Efficacy of Regimens in the Treatment of Latent Autoimmune Diabetes in Adults: A Network Meta-analysis

Overview

Journal Diabetes Ther

Specialty Cardiology & Vascular Diseases

Date 2023 Aug 16

PMID 37584857

Authors

Wanqing Wang

Fei Huang

Chunchao Han

Affiliations

Soon will be listed here.

Abstract

Introduction: Latent autoimmune diabetes in adults (LADA) is a highly heterogeneous autoimmune condition with clinical and genetic characteristics that fall between those of type 1 diabetes mellitus and type 2 diabetes mellitus; therefore, there are no uniform criteria for the selection of therapeutic agents. We conducted a network meta-analysis to evaluate the efficacy of various therapeutic agents for LADA by comparing their effects on various indicators used to reflect LADA.

Methods: We searched the PubMed, Cochrane Library, Embase and Web of Science databases from their inception to March 2023 and collected data from 14 randomized controlled trials on glucose-lowering drugs for LADA, including 23 studies and 15 treatment regimens. The effectiveness of drugs was ranked and evaluated by combining surface under the cumulative ranking (SUCRA) plots and forest plots. Factors that may influence study heterogeneity were also searched and analyzed by combining subgroup analysis, publication bias, funnel plots and sensitivity analysis.

Results: The results of the network meta-analysis showed that insulin had the most significant effect on the control of change from baseline in glycosylated hemoglobin, type A1 (ΔHbA1c). Insulin combined with dipeptidyl peptidase-4 (DPP-4) inhibitors performed the best in reducing fasting blood glucose and body mass index. Treatment regimens involving thiazolidinediones were the most advantageous in HbA1c, fasting C-peptide and postprandial C-peptide control. Longer dosing may be more beneficial in maintaining islet β-cell function in the LADA population.

Conclusion: LADA is an immune condition with high heterogeneity, and treatment should be administered according to the C-peptide level of the LADA population. For this population with LADA with a certain level of β-cell function, combinations of insulin with DPP-4 inhibitors or thiazolidinediones probably can be more effective treatment options to maintain islet function and normal blood glucose.

Trial Registration: PROSPERO CRD42023410795.

Citing Articles

Exploring a Synergistic Approach: Dual GLP-1 Agonist Combined with Degludec Basal Insulin for Early Type 1 Diabetes Treatment and its Impact on Albumin-Insulin Producing Cells Expression.

Ahmed A, Akl M Adv Pharm Bull. 2024; 14(2):262-265.

PMID: 39206389 PMC: 11347740. DOI: 10.34172/apb.2024.040.

References

Buzzetti R, Maddaloni E, Gaglia J, Leslie R, Wong F, Boehm B . Adult-onset autoimmune diabetes. Nat Rev Dis Primers. 2022; 8(1):63. DOI: 10.1038/s41572-022-00390-6. View

Leslie R, Kolb H, Schloot N, Buzzetti R, Mauricio D, de Leiva A . Diabetes classification: grey zones, sound and smoke: Action LADA 1. Diabetes Metab Res Rev. 2008; 24(7):511-9. DOI: 10.1002/dmrr.877. View

Irvine W, McCallum C, Gray R, Duncan L . Clinical and pathogenic significance of pancreatic-islet-cell antibodies in diabetics treated with oral hypoglycaemic agents. Lancet. 1977; 1(8020):1025-7. DOI: 10.1016/s0140-6736(77)91258-2. View

Turner R, Stratton I, Horton V, Manley S, Zimmet P, Mackay I . UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet. 1997; 350(9087):1288-93. DOI: 10.1016/s0140-6736(97)03062-6. View

van Deutekom A, Heine R, Simsek S . The islet autoantibody titres: their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitus. Diabet Med. 2007; 25(2):117-25. DOI: 10.1111/j.1464-5491.2007.02316.x. View

Dellepiane S, Ben Nasr M, Assi E, Usuelli V, Letizia T, DAddio F . Sodium glucose cotransporters inhibitors in type 1 diabetes. Pharmacol Res. 2018; 133:1-8. DOI: 10.1016/j.phrs.2018.04.018. View

Cernea S, Buzzetti R, Pozzilli P . Beta-cell protection and therapy for latent autoimmune diabetes in adults. Diabetes Care. 2009; 32 Suppl 2:S246-52. PMC: 2811444. DOI: 10.2337/dc09-S317. View

