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How Cost and Formulation Affect Patient Adherence to Metformin Therapy 

Sep 15, 2020
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Stephen Rubano, PharmD. Candidate, USF Taneja College of Pharmacy 

Understanding factors that affect patient metformin adherence is essential, as improving medication adherence can reduce healthcare expenditures while producing healthier patients.  

Understanding the barriers to adherence is an essential step in treating patients. Many questions should be answered before choosing an appropriate therapy, such as: Is the patient committed to taking the medication three times daily? Can the patient afford the medication? Is there a cheaper option? Finding a balance between cost and convenience can be integral to success. Previous studies have attempted to measure the magnitude of such factors on patient adherence. A retrospective study, including over 10,000 participants, showed that simply changing the metformin formulation from immediate-release (IR) to extended-release (ER) formulations improved adherence by 8%. Although it’s difficult to translate the clinical impacts of these results, improvements in adherence have real implications in reducing healthcare spending for both insurer and patient.  


Recently, a study was published examining the effects of cost and formulation in treating patients with type 2 diabetes (T2D). Researchers performed a retrospective cohort study, including only patients receiving an initial therapy of either IR or ER metformin, no previous anti-diabetic medication, and a T2D diagnosis. Data were retrieved and analyzed from commercial insurance providers or Medicare over four years, adjusting for covariates such as age, sex, and out-of-pocket expense. The primary outcome for the study was termed “persistence,” defined as at least one metformin prescription claim within the 6-12-month period following the initial prescription. Secondary outcomes included adherence, measured by the number of prescriptions filled compared to a standard number of prescriptions required for sufficient metformin treatment. A total of 81,406 participants were included, with nearly 80% of individuals having commercial insurance. Univariate statistics were used to describe persistence and adherence between cost and formulation as odds ratios. 

The study concluded that patients taking ER metformin scored 13% higher in persistence and 2% higher in adherence than those taking IR formulations. The odds ratio comparing persistence for ER formulations was calculated to be 1.14 (95% CI 1.10 – 1.18, < 0.001). Although a modest increase, the results suggest that a simple change from IR to ER formulation can increase metformin adherence in patients with T2D. Additionally, odds ratios declined as the average metformin out-of-pocket price increased, indicating that the direct cost to consumers can influence persistence and adherence. Other studies have shown that implementing programs to lower patient co-pays can improve adherence by up to 5%. 

Interestingly, despite ER formulations traditionally being more expensive than their IR counterparts, patients on ER metformin displayed better adherence rates. Improvements in adherence could be explained by fewer gastric side effects or less frequent dosing. These findings suggest that patients value both cost and convenience in continuing therapy.  

Although the study illustrates improvements in adherence within patients taking ER metformin, it does not prove causality. A significant limitation of the study is the use of claims data for filled prescriptions as a measurement of persistence and adherence. Such data only reflects that the patients filled their prescriptions, and is not an accurate measure of adherence. Highlighted is the need for prospective studies better designed to analyze these relationships. With more robust evidence, the routine initial use of ER metformin may serve as a simple intervention for improving adherence. Because the population studied consisted of newly diagnosed patients, participants had simple regimens of metformin monotherapy with few comorbidities. A similar study using a population comprised of advanced patients on more complex anti-hyperglycemic regimens may offer a higher level of generalizability when considering the effects of medication cost and formulation on adherence.   

Practice Pearls: 

  • Increased patient costs are associated with poorer medication adherence in patients with type 2 diabetes. 
  • Study shows that patients taking ER metformin formulations have better adherence rates than those taking IR formulations (OR = 1.14, < 0.001) 
  • Evidence from the study suggests finding new methods for reducing medication costs, and side effects can have positive effects on health outcomes for patients.   


Flory, James H., and Alvin I. Mushlin. “Effect of Cost and Formulation on Persistence and Adherence to Initial Metformin Therapy for Type 2 Diabetes.” Diabetes Care, vol. 43, no. 6, 2020, pp. e66–67. doi:10.2337/dc19-2426.  

McQueen, R. Brett. “Capsule Commentary on Duru et al., Adherence to Metformin, Statins, and ACE/ARBs Within the Diabetes Health Plan (DHP).” Journal of General Internal Medicine, vol. 30, no. 11, 2015, p. 1697. doi:10.1007/s11606-015-3296-4.  

Donnelly, L. A., et al. “Adherence in Patients Transferred from Immediate-Release Metformin to a Sustained Release Formulation: A Population-Based Study.” Diabetes, Obesity, and Metabolism vol. 11, no. 4, 2009, pp. 338–42. doi:10.1111/j.1463-1326.2008.00973.x. 


Stephen Rubano, PharmD. Candidate, USF Taneja College of Pharmacy



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