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ABCIC
Editorial

Metformin in Combination with Immune Checkpoint Inhibitors: Myocardial FDG Uptake Can Predict Prognosis?

Claudio Tinoco Mesquita et al. Ana Beatriz Couto Marina Schmid Nunes Fernanda Azevedo Silva

In Brazil, the estimate for 2023-2025 indicates that there will be 704,000 new cancer cases in the country, 221,000 of which will be non-melanoma skin cancers, cited as the most common type. After this type of cancer, breast cancer has the highest incidence, with 74,000 cases, followed by prostate cancer, with 72,000 cases, colorectum cancer, with 46,000 cases, and lung cancer, with 32,000 new cases. The cancer epidemiological profile in Brazil is like countries with a high income; however, it differs when analyzed by region, indicating significant regional inequalities. While in the country’s more developed regions (South and Southeast), the age-adjusted incidence rates range between 180 and 190 cases per 100,000 inhabitants, in less developed regions (North and Northeast), these rates vary from 157 to 164 cases per 100,000 inhabitants. The highest cancer mortality in Brazil is due to lung cancer (13.7% of cancer deaths), followed by colorectum cancer (10.4% of cancer deaths), and then breast cancer (8% of cancer deaths).

Immune checkpoints, like PD-1, PD-L1, and CTLA-4, regulate the immune system and help to equilibrate immune activation and suppression. They act by avoiding a strong immune response that could attack normal cells. Tumor cells can use these mechanisms to elude the immune system, decreasing its response. The mechanisms used for immune system evasion in lung cancer are linked to PD-1 inhibition, which reduces the activity of tumor immunity cells. Additionally, there is a decrease in T-lymphocyte proliferation and cytokine production (IL-2 and IFN-γ), allowing neoplastic cells to proliferate.

[…]

  • Cardio-Oncology
  • Immune Checkpoint Inhibitors
  • Metformin
  • Positron-Emission Tomography
  • X-Ray Computed Tomography
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Creative Commons Attribution (CC BY) Creative Commons license
11/03/2025 DOI: 10.36660/abcimg.20240111i Views 1
Figure 1
ABCIC
Original Article

Variations in Myocardial FDG Uptake and Metformin Use: Implications for Survival during Immunotherapy

Matheus Coelho Torres et al. Juliana Goes Martins Fagundes Luís Fábio Barbosa Botelho Alinne Fernanda Amaral Verçosa Marcelo Dantas Tavares de Melo

Abstract

Background:

The rise of immune checkpoint inhibitors (ICIs) has significantly improved lung cancer outcomes; however, there is a lack of response prediction protocols. Furthermore, preclinical studies have indicated a promising association between metformin, β-blockers (BBs), and improved cancer patient outcomes.

Objectives:

The primary objective of this study was to investigate metformin’s impact on survival outcomes. The secondary objectives included assessing myocardial FDG uptake variation (change in standardized uptake value [ΔSUV]) during ICI treatment and evaluating the effects of smoking, diabetes, hypertension, and BB usage on survival outcomes.

Methods:

This single-arm, unicentric retrospective cohort study evaluated lung cancer patients who started using ICIs from July 2016 to December 2021. Inclusion criteria were age 18 years or above, lung cancer treated with ICIs (CTLA-4, PD-1, and PD-L1 inhibitors), and having undergone at least two positron emission tomography-computed tomography (PET-CT) scans.

Results:

Fifty-eight patients fulfilled all the inclusion criteria. Metformin users presented a 759-day increase in overall survival (OS) (p = 0.015). A trend of a 161-day increase in progression-free survival was observed in patients with positive myocardial ΔSUV compared to the negative ΔSUV group (p = 0.066), along with a trend of a 285-day increase in favor of BB users (p=0.886).

Conclusion:

The significant association between metformin use and increased OS suggests metformin as a promising adjuvant for ICI therapy. A trend of positive myocardial ΔSUV and improved outcomes may suggest a potential role of PET-CT in response prediction; however, larger studies are necessary to solidify this hypothesis.

  • Cardio-Oncology
  • Cardiotoxicity
  • Immune Checkpoint Inhibitors
  • Metformin
  • Positron Emission Tomography-Computed Tomography
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Creative Commons Attribution (CC BY) Creative Commons license
30/01/2025 DOI: 10.36660/abcimg.20240108i Views 2
Effects of metformin on QT and QTc interval dispersion of diabetic rats
ABC
Artigo Original

Effects of metformin on QT and QTc interval dispersion of diabetic rats

Eunice Cristina da Silva Costa et al. Antonio Ari Gonçalves Miguel Arcanjo Areas Rafael Gustavo Birochi Morgabel

BACKGROUND: Several drugs can cause prolonged QT interval, as well as prolonged QT dispersion (QTd) in electrocardiographic (EKG) recordings. QTd may be a potentially sensitive marker of increased risk of cardiac arrhythmias and sudden cardiac death. Metformin is an effective antihyperglycemic agent used in the treatment of diabetes. However, studies have correlated dose-dependent effects of metformin on glycemia and cardiovascular risk markers. OBJECTIVE: To evaluate the dose-response effects of metformin on QT and QTd of diabetic rats. METHODS: Male Wistar rats were distributed in five groups: non-treated control (C), non-treated diabetics (D), diabetics treated with metmorfin at the doses of 3.5, 30 and 74 µg/kg/bw (DM 3.5, DM 30 and DM 74). Diabetes was induced by an alloxan injection (40 mg/kg, IV). EKG was recorded (days 1, 15 and 30) using four electrodes inserted into the subcutaneous layer of the paws. Both RR and QT intervals were measured, and then corrected QT and QT dispersion values were calculated. RESULTS: The DM 3.5 and DM 30 groups showed a significant reduction of glycemia (p< 0.05) when compared with the high dose (DM 74). Rats of the DM 74 group presented prolonged QTc, QTd and QTcd intervals, whereas rats of the DM 3.5 and DM 30 groups presented less prolonged intervals. CONCLUSION: Metformin at high doses provided greater dispersion of the QT interval probably because of the increased ventricular repolarization inhomogeneity, whereas at low doses decreased QT intervals were observed in diabetic rats.

