STATE OF THE ART PAPER
 
KEYWORDS
TOPICS
ABSTRACT
Pregestational diabetes is described when a woman with diabetes before the onset of pregnancy becomes pregnant and consequently she is vulnerable to higher risk for adverse outcomes in the embryo/foetus. Strict glycaemic control, with minimal glucose variability, starting from before conception and maintained throughout pregnancy decreases significantly adverse foetal and maternal outcomes; maternal hypoglycaemic episodes are the major barrier in achieving this goal. Insulin degludec is an ultralong-acting analogue, which has half-life of over 25 h and full duration of effect of more than 42 h, reaching a steady-state serum concentration after 2–3 days of its administration. It promotes flat, steady, peakless and predictable insulin concentrations, with minor intra-individual and inter-individual variability. It also exerts a low mitogenic/metabolic potency ratio. This review examines thoroughly all current evidence of the administration of insulin degludec in pregestational diabetes as well as its future role in this population.
 
REFERENCES (47)
1.
Papaetis GS, Papakyriakou P, Panagiotou TN. Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns. Arch Med Sci 2015; 11: 463-82.
 
2.
Papaetis G. SGLT2 inhibitors and diabetic kidney disease: targeting multiple and interrelated signaling pathways for renal protection. Curr Mol Pharmacol 2023; doi: 10.2174/0118761429261105231011101200.
 
3.
Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 2022; 183: 109119.
 
4.
Papaetis GS. SGLT2 inhibitors, intrarenal hypoxia and the diabetic kidney: insights into pathophysiological concepts and current evidence. Arch Med Sci Atheroscler Dis 2023; 8: 155-68.
 
5.
Britton LE, Hussey JM, Berry DC, Crandell JL, Brooks JL, Bryant AG. Contraceptive use among women with prediabetes and diabetes in a US national sample. J Midwifery Womens Health 2019; 64: 36-45.
 
6.
Blum AK. Insulin use in pregnancy: an update. Diabetes Spectr 2016; 29: 92-7.
 
7.
Ray JG, Vermeulen MJ, Meier C, Wyatt PR. Risk of congenital anomalies detected during antenatal serum screening in women with pregestational diabetes. Q J Med 2004; 97: 651-3.
 
8.
HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, Dyer AR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358: 1991-2002.
 
9.
Farrar D, Tuffnell DJ, West J, West HM. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes. Cochrane Database Syst Rev 2016; 6: CD005542.
 
10.
Sugrue R, Zera C. Pregestational diabetes in pregnancy. Obstet Gynecol Clin North Am 2018; 45: 315-31.
 
11.
Jethwani P, Saboo B, Jethwani L, et al. Use of insulin glargine during pregnancy: a review. Diabetes Metab Syndr 2021; 15: 379-84.
 
12.
Mathiesen ER, Hod M, Ivanisevic M, et al. Maternal efficacy and safety outcomes in a randomized, controlled trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1diabetes. Diabetes Care 2012; 35: 2012-7.
 
13.
Mathiesen ER, Ali N, Alibegovic AC, et al. Risk of major congenital malformations or perinatal or neonatal death with insulin detemir versus other basal insulins in pregnant women with preexisting diabetes: the real-world EVOLVE study. Diabetes Care 2021; 44: 2069-77.
 
14.
Di Cianni G, Torlone E, Lencioni C, et al. Perinatal outcomes associated with the use of glargine during pregnancy. Diabet Med 2008; 25: 993-6.
 
15.
Pantalone KM, Faiman C, Olansky L. Insulin glargine use during pregnancy. Endocr Pract 2011; 17: 448-55.
 
16.
Lepercq J, Lin J, Hall GC, et al. Meta-analysis of maternal and neonatal outcomes associated with the use of insulin glargine versus NPH insulin during pregnancy. Obstet Gynecol Int 2012; 2012: 649070.
 
17.
Devries JH, Nattrass M, Pieber TR. Refining basal insulin therapy: what have we learned in the age of analogues? Diabetes Metab Res Rev 2007; 23: 441-54.
 
18.
Kalra S, Gupta Y. Clinical use of insulin degludec: practical experience and pragmatic suggestions. N Am J Med Sci 2015; 7: 81-5.
 
19.
Russell-Jones D, Gall MA, Niemeyer M, et al. Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: a meta-analysis of seven clinical trials. Nutr Metab Cardiovasc Dis 2015; 25: 898-905.
 
20.
Marso SP, McGuire DK, Zinman B, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes N Engl J Med 2017; 377: 723-32.
 
21.
Jonassen I, Havelund S, Hoeg-Jensen T, Steensgaard DB, Wahlund PO, Ribel U. Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin. Pharm Res 2012; 29: 2104-14.
 
22.
Gough SC, Harris S, Woo V, Davies M. Insulin degludec: overview of a novel ultra long-acting basal insulin. Diabetes Obes Metab 2013; 15: 301-9.
 
23.
Kalra S, Baruah MP, Niazi AK. Degludec: a novel basal insulin. Recent Pat Endocr Metab Immune Drug Discov 2012; 6: 18-23.
 
24.
Haahr H, Heise T. A review of the pharmacological properties of insulin degludec and their clinical relevance. Clin Pharmacokinet 2014; 53: 787-800.
 
