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Published in: Diabetology & Metabolic Syndrome 1/2024

Open Access 01-12-2024 | Insulins | Review

Efficacy and Safety of Once-Weekly Insulin Regimes on Glycemic Control for Type 2 Diabetes: A Systematic Review and Network Meta-analysis

Authors: Peng Wang, Yu Zhang, Wenhao Xu, Jialing He, Liyuan Peng, Yuning Feng, Ping Xu, Weelic Chong, Yang Hai, Lu Jia, Fang Fang

Published in: Diabetology & Metabolic Syndrome | Issue 1/2024

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Abstract

Background

Randomized controlled trials have found that once-weekly insulin resulted in greater glycemic control compared to once-daily insulin in patients with type 2 diabetes. However, no direct comparisons have been made between different types of once-weekly insulin thus far. This systematic review and network meta-analysis aimed to evaluate the effect of the two most advanced once-weekly insulin analogues, namely insulin icodec and insulin Fc, in patients with type 2 diabetes.

Methods

We conducted a thorough search in the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The search included articles published from the beginning to October 10, 2023, with no language limitations. Our aim was to conduct a systematic review of randomized controlled trials that investigated the effectiveness and safety of once-weekly insulin in individuals with type 2 diabetes. Our primary outcome was to evaluate excellent glycemic control, defined as patients achieving glycated hemoglobin levels below 7%.

Results

We identified a total of 7 trials involving 2829 patients. The results showed that once-weekly insulin icodec is more effective than once-weekly insulin Fc (RR 1.59 [95% CI 1.08–2.38]), once-daily degludec (RR 1.43 [95% CI 1.14–1.83]), and once-daily glargine (RR 1.15 [95% CI 1.00-1.41]). Moreover, the incidence of severe hypoglycemia was lower with once-weekly insulin icodec compared to once-daily degludec (RR 0.00016 [95% CI 0 to 0.41]). However, no significant difference in the incidence of severe hypoglycemia was observed between once-weekly insulin icodec and once-daily glargine (RR 0.39 [95% CI 0.03 to 4.83]).

Conclusions

In patients with type 2 diabetes, once-weekly insulin icodec achieved superior glycemic control compared to once-weekly insulin Fc, with no significant difference in the occurrence of hypoglycemia. The ranking probability results have shown that one weekly icodec seems to be the preferred option in patients with type 2 diabetes.

