The Risk of Multiple Myeloma Is Reduced in Metformin Initiators: A Retrospective Cohort Study in Taiwanese Patients with Type 2 Diabetes Mellitus

Abstract

Background: Whether metformin might reduce the risk of multiple myeloma (MM) has not been extensively researched in humans. Methods: The study subjects were enrolled from the reimbursement database of Taiwan’s National Health Insurance. A total of 739,553 patients who had a new diagnosis of type 2 diabetes mellitus during 1999–2009 were identified. They were categorized as metformin initiators (metformin (+)) and non-metformin initiators (metformin (−)) based on the prescriptions of antidiabetic drugs that included metformin and did not include metformin within the initial 12 months, respectively. MM incidence was calculated after the initial 12 months of treatment group assignment until 31 December 2011. Hazard ratios based on intention-to-treat (ITT) and per-protocol (PP) approaches were estimated by Cox regression weighted by propensity scores. Results: In the ITT analyses, the respective incidence rates for 497,248 metformin (+) and 242,305 metformin (−) were 9.97 and 14.33 per 100,000 person-years. The hazard ratio that compared metformin (+) to metformin (−) in the ITT analysis was 0.710 (95% confidence interval 0.593–0.850). In the PP analysis, the respective incidence rates were 5.14 and 13.98 per 100,000 person-years, and the hazard ratio was 0.355 (95% confidence interval, 0.270–0.466). The lower risk of MM among metformin (+) was supported by subgroup and sensitivity analyses. Conclusions: Type 2 diabetes patients who are initiated with metformin treatment have a significantly lower risk of MM, especially when they adhere to metformin treatment.

Metformin and risk of hematological cancers in patients with diabetes: a systematic review and meta-analysis

“…Finally, 11 studies (18 effect sizes) with a total sample size of 2 318 217 participants and 6280 HCs cases, published between 2010 and 2023, were eligible ( Figure 1 ). 4 , 5 , 8 , 19 , 20 , 29 – 34 Some studies reported multiple effect sizes derived from their stratified analysis based on type of cancer or the gender of participants; we extracted all appropriate effect sizes to perform the meta-analyses. Nine of the articles were retrospective or prospective cohort studies; 5 , 19 , 20 , 29 , 30 , 32 – 34 two were nested case-control studies.…”

“… 17 , 18 Despite the promising results observed in preclinical studies, the association between metformin use and the risk of HCs in humans remains unclear; several observational studies have investigated this relationship, with conflicting results. 19 , 20 These studies have been limited by small sample sizes, the potential for confounding factors, and variability in the characteristics of the populations studied. Our analysis were performed to synthesize the available evidence from observational studies to provide more robust estimates of the association of metformin use in patients T2DM with the risk of HCs.…”

Metformin and chidamide synergistically suppress multiple myeloma progression and enhance lenalidomide/bortezomib sensitivity

“…[31][32][33] A study has also revealed that type II diabetes patients who received metformin treatment have an obviously lower risk of MM. 34 Chidamide is a new oral benzamide-type selective HDAC inhibitor with anticancer activity in multiple cancers, such as hematologic cancer, lung carcinoma, and laryngeal carcinoma. [35][36][37] The HDAC inhibition and anticancer effects of chidamide have also been identified in MM development.…”

“…Metformin shows anticancer activities in various malignancies, including colorectal cancer, thyroid cancer along with head and neck cancer 31–33 . A study has also revealed that type II diabetes patients who received metformin treatment have an obviously lower risk of MM 34 . Chidamide is a new oral benzamide‐type selective HDAC inhibitor with anticancer activity in multiple cancers, such as hematologic cancer, lung carcinoma, and laryngeal carcinoma 35–37 .…”

Obesity and myeloma: Clinical and mechanistic contributions to disease progression

“…Likewise, a cohort of US veterans with comorbid MGUS and diabetes mellitus (DM) treated with metformin displayed reduction in myeloma risk with metformin exposure >4 years (21). Similarly, in a recently study of 739,553 patients from Taiwan's National Health Insurance database, T2DM patients who were prescribed metformin within the first year of their diagnosis with T2DM had a lower risk of developing MM compared to T2DM patients who were not prescribed metformin (42).…”