Short-acting insulin analogues vs. regular human insulin in type 2 diabetes: a meta-analysis
Abstract
Aim Short-acting insulin analogues, in comparison with regular human insulin (HRI), provide a greater control of postprandial glucose, while their superiority on haemoglobin A1c (HbA1c) is controversial. Method All randomized controlled trials (RCTs) with a duration >4 weeks comparing short-acting insulin analogues (lispro, aspart or glulisine) with HRI in type 2 diabetic patients were retrieved; data on HbA1c and postprandial glucose et end-point and incidence of severe hypoglycaemia were extracted and meta-analysed. Results A total of 13 RCTs (7, 4 and 2 with lispro, aspart and glulisine, respectively) were retrieved and included in the analysis. Short-acting analogues reduced HbA1c by 0.4% (0.1-0.6%) (p = 0.027) in comparison with HRI. A significant improvement was observed also in self-monitored 2 h postbreakfast and dinner blood glucose. The overall rate of severe hypoglycaemia was not significantly different with short-acting analogues and HRI [Mantel-Haenszel odds ratio for 95% confidence interval 0.61 (0.25-1.45)]. Conclusion In type 2 diabetic patients, short-acting insulin analogues provide a better control of HbA1c and postprandial glucose than regular human insulin, without any significant reduction of the risk of severe hypoglycaemia.
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Meta-analyses of trials comparing rapid-acting insulin analogs with human regular insulin in type 2 diabetes have not reported meaningful differences in A1C or hypoglycemia.
“Meta-analyses of trials comparing rapid-acting insulin analogs with human regular insulin in type 2 diabetes have not reported meaningful differences in A1C or hypoglycemia (175,176).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [175]
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9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2021</i>
American Diabetes Association (2021) · Diabetes Care · doi:10.2337/dc21-s009 · Cited by 972 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2020</i>
American Diabetes Association (2020) · Diabetes Care · doi:10.2337/dc20-s009 · Cited by 914 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Care in Diabetes—2023</i>
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Hilliard, M. E., Isaacs, D., Johnson, E. L., et al. (2023) · Diabetes Care · doi:10.2337/dc23-s009 · Cited by 851 · see citing works
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American Diabetes Association (2019) · Diabetes Care · doi:10.2337/dc19-s009 · Cited by 739 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Bajaj, M., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s009 · Cited by 728 · see citing works
Pharmacologic Glycemic Management of Type 2 Diabetes in Adults: 2020 Update
Lipscombe, L., Butalia, S., Dasgupta, K., Eurich, D. T., MacCallum, L., Shah, B. R., Simpson, S., & Senior, P. A. (2020) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2020.08.001 · Cited by 153 · see citing works
Pharmacologic management of type 2 diabetes
Harper, W., Clement, M., Goldenberg, R., Hanna, A., Main, A., Retnakaran, R., Sherifali, D., Woo, V., & Yale, J.-F. (2013) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2013.01.021 · Cited by 138 · see citing works
Mannucci, E., Caiulo, C., Naletto, L., Madama, G., & Monami, M. (2021) · Endocrine · doi:10.1007/s12020-021-02889-6 · Cited by 30 · see citing works
Self-citation
- Authors
- Mannucci, E., Monami, M., & Marchionni, N.
- Affiliations
- Azienda Ospedaliero-Universitaria Careggi (IT)
- Corresponding author
- Mannucci, E.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2008-12-22
- Volume
- 11
- Issue
- 1
- Pages
- 53-59
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2150197163
- Cited by
- 96
- References
- 0
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 4 · 2014: 3 · 2013: 10 · 2012: 7
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- short-acting insulin analogues, regular insulin, type 2 diabetes, insulin lispro, insulin aspart, glulisine, HbA1c, postprandial blood glucose, severe hypoglycemia, glycemic control
- MeSH terms
- Blood Glucose, Diabetes Mellitus, Type 2, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Randomized Controlled Trials as Topic
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