Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 May 1;48(5):671-681.
doi: 10.2337/dci24-0104.

The Modern Role of Basal Insulin in Advancing Therapy in People With Type 2 Diabetes

Geremia B Bolli  1 , Philip D Home  2 , Francesca Porcellati  1 , Matthew C Riddle  3 , Hertzel C Gerstein  4 , Paola Lucidi  5 , Carmine G Fanelli  1 , David R Owens  6
Affiliations
Review

The Modern Role of Basal Insulin in Advancing Therapy in People With Type 2 Diabetes

Geremia B Bolli et al. Diabetes Care. .

Abstract

Insulin deficiency, often aggravated by insulin resistance, results in type 2 diabetes mellitus (T2DM). With the availability of glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, basal insulin (BI) therapy is no longer the first-line option after lifestyle modification plus oral agents is insufficient. In contrast to BI, the newer medications require minor titration, lower hyperglycemia in a glucose-dependent manner, and reduce body weight. Importantly, the newer agents reduce cardiorenal events in the short term. Nonetheless, insulin therapy continues to play a key role in control of hyperglycemia and therefore long-term prevention of vascular complications. Its use is essential in many circumstances, including metabolic emergencies, new diabetes onset, latent autoimmune diabetes (LADA), pregnancy, and when other agents are less desirable due to comorbidities. BI is needed in the frequent condition of failure of other therapies to keep HbA1c to target and/or intolerance of them. There are several advantages to the combination of BI with the newer medications given their different but complementary mechanisms of action, primarily, the lower dose of each, improving adherence and outcomes while decreasing the side effects. Multiple choices for single or combination use can better meet the variety of clinical phenotypes in the heterogeneous T2DM population, using the tenets of precision medicine.

PubMed Disclaimer

Conflict of interest statement

Duality of Interest. G.B.B. has received honoraria for lecturing from Sanofi. P.D.H. receives research support from Sanofi and has consulted for Sanofi, Novo Nordisk, and Eli Lilly and manufacturers of biosimilar insulins. F.P. receives clinical trial funding and advisory board and lecture fees from Abbott, AstraZeneca, Lilly, Novo Nordisk, and Sanofi. H.C.G. holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly, Novo Nordisk, and Hanmi Pharmaceutical; continuing education grants from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Novo Nordisk, Zuellig Pharma, and Jiangsu Hanson; and consulting fees from Abbott, Bayer, Eli Lilly, Novo Nordisk, Pfizer, Sanofi, and Hanmi Pharmaceutical. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
PG and insulin concentrations and rates of EGP and glucose utilization (GU) during overnight fasting in 8 individuals without diabetes (△) and 11 untreated individuals with recently diagnosed T2DM studied once with saline infusion (●) and once with feedback intravenous insulin infusion from 2400 to 1000 h (mean ± SD rate 0.62 ± 0.11 units/h) with PG target 100 mg/dL (○). Data (means ± SD) were collected as part of a previous study (23).
Figure 2
Figure 2
Crossover (n = 6, individuals with BI-treated T2DM) comparison of the effect of titrated doses of NPH insulin (●) and insulin glargine (○) 100 units/mL (dosing at 2200 h) on plasma insulin versus glucose concentration, and rates of EGP and glucose utilization (GU) overnight. Dinner had been at 1800 h. Data for eight matched individuals without diabetes (△) are shown for comparison. Data are means ± SD. Unpublished data are included from pilot clamps performed for a study previously described (27).
Figure 3
Figure 3
Metabolic outcomes of individual and combined treatments with BI, GLP-1RA, and SGLT2i. Cardiorenal-protective effects of GLP-1RA and SGLT2i are not represented here. Long-term protective effects of HbA1c at target through BI on macroangiopathy also are not represented.
See this image and copyright information in PMC

References

    1. Owens DR, Zinman B, Bolli GB.. Insulins today and beyond. Lancet 2001;358:739–746 - PubMed
    1. Gerstein HC, Rutty CJ.. Insulin therapy: the discovery that shaped a century. Can J Diabetes 2021;45:798–803 - PubMed
    1. Davies MJ, Aroda VR, Collins BS, 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;45:2753–2786 - PMC - PubMed
    1. Inzucchi SE, Bergenstal RM, Buse JB, et al. . Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015;38:140–149 - PubMed
    1. Gutgesell RM, Nogueiras R, Tschöp MH, Müller TD.. Dual and triple incretin-based co-agonists: novel therapeutics for obesity and diabetes. Diabetes Ther 2024;15:1069–1084 - PMC - PubMed

MeSH terms