Buzzetti R, Tuomi T, Mauricio D, Pietropaolo M, Zhou Z, Pozzilli P . Management of Latent Autoimmune Diabetes in Adults: A Consensus Statement From an International Expert Panel. Diabetes. 2020; 69(10):2037-2047. PMC: 7809717. DOI: 10.2337/dbi20-0017. View

Morieri M, Raz I, Consoli A, Rigato M, Lapolla A, Broglio F . Short-term effectiveness of dapagliflozin versus DPP-4 inhibitors in elderly patients with type 2 diabetes: a multicentre retrospective study. J Endocrinol Invest. 2023; 46(7):1429-1439. PMC: 10261249. DOI: 10.1007/s40618-022-02002-2. View

10.

Pozzilli P, Leslie R, Peters A, Buzzetti R, Shankar S, Milicevic Z . Dulaglutide treatment results in effective glycaemic control in latent autoimmune diabetes in adults (LADA): A post-hoc analysis of the AWARD-2, -4 and -5 Trials. Diabetes Obes Metab. 2018; 20(6):1490-1498. DOI: 10.1111/dom.13237. View

11.

Bendotti G, Montefusco L, Lunati M, Usuelli V, Pastore I, Lazzaroni E . The anti-inflammatory and immunological properties of GLP-1 Receptor Agonists. Pharmacol Res. 2022; 182:106320. DOI: 10.1016/j.phrs.2022.106320. View

12.

Jones A, McDonald T, Shields B, Hill A, Hyde C, Knight B . Markers of β-Cell Failure Predict Poor Glycemic Response to GLP-1 Receptor Agonist Therapy in Type 2 Diabetes. Diabetes Care. 2015; 39(2):250-7. PMC: 4894547. DOI: 10.2337/dc15-0258. View

13.

Yang Z, Zhou Z, Li X, Huang G, Lin J . Rosiglitazone preserves islet beta-cell function of adult-onset latent autoimmune diabetes in 3 years follow-up study. Diabetes Res Clin Pract. 2008; 83(1):54-60. DOI: 10.1016/j.diabres.2008.09.044. View

14.

Agardh C, Lynch K, Palmer M, Link K, Lernmark A . GAD65 vaccination: 5 years of follow-up in a randomised dose-escalating study in adult-onset autoimmune diabetes. Diabetologia. 2009; 52(7):1363-8. DOI: 10.1007/s00125-009-1371-2. View

15.

Li X, Liao L, Yan X, Huang G, Lin J, Lei M . Protective effects of 1-alpha-hydroxyvitamin D3 on residual beta-cell function in patients with adult-onset latent autoimmune diabetes (LADA). Diabetes Metab Res Rev. 2009; 25(5):411-6. DOI: 10.1002/dmrr.977. View

16.

Nowrouzi-Sohrabi P, Tabrizi R, Jalali M, Jamali N, Rezaei S, Hessami K . Effects of Diacerein Intake on Cardiometabolic Profiles in Type 2 Diabetics: A Systematic Review and Meta-Analysis of Clinical Trials. Curr Med Chem. 2020; 28(4):840-852. DOI: 10.2174/0929867327666200728134755. View

17.

Ko Y, Lee W, Park J, Kim H, Sim J, Tannaphai P . Diagnostic sensitivity and specificity of 2-mSv CT vs. conventional-dose CT in adolescents and young adults with suspected appendicitis: post hoc subgroup analysis of the LOCAT data. Eur Radiol. 2020; 30(8):4573-4585. DOI: 10.1007/s00330-020-06811-y. View

18.

Iwamoto N, Matsui A, Kazama H, Oura T . Subgroup Analysis Stratified by Baseline Pancreatic β-cell Function in a Japanese Study of Dulaglutide in Patients with Type 2 Diabetes. Diabetes Ther. 2017; 9(1):383-394. PMC: 5801232. DOI: 10.1007/s13300-017-0346-4. View

19.

Altobelli E, Del Negro V, Angeletti P, Latella G . Low-FODMAP Diet Improves Irritable Bowel Syndrome Symptoms: A Meta-Analysis. Nutrients. 2017; 9(9). PMC: 5622700. DOI: 10.3390/nu9090940. View

20.

Guo T, Ren L, Wang Q, Li K . A network meta-analysis of updated haemostatic strategies for hysterectomy. Int J Surg. 2016; 35:187-195. DOI: 10.1016/j.ijsu.2016.10.002. View