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Does Metformin Reduce Risk Of Venous Thromboembolism?

Apr 9, 2019
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Ghazal Blair, Pharm.D. Candidate 2019, LECOM School of Pharmacy

Drug said to be possible fix for multiple primary pathophysiologic abnormalities.

One of the main causes of complications and death in patients with diabetes appears to be vascular disease. The main contributing factor for developing cardiovascular disease in patients with metabolic syndrome and type 2 diabetes mellitus is insulin resistance. Additionally, epidemiological studies reveal a greater risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) within patients with diabetes. DVT often decreases a patient’s ability to do daily activities, however, PE could lead to more complicated and life-threatening conditions. Though the association between diabetes and increased risk of DVT has been established, the underlying factor confounders rather than the effects of diabetes still remains a question.

It has been suggested that metformin, which is an insulin-sensitizing agent, seems to be the solution. Not only does metformin help reduce serum glucose, it could fix many of the primary pathophysiologic abnormalities, including lipid metabolism, endothelial function, and platelet hyperactivity for CVD in patients with diabetes mellitus.

A non-randomized, pair-matched cohort study evaluated the association between metformin and subsequent development of DVT using a nationwide, population-based database. The study cohort included 7,154 patients with type 2 diabetes who were on metformin therapy from 1997 to 2003. To compare the data, a 7,778 matched control cohort without metformin therapy was selected. The two groups were matched for age, sex, and comorbidities.

The results of this cohort analysis showed that out of 14,945 total patients (7,167 metformin therapy group vs. 7,778 control group) included in this study, 60 patients developed DVT during an average follow-up period of 3.74 years. Prevalence of DVT was seen in 16 (0.21%) patients on metformin therapy and 44 (0.56%) patients in the control group. Moreover, results of the Kaplan-Meier analysis showed that metformin therapy is associated with lower incidence of DVT (log-rank test, P = 0.001). There was a 0.427-fold (95% confidence interval 0.240-0.758; P = 0.004) risk reduction in DVT, unrelated to age, sex, and comorbidities, noted in patients on metformin therapy. This study suggested that metformin use may have protective effects against developing DVT in patients with type 2 diabetes.

The results of the new retrospective cohort study, led by William Hinton, MSc, from the University of Surrey, United Kingdom, confirm the previous findings. These results were recently presented at the Diabetes UK Professional Conference (DUPC) 2019.

In this study, research focused on assessing the occurrence of VTE in patients with type 1 and 2 diabetes, as well as in people without diabetes. Additionally, the effect of metformin on VTE in regard to several risk factors for type 2 diabetes was evaluated.

Data included in this cohort was pooled from 164 general practitioners’ practices and nearly 3 million patients in a nationally representative sample. All patients were selected based on medication, confirmatory glycemic measurements for diabetes such as HbA1c, and type of diabetes.

To determine the study objective, the incidence of VTE was calculated and stratified by diabetes type or no diabetes. Confounders, including age, gender, BMI, smoking history, CKD, atrial fibrillation, and HbA1c, were adjusted for. Additionally, treatment with aspirin, statins, metformin, SGLT2 inhibitors, and GLP-1 receptor agonists was considered.

The results of data analysis showed that the average age appeared to be 70 years for patients with type 2 diabetes, 44 for patients with type 1 diabetes, and 47 for patients without diabetes. Among patients with type 2 diabetes, 63% were on metformin versus 15% of patients with type 1 diabetes  therapy. Average HbA1c at the time of diagnosis for diabetes were 7.8% and 9.6% in type 2 and type 1, respectively. It was noted that 5.5% of patients with type 2 diabetes experienced VTE in comparison to 1.9% of patients with type 1 diabetes and 1.7% of patients without diabetes. Moreover, analysis showed that risk factors for prevalence of VTE are as follows: female gender [OR 1.22], active smokers [OR 1.24], CKD [OR 1.39], and atrial fibrillation [1.38].

Investigators of this study propose that metformin could decrease risk of VTE via reduction of platelet activation and/or improving endothelial function. However, this study did not find any association between HbA1c and VTE.

Practice Pearls:

  • Metformin could decrease risk of VTE via reduction of platelet activation and/or improving endothelial function.
  • There was a 0.427-fold (95% confidence interval 0.240-0.758; P = 0.004) risk reduction in DVT, unrelated to age, sex, and comorbidities, noted in patients on metformin therapy.
  • 5.5% of patients with diabetes experienced VTE in comparison to 1.9% of patients with type 1 diabetes and 1.7% of patients without diabetes.

References:

Lu, Dai-Yin et al. “Metformin use in patients with type 2 diabetes mellitus is associated with reduced risk of deep vein thrombosis: a non-randomized, pair-matched cohort study” BMC cardiovascular disorders vol. 14 187. 15 Dec. 2014, doi:10.1186/1471-2261-14-187

Type 2 Diabetes Ups Odds of VTE, Metformin Reduces It – Medscape – Mar 08, 2019.

Ghazal Blair, Pharm.D. Candidate 2019, LECOM School of Pharmacy