25.
European Medicines Agency (EMA). London: Committee for Medicinal Products for Human Use, 2013. Available from: http://www.ema.europa.eu/docs/... Accessed March 30, 2017.
 
26.
Milluzzo A, Tumminia A, Scalisi NM, Frittitta L, Vigneri R, Sciacca L. Insulin degludec in the first trimester of pregnancy: Report of two cases. J Diabetes Investig 2017; 9: 629-31.
 
27.
Formoso G, Ginestra F, Di Dalmazi G, Consoli A. Empagliflozin, metformin and insulin degludec, during pregnancy: a case report. Acta Diabetol 2018; 55: 759-61.
 
28.
Hiranput S, Ahmed SH, Macaulay D, Azmi S. Successful outcomes with insulin degludec in pregnancy: a case series. Diabetes Ther 2019; 10: 283-9.
 
29.
Bonora BM, Avogaro A, Fadini GP. Exposure to insulin degludec during pregnancy: report of a small series and review of the literature. J Endocrinol Invest 2019; 42: 345-9.
 
30.
Roman-Gonzalez A, Builes-Barrera CA, Aristizabal Baron A. Exposure to degludec during pregnancy: a case report. Cureus 2019; 11: e5158.
 
31.
Sprio E, Lucotti P, Iadarola C, Bellingeri C, Beneventi F, Lovati E. Use of insulin degludec in pregnancy: two case reports and a literature review. Endocr Metab Sci 2020; 1: 100064.
 
32.
Keller MF, Vestgaard M, Damm P, Mathiesen ER, Ringholm L. Treatment with the long-acting insulin analog degludec during pregnancy in women with type 1 diabetes: an observational study of 22 cases. Diabetes Res Clin Pract 2019; 152: 58-64.
 
33.
Martínez-Montoro JI, Hernández-García C, Picón-César MJ, et al. Assessment of materno-fetal complications in pregnant women with type 1 diabetes exposed to insulin degludec. Endocrine Abstracts 2019; 63: P622.
 
34.
Ringholm L, Do NC, Damm P, Mathiesen ER. Pregnancy outcomes in women with type 1 diabetes using insulin degludec. Acta Diabetol 2022; 59: 721-7.
 
35.
Mathiesen ER, Alibegovic AC, Corcoy R, et al. Insulin degludec versus insulin detemir, both in combination with insulin aspart, in the treatment of pregnant women with type 1 diabetes (EXPECT): an open label, multinational, randomised, controlled, non-inferiority trial. Lancet Diabetes Endocrinol 2023; 11: 86-95.
 
36.
Mathiesen E, Hod M, Jia T, Kalyanam B, Kar S, Damm P. Insulin degludec cord blood level and neonatal hypoglycaemia in pregnant women with type 1 diabetes in the EXPECT study. Diabetes Res Clin Pract 2023; 197S: 110552.
 
38.
Raets L, Ingelbrecht A, Benhalima K. Management of type 2 diabetes in pregnancy: a narrative review. Front Endocrinol (Lausanne) 2023; 14: 1193271.
 
39.
Henao-Carrillo DC, Muñoz OM, Gómez AM, et al. Reduction of glycemic variability with Degludec insulin in patients with unstable diabetes. J Clin Transl Endocrinol 2018; 12: 8-12.
 
40.
Siegmund T, Tentolouris N, Knudsen ST, et al. A European, multicentre, retrospective, non-interventional study (EU-TREAT) of the effectiveness of insulin degludec after switching basal insulin in a population with type 1 or type 2 diabetes. Diabetes Obes Metab 2018; 20: 689-97.
 
41.
Haldrup S, Lapolla A, Gundgaard J, Wolden ML. Cost-effectiveness of switching to insulin degludec from other basal insulins in real-world clinical practice in Italy. J Med Econ 2020; 23: 271-9.
 
42.
Oya J, Nakagami T, Hasegawa Y, Katamine A, Kondo Y, Babazono T. Comparative clinical outcomes of insulin degludec and insulin glargine 300 U/mL after switching from other basal insulins in real-world patients with type 1 and type 2 diabetes. J Diabetes Investig 2021; 12: 1983-91.
 
43.
Goldenberg RM, Aroda VR, Billings LK, et al. Effect of insulin degludec versus insulin glargine U100 on time in range: SWITCH PRO, a crossover study of basal insulin-treated adults with type 2 diabetes and risk factors for hypoglycaemia. Diabetes Obes Metab 2021; 23: 2572-81.
 
44.
AlMalki MH, Aldesokey H, Alkhafaji D, et al. Glycaemic control in people with type 2 diabetes treated with insulin degludec: a real-world, prospective non-interventional study-UPDATES Saudi Arabia. Adv Ther 2023; 40: 568-84.
 
45.
Carroll MF, Schade DS. The dawn phenomenon revisited: implications for diabetes therapy. Endocr Pract 2005; 11: 55-64.
 
46.
Alexopoulos AS, Blair R, Peters AL. Management of preexisting diabetes in pregnancy: a review. JAMA 2019; 321: 1811-9.
 
47.
Benhalima K, Beunen K, Siegelaar SE, et al. Management of type 1 diabetes in pregnancy: update on lifestyle, pharmacological treatment, and novel technologies for achieving glycaemic targets. Lancet Diabetes Endocrinol 2023; 11: 490-508.
 
ISSN:2451-0629
Journals System - logo
Scroll to top