Trial registration

PROSPERO Identifier: CRD42023470894.
Appendix
Available only for authorised users
Literature
1.
go back to reference ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. 9. Pharmacologic approaches to Glycemic Treatment: standards of Care in Diabetes-2023. Diabetes Care. 2023;46:140–s57.CrossRef ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. 9. Pharmacologic approaches to Glycemic Treatment: standards of Care in Diabetes-2023. Diabetes Care. 2023;46:140–s57.CrossRef
2.
go back to reference Rosenstock J, Del Prato S. Basal weekly insulins: the way of the future! Metabolism. 2022;126:154924.CrossRefPubMed Rosenstock J, Del Prato S. Basal weekly insulins: the way of the future! Metabolism. 2022;126:154924.CrossRefPubMed
3.
go back to reference Frias J, Chien J, Zhang Q, Chigutsa E, Landschulz W, Syring K, et al. Safety and efficacy of once-weekly basal insulin fc in people with type 2 Diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 study. Lancet Diabetes Endocrinol. 2023;11:158–68.CrossRefPubMed Frias J, Chien J, Zhang Q, Chigutsa E, Landschulz W, Syring K, et al. Safety and efficacy of once-weekly basal insulin fc in people with type 2 Diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 study. Lancet Diabetes Endocrinol. 2023;11:158–68.CrossRefPubMed
4.
go back to reference Lingvay I, Asong M, Desouza C, Gourdy P, Kar S, Vianna A, et al. Once-weekly insulin Icodec vs once-daily insulin degludec in adults with insulin-naive type 2 Diabetes: the ONWARDS 3 Randomized Clinical Trial. JAMA. 2023;330:228–37.CrossRefPubMedPubMedCentral Lingvay I, Asong M, Desouza C, Gourdy P, Kar S, Vianna A, et al. Once-weekly insulin Icodec vs once-daily insulin degludec in adults with insulin-naive type 2 Diabetes: the ONWARDS 3 Randomized Clinical Trial. JAMA. 2023;330:228–37.CrossRefPubMedPubMedCentral
5.
go back to reference Mathieu C, Ásbjörnsdóttir B, Bajaj HS, Lane W, Matos A, Murthy S, et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 Diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023;401:1929–40.CrossRefPubMed Mathieu C, Ásbjörnsdóttir B, Bajaj HS, Lane W, Matos A, Murthy S, et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 Diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023;401:1929–40.CrossRefPubMed
6.
go back to reference Philis-Tsimikas A, Asong M, Franek E, Jia T, Rosenstock J, Stachlewska K, et al. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 Diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial. Lancet Diabetes Endocrinol. 2023;11:414–25.CrossRefPubMed Philis-Tsimikas A, Asong M, Franek E, Jia T, Rosenstock J, Stachlewska K, et al. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 Diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial. Lancet Diabetes Endocrinol. 2023;11:414–25.CrossRefPubMed
7.
go back to reference Rosenstock J, Bain SC, Gowda A, Jódar E, Liang B, Lingvay I, et al. Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without previous insulin. N Engl J Med. 2023;389:297–308.CrossRefPubMed Rosenstock J, Bain SC, Gowda A, Jódar E, Liang B, Lingvay I, et al. Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without previous insulin. N Engl J Med. 2023;389:297–308.CrossRefPubMed
8.
go back to reference Sutton A, Ades AE, Cooper N, Abrams K. Use of indirect and mixed treatment comparisons for technology assessment. PharmacoEconomics. 2008;26:753–67.CrossRefPubMed Sutton A, Ades AE, Cooper N, Abrams K. Use of indirect and mixed treatment comparisons for technology assessment. PharmacoEconomics. 2008;26:753–67.CrossRefPubMed
9.
go back to reference Jansen JP, Trikalinos T, Cappelleri JC, Daw J, Andes S, Eldessouki R, et al. Indirect treatment comparison/network meta-analysis study questionnaire to assess relevance and credibility to inform health care decision making: an ISPOR-AMCP-NPC Good Practice Task Force report. Value Health. 2014;17:157–73.CrossRefPubMed Jansen JP, Trikalinos T, Cappelleri JC, Daw J, Andes S, Eldessouki R, et al. Indirect treatment comparison/network meta-analysis study questionnaire to assess relevance and credibility to inform health care decision making: an ISPOR-AMCP-NPC Good Practice Task Force report. Value Health. 2014;17:157–73.CrossRefPubMed
10.
go back to reference Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.CrossRefPubMedPubMedCentral Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.CrossRefPubMedPubMedCentral
11.
go back to reference Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162:777–84.CrossRefPubMed Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162:777–84.CrossRefPubMed
12.
go back to reference Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.CrossRefPubMed Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.CrossRefPubMed
13.
go back to reference Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–6.CrossRefPubMedPubMedCentral Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–6.CrossRefPubMedPubMedCentral
14.
go back to reference van Valkenhoef G, Lu G, de Brock B, Hillege H, Ades AE, Welton NJ. Automating network meta-analysis. Res Synth Methods. 2012;3:285–99.CrossRefPubMed van Valkenhoef G, Lu G, de Brock B, Hillege H, Ades AE, Welton NJ. Automating network meta-analysis. Res Synth Methods. 2012;3:285–99.CrossRefPubMed