  • Diabetes Mellitus
  • Electrocardiography
  • Experimental
  • Metformin
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29/05/2008 DOI: 10.1590/S0066-782X2008000400004 Views 2

How to cite this article

EndNote RIS

Electronic Document Format (Vancouver)

Mesquita CT, Couto AB, Nunes MS, Silva FA. Metformin in Combination with Immune Checkpoint Inhibitors: Myocardial FDG Uptake Can Predict Prognosis?. ABC Imagem Cardiovascular 2025;38(1):e20240111.

Electronic Document Format (ABNT)

Mesquita, Claudio Tinoco; Couto, Ana Beatriz; Nunes, Marina Schmid; Silva, Fernanda Azevedo. Metformin in Combination with Immune Checkpoint Inhibitors: Myocardial FDG Uptake Can Predict Prognosis?. ABC Imagem Cardiovascular, v. 38, n. 1, e20240111, Mar. 2025.

Electronic Document Format (APA)

Mesquita, C. T., Couto, A. B., Nunes, M. S., & Silva, F. A. (2025). Metformin in Combination with Immune Checkpoint Inhibitors: Myocardial FDG Uptake Can Predict Prognosis?. ABC Imagem Cardiovascular, 38(1), e20240111.

Electronic Document Format (ISO)

Mesquita, Claudio Tinoco and Couto, Ana Beatriz and Nunes, Marina Schmid and Silva, Fernanda Azevedo. Metformin in Combination with Immune Checkpoint Inhibitors: Myocardial FDG Uptake Can Predict Prognosis?. ABC Imagem Cardiovascular [online]. 2025, vol. 38, n. 1, [cited 2026-10-14], e20240111. Available from: <https://journals.cardiol.br/en/article/metformin-in-combination-with-immune-checkpoint-inhibitors-myocardial-fdg-uptake-can-predict-prognosis/>. ISSN 2318-8219

EndNote RIS

Electronic Document Format (Vancouver)

Torres MC, Fagundes JGM, Botelho LFB, Verçosa AFA, Melo MDT. Variations in Myocardial FDG Uptake and Metformin Use: Implications for Survival during Immunotherapy. ABC Imagem Cardiovascular 2025;38(1):e20240108.

Electronic Document Format (ABNT)

Torres, Matheus Coelho; Fagundes, Juliana Goes Martins; Botelho, Luís Fábio Barbosa; Verçosa, Alinne Fernanda Amaral; Melo, Marcelo Dantas Tavares de. Variations in Myocardial FDG Uptake and Metformin Use: Implications for Survival during Immunotherapy. ABC Imagem Cardiovascular, v. 38, n. 1, e20240108, Jan. 2025.

Electronic Document Format (APA)

Torres, M. C., Fagundes, J. G. M., Botelho, L. F. B., Verçosa, A. F. A., & Melo, M. D. T. (2025). Variations in Myocardial FDG Uptake and Metformin Use: Implications for Survival during Immunotherapy. ABC Imagem Cardiovascular, 38(1), e20240108.

Electronic Document Format (ISO)

Torres, Matheus Coelho and Fagundes, Juliana Goes Martins and Botelho, Luís Fábio Barbosa and Verçosa, Alinne Fernanda Amaral and Melo, Marcelo Dantas Tavares de. Variations in Myocardial FDG Uptake and Metformin Use: Implications for Survival during Immunotherapy. ABC Imagem Cardiovascular [online]. 2025, vol. 38, n. 1, [cited 2026-10-14], e20240108. Available from: <https://journals.cardiol.br/en/article/variations-in-myocardial-fdg-uptake-and-metformin-use-implications-for-survival-during-immunotherapy/>. ISSN 2318-8219

EndNote RIS

Electronic Document Format (Vancouver)

Costa ECS, Gonçalves AA, Areas MA, Morgabel RGB. Effects of metformin on QT and QTc interval dispersion of diabetic rats. Arquivos Brasileiros de Cardiologia 2008;90(4):254-60.

Electronic Document Format (ABNT)

Costa, Eunice Cristina da Silva; Gonçalves, Antonio Ari; Areas, Miguel Arcanjo; Morgabel, Rafael Gustavo Birochi. Effects of metformin on QT and QTc interval dispersion of diabetic rats. Arquivos Brasileiros de Cardiologia, v. 90, n. 4, p. 254-260, May. 2008.

Electronic Document Format (APA)

Costa, E. C. S., Gonçalves, A. A., Areas, M. A., & Morgabel, R. G. B. (2008). Effects of metformin on QT and QTc interval dispersion of diabetic rats. Arquivos Brasileiros de Cardiologia, 90(4), 254-260.

Electronic Document Format (ISO)

Costa, Eunice Cristina da Silva and Gonçalves, Antonio Ari and Areas, Miguel Arcanjo and Morgabel, Rafael Gustavo Birochi. Effects of metformin on QT and QTc interval dispersion of diabetic rats. Arquivos Brasileiros de Cardiologia [online]. 2008, vol. 90, n. 4, [cited 2026-10-14], pp. 254-260. Available from: <https://journals.cardiol.br/en/article/effects-of-metformin-on-qt-and-qtc-interval-dispersion-of-diabetic-rats/>. ISSN 0066-782X

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