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
. 2024 May 30:2024:3470654.
doi: 10.1155/2024/3470654. eCollection 2024.

Treating Type 2 Diabetes With Early, Intensive, Multimodal Pharmacotherapy: Real-World Evidence From an International Collaborative Database

Matthew Anson  1 , Ayesha Malik  2 , Sizheng S Zhao  3 , Philip Austin  4 , Gema H Ibarburu  4 , Shabbar Jaffar  5 , Anupam Garrib  5 , Daniel J Cuthbertson  6 , Uazman Alam  1   7
Affiliations

Treating Type 2 Diabetes With Early, Intensive, Multimodal Pharmacotherapy: Real-World Evidence From an International Collaborative Database

Matthew Anson et al. J Diabetes Res. .

Abstract

Aims: We compared the glycaemic and cardiorenal effects of combination therapy involving metformin, pioglitazone, sodium-glucose-linked-cotransporter-2 inhibitor (SGLT2i), and glucagon-like peptide-1 receptor agonist (GLP-1RA) versus a more conventional glucocentric treatment approach combining sulphonylureas (SU) and insulin from the point of type 2 diabetes (T2D) diagnosis. Methods: We performed a retrospective cohort study using the Global Collaborative Network in TriNetX. We included individuals prescribed metformin, pioglitazone, an SGLT2i, and a GLP-1 RA for at least 1-year duration, within 3 years of a T2D diagnosis, and compared with individuals prescribed insulin and a SU within the same temporal pattern. Individuals were followed up for 3 years. Results: We propensity score-matched (PSM) for 26 variables. A total of 1762 individuals were included in the final analysis (n = 881 per cohort). At 3-years, compared to the insulin/SU group, the metformin/pioglitazone/SGLT2i/GLP-1 RA group had a lower risk of heart failure (HR 0.34, 95% CI 0.13-0.87, p = 0.018), acute coronary syndrome (HR 0.29, 95% CI 0.12-0.67, p = 0.002), stroke (HR 0.17, 95% CI 0.06-0.49, p < 0.001), chronic kidney disease (HR 0.50, 95% CI 0.25-0.99, p = 0.042), and hospitalisation (HR 0.59, 95% CI 0.46-0.77, p < 0.001). Conclusions: In this real-world study, early, intensive polytherapy, targeting the distinct pathophysiological defects in T2D, is associated with significantly more favourable cardiorenal outcomes, compared to insulin and SU therapy.

Keywords: cardiovascular outcomes; ominous octet; pioglitazone; type 2 diabetes.

PubMed Disclaimer

Conflict of interest statement

M. A. receives a salary from the Pain Relief Foundation. P. A. and G. H. I. are employees of TriNetX LLC. D. J. C. has received investigator-initiated grants from AstraZeneca and Novo Nordisk and support for education from Perspectum. U. A. has received honoraria from Procter & Gamble, Viatris, Grunenthal, and Sanofi for educational meetings. U. A. has also received investigator-led funding from Procter & Gamble. All other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(a) Clinical outcomes over 3 years as a forest plot. Green boxes represent statistically significant findings. (b) Adverse clinical outcomes over 3 years as a forest plot. Green boxes represent statistically significant findings. IHD: ischaemic heart disease; ACS: acute coronary syndrome; CKD: chronic kidney disease; HHS: hyperosmolar hyperglycaemic state; DKA: diabetic ketoacidosis; UTI: urinary tract infection.
Figure 2
Figure 2
(a) Change in HbA1c over 3 years. Blue line represents the “insulin + sulphonylurea” group and black line represents the “MTF/TZD/GLP-1 RA/SGLT2i” group. (b) Change in weight over 3 years. Blue line represents the “insulin + sulphonylurea” group and black line represents the “MTF/TZD/GLP-1 RA/SGLT2i” group. (c) Change in eGFR over 3 years. Blue line represents the “insulin + sulphonylurea” group and black line represents the “MTF/TZD/GLP-1 RA/SGLT2i” group.
Figure 3
Figure 3
Change in HbA1c over time.
See this image and copyright information in PMC

References

    1. Saeedi P., Petersohn I., Salpea P., et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Research and Clinical Practice . 2019;157, article 107843 doi: 10.1016/j.diabres.2019.107843. - DOI - PubMed
    1. Caro J. J., Ward A. J., O’Brien J. A. Lifetime costs of complications resulting from type 2 diabetes in the U.S. Diabetes Care . 2002;25(3):476–481. doi: 10.2337/diacare.25.3.476. - DOI - PubMed
    1. DeFronzo R. A. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes . 2009;58(4):773–795. doi: 10.2337/db09-9028. - DOI - PMC - PubMed
    1. Zhu N. A., Harris S. B. Therapeutic inertia in people with type 2 diabetes in primary care: a challenge that just won’t go away. Diabetes Spectrum . 2020;33(1):44–49. doi: 10.2337/ds19-0016. - DOI - PMC - PubMed
    1. Engler C., Leo M., Pfeifer B., et al. Long-term trends in the prescription of antidiabetic drugs: real-world evidence from the diabetes registry Tyrol 2012–2018. BMJ Open Diabetes Research & Care . 2020;8(1, article e001279) doi: 10.1136/bmjdrc-2020-001279. - DOI - PMC - PubMed

MeSH terms