35 online publication. October 26, 2010 (updated January 29, 2018). Available at: Accessed March 14, 2022.

14. Alberta College of Family Physicians. 2020 Pricing Document. Available at: Accessed January 13, 2022.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.