Simplify to Succeed: How Fixed-Dose Combination Therapies Improve Diabetes Adherence
Managing type 2 diabetes in patients with multiple comorbidities is often a balancing act. Advanced practice registered nurses (APRNs) must weigh clinical efficacy against treatment complexity, which can be a major barrier to medication adherence. For many patients, multiple daily pills, injections, and dosing schedules lead to missed doses, confusion, or even intentional discontinuation.
Fixed-dose combination (FDC) therapies offer a streamlined solution. By combining two or more agents into a single formulation, FDCs reduce pill burden and simplify care without sacrificing glycemic control or cardiometabolic benefit.
Complexity Breeds Non-Adherence in Diabetes
Numerous studies link complex medication regimens with poor adherence. One landmark study found that adherence increased from 59% with three-times-daily dosing to over 83% with once-daily regimens.¹ A meta-analysis confirmed that FDCs significantly improved medication compliance in patients with hypertension and dyslipidemia, which are common comorbidities in diabetes.²
More than 80% of adults with type 2 diabetes are also overweight or obese, and many have cardiovascular or renal complications.³ These patients are frequently prescribed multiple agents targeting multiple conditions. As complexity increases, adherence often declines, and clinical effectiveness may decline as well.
The Case for Fixed-Dose Combination (FDC) Therapies
FDCs combine two or more active pharmaceutical ingredients into a single dosage form, simplifying the regimen without compromising efficacy. In type 2 diabetes, common combinations include:
- Metformin + SGLT2 inhibitor (e.g., metformin/dapagliflozin)
- Metformin + DPP-4 inhibitor (e.g., metformin/sitagliptin)
- Basal insulin + GLP-1 receptor agonist (e.g., insulin glargine/lixisenatide)
These options are supported by the American Diabetes Association (ADA), which encourages simplification of therapy to improve adherence and clinical outcomes.⁴
Clinical Advantages: Adherence, Cost, and Outcomes
Why should APRNs consider FDCs for eligible patients?
- Improved adherence: Fewer pills increase the likelihood of consistent use.¹,²
- Lower copays: Many insurers classify FDCs as a single prescription, which can reduce out-of-pocket costs when there is one copay instead of two.⁵
- Simplified instructions: Beneficial for patients with limited health literacy, cognitive impairment, or complex regimens
- Reduced risk of therapeutic duplication: Simpler regimens may help avoid overlapping or conflicting therapies
- Earlier use of multi-mechanism therapy: Helps address clinical inertia by implementing combination treatment sooner
Although the up-front cost of FDCs may be higher, long-term savings from improved glycemic control and reduced complications support their use in value-based care.⁶ In cases where the FDC is a brand-name medication, patients may also benefit from cost-saving cards offered by the manufacturer.
What APRNs Should Consider Before Prescribing
Not every patient is an ideal candidate for an FDC. Key factors to evaluate include:
- Renal and hepatic function: These affect drug metabolism and clearance, particularly for metformin-containing combinations. Evaluate each drug in the FDC product to confirm it is the best choice for the patient.
- Dosing inflexibility: FDCs may limit the ability to adjust individual components.
- Insurance coverage: Copays and formulary status vary across plans.
- Component changes: If one ingredient needs to be discontinued or titrated independently, the FDC may need to be replaced with individual agents.
Counseling Tips to Maximize Adherence
When initiating FDC therapy, APRNs should:
- Explain the rationale: Emphasize how fewer pills can still achieve therapeutic targets.
- Review administration instructions: Clarify timing, storage, and whether to take with food.
- Discuss side effects: Address the safety profile of each active ingredient.
- Set expectations: Reassure patients that simplification is designed to improve their experience, not complicate it.
Patient understanding and engagement are crucial for adherence and long-term success.
Practical Takeaways for APRNs
Fixed-dose combination therapies are more than a matter of convenience. They represent a clinically sound strategy for reducing treatment burden, improving adherence, and enhancing outcomes in patients with type 2 diabetes.
As diabetes management evolves, APRNs are uniquely positioned to drive patient-centered approaches that emphasize both efficacy and simplicity. FDCs are one of the tools that make this possible.
References
- Eisen SA, Miller DK, Woodward RS, Spitznagel E, Przybeck TR. The effect of prescribed daily dose frequency on patient medication compliance. Arch Intern Med. 1990;150(9):1881–1884.
- Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med. 2007;120(8):713–719.
- Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2022. Atlanta, GA: US Department of Health and Human Services; 2022.
- American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2024;47(Suppl 1):S1–S308.
- Patel H, Bell DSH. Advantages of fixed-dose combination therapy in type 2 diabetes. Clin Diabetes. 2013;31(1):6–8.
- Polinski JM, Kim SC, Jiang D, et al. Impact of fixed-dose combination therapy on adherence and clinical outcomes: a systematic review. J Gen Intern Med. 2014;29(4):594–602.