15.
go back to reference O’Rourke K, Altman DG. Bayesian random effects meta-analysis of trials with binary outcomes: methods for the absolute risk difference and relative risk scales. Stat Med. 2005;24:2733–42. author reply 43.PubMed O’Rourke K, Altman DG. Bayesian random effects meta-analysis of trials with binary outcomes: methods for the absolute risk difference and relative risk scales. Stat Med. 2005;24:2733–42. author reply 43.PubMed
16.
go back to reference Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol. 2011;64:163–71.CrossRefPubMed Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol. 2011;64:163–71.CrossRefPubMed
17.
go back to reference Bajaj HS, Bergenstal RM, Christoffersen A, Davies MJ, Gowda A, Isendahl J, et al. Switching to once-weekly insulin Icodec Versus once-daily insulin glargine U100 in type 2 Diabetes inadequately controlled on daily basal insulin: a phase 2 Randomized Controlled Trial. Diabetes Care. 2021;44:1586–94.CrossRefPubMedPubMedCentral Bajaj HS, Bergenstal RM, Christoffersen A, Davies MJ, Gowda A, Isendahl J, et al. Switching to once-weekly insulin Icodec Versus once-daily insulin glargine U100 in type 2 Diabetes inadequately controlled on daily basal insulin: a phase 2 Randomized Controlled Trial. Diabetes Care. 2021;44:1586–94.CrossRefPubMedPubMedCentral
18.
go back to reference Bue-Valleskey JM, Kazda CM, Ma C, Chien J, Zhang Q, Chigutsa E, et al. Once-weekly basal insulin fc demonstrated similar Glycemic Control to once-daily insulin degludec in insulin-naive patients with type 2 Diabetes: a phase 2 Randomized Control Trial. Diabetes Care. 2023;46:1060–7.CrossRefPubMedPubMedCentral Bue-Valleskey JM, Kazda CM, Ma C, Chien J, Zhang Q, Chigutsa E, et al. Once-weekly basal insulin fc demonstrated similar Glycemic Control to once-daily insulin degludec in insulin-naive patients with type 2 Diabetes: a phase 2 Randomized Control Trial. Diabetes Care. 2023;46:1060–7.CrossRefPubMedPubMedCentral
19.
go back to reference Lingvay I, Buse JB, Franek E, Hansen MV, Koefoed MM, Mathieu C, et al. A randomized, open-label comparison of once-weekly insulin Icodec Titration Strategies Versus once-daily insulin glargine U100. Diabetes Care. 2021;44:1595–603.CrossRefPubMedPubMedCentral Lingvay I, Buse JB, Franek E, Hansen MV, Koefoed MM, Mathieu C, et al. A randomized, open-label comparison of once-weekly insulin Icodec Titration Strategies Versus once-daily insulin glargine U100. Diabetes Care. 2021;44:1595–603.CrossRefPubMedPubMedCentral
20.
go back to reference Rosenstock J, Bajaj HS, Janež A, Silver R, Begtrup K, Hansen MV, et al. Once-weekly insulin for type 2 Diabetes without previous insulin treatment. N Engl J Med. 2020;383:2107–16.CrossRefPubMed Rosenstock J, Bajaj HS, Janež A, Silver R, Begtrup K, Hansen MV, et al. Once-weekly insulin for type 2 Diabetes without previous insulin treatment. N Engl J Med. 2020;383:2107–16.CrossRefPubMed
21.
go back to reference Karakasis P, Patoulias D, Pamporis K, Popovic DS, Stachteas P, Bougioukas KI et al. Efficacy and safety of once-weekly versus once-daily basal insulin analogues in the treatment of type 2 Diabetes Mellitus: a systematic review and meta-analysis. Diabetes Obes Metab. 2023. Karakasis P, Patoulias D, Pamporis K, Popovic DS, Stachteas P, Bougioukas KI et al. Efficacy and safety of once-weekly versus once-daily basal insulin analogues in the treatment of type 2 Diabetes Mellitus: a systematic review and meta-analysis. Diabetes Obes Metab. 2023.
22.
go back to reference Ribeiro ESR, de Miranda Gauza M, Guisso MES, da Silva JON, Kohara SK. Once-weekly insulin Icodec vs. once-daily insulin glargine U100 for type 2 Diabetes: a systematic review and meta-analysis of phase 2 randomized controlled trials. Arch Endocrinol Metab. 2023;67:e000614.CrossRef Ribeiro ESR, de Miranda Gauza M, Guisso MES, da Silva JON, Kohara SK. Once-weekly insulin Icodec vs. once-daily insulin glargine U100 for type 2 Diabetes: a systematic review and meta-analysis of phase 2 randomized controlled trials. Arch Endocrinol Metab. 2023;67:e000614.CrossRef
23.
go back to reference Nishimura E, Pridal L, Glendorf T, Hansen BF, Hubálek F, Kjeldsen T et al. Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing. BMJ Open Diabetes Res Care. 2021;9. Nishimura E, Pridal L, Glendorf T, Hansen BF, Hubálek F, Kjeldsen T et al. Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing. BMJ Open Diabetes Res Care. 2021;9.
24.
go back to reference Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of hyperglycemia in type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45:2753–86.CrossRefPubMedPubMedCentral Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of hyperglycemia in type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45:2753–86.CrossRefPubMedPubMedCentral
Metadata
Title
Efficacy and Safety of Once-Weekly Insulin Regimes on Glycemic Control for Type 2 Diabetes: A Systematic Review and Network Meta-analysis
Authors
Peng Wang
Yu Zhang
Wenhao Xu
Jialing He
Liyuan Peng
Yuning Feng
Ping Xu
Weelic Chong
Yang Hai
Lu Jia
Fang Fang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2024
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-023-01240-5

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