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Medication adherence in patients with type 2 diabetes: barriers & interventions

  • Globally around 462 million individuals are living with T2D while another 50% remain undiagnosed1,2.
  • Rate of non-adherence to diabetes medication and the lifestyle recommendations varies between 20-60%3.
  • Determinants for non-adherence include factors common to other chronic diseases in older age4,5.
  • Interventions in diabetes should be personalized and multidimensional to include more than one type of intervention5.

Patients suffering from symptom-less chronic diseases are susceptible to non-adherence behavior toward their medication and lifestyle recommendations, especially if they are associated with other comorbidities. Type-2 Diabetes (T2D) is a metabolic disorder and is frequently associated with other co-morbodities like obesity and hypertension. These patients are predisposed to develop cardiovascular diseases, diabetic retinopathy, diabetic neuropathy, chronic kidney disease (CKD), and non-alcoholic fatty liver disease (NAFLD)6,7.

Type 2 diabetes – a global pandemic

Type 2 diabetes has developed into a global pandemic. The increasing globalization hand-in-hand with growing urbanization has resulted in massive changes in people’s lifestyles and food habits. It has tipped the balance towards a high-caloric, sugar-rich, fat-laden diet with increasingly lower levels of physical activity8. As per the estimates, the global burden of T2D in 2017 was 462 million1, which is expected to reach 590 million by 20357 and 693 million by 20452. The current assessments of T2D prevalence are likely to be an underestimate, as approximately, half of the patients remain undiagnosed2. Unlike other typical age-associated diseases, T2D primarily affects middle age (40-60) and is also becoming increasingly common in children and young adults. Importantly, the disease burden is growing in middle-to low-income countries8,9 such that it is no longer considered a rich person’s disease but rather a raging global issue requiring collective attention. An equally attention-worthy issue is non-adherence to medication for T2D. Even though patients suffer from potentially life-threatening diseases, they are prone to non-adherence due to the chronic and symptom-less nature of the disease. Patients with T2D are required to take multiple pills per day owing to the associated co-morbidities further increasing the odds of medication non-adherence5.

T2D is a significant economic and healthcare burden

The worldwide total healthcare expenditure for diabetes and related ailments was pegged at USD 850 billion for the year 2017 and is set to rise to 958 billion by 2045. As per estimates, between 6-16% of the total healthcare budget is being spent on diabetic care globally1, which is only set to increase along with the rising incidence of the disease and the associated decline in overall health.

The T2D therapy involves altering diet, lifestyle changes, and increasing physical activity in addition to the prescribed pharmacological treatments. Several medications, both oral and injectables, are currently approved and marketed to address the two related pathological mechanisms of the disease – insulin insufficiency and insulin resistance7.

Diabetes and medication adherence

Both medications and healthy lifestyle recommendations are essential for the tight regulation of blood glycaemic levels – HB1Ac < ~7.0 % – which significantly helps in reducing both microvascular and macrovascular complications 10 Even though diabetes is associated with multiple comorbidities and a 2-3 fold higher risk of all-cause mortality11, diabetes medication adherence rates remains poor. Failure to adhere to anti-diabetics, healthy lifestyle, and dietary habits increases3,12:

  • Sub-optimal glycaemic control
  • Hospitalizations, medical consultations, and use of healthcare services
  • Diabetes-related complications and developing co-morbidities
  • Poor health and decline in quality of life
  • All-cause mortality
  • Healthcare costs3,12,13

Even moderate serum glycaemic control through improving medication adherence in diabetes and lifestyle changes can lead to better patient health and healthcare economics.

Diabetes medication adherence rates

On average about ~20-60% of patients are non-adherent to the prescribed medication in T2D3. Medication non-adherence is divided into two stages – initiation and persistence. Non-adherence at the initiation step, where patients do not initiate the prescription is called primary non-adherence, while failing to fill the subsequent prescriptions is called secondary non-adherence. Both these steps are key to achieving good glycaemic control. Several observational studies have reported on average 56.2% of patients to be persistent to oral anti-diabetic medication, while 31.4% of patients discontinued the medications5. Similarly, insurance claim data shows that only 55% of patients were persistent in subcutaneous insulin injections within the first year of therapy initiation5.

Table 1: Diabetes medication adherence statistics in different global regions.

Global regionsRate of adherence to T2D medication
High-income nations1338-93%
Middle East and North Africa1338-41%
Indian subcontinent1644-82%
High-income Asian countries1757.1%
African countries1640-80%

Adherence to lifestyle and dietary recommendations in T2D

All patients diagnosed with diabetes are required to follow a strict diet and maintain a healthy lifestyle with a reduction in sedentary habits and incorporating at least the recommended levels of physical activity in their daily routine. Following a healthy lifestyle and a balanced diet is pertinent for good glycaemic control and is recommended in addition to the pharmacological prescriptions. However, more often than not, patients fail to pay heed to this advice and do not eat a balanced diet or adopt exercise in their daily routine 5 Some studies have reported an adherence rate of 65% for the diet and 19% for exercise14.

Factors affecting medication adherence in diabetes

Non-adherence to medication can be an intentional or a non-intentional behavior. It can be present in different ways, patients not taking medicine on time, not taking all doses, lowering or exceeding the dosage, skipping certain medicines, and not taking the medicine exactly as prescribed. Non-adherence to anti-diabetic medication is a common scenario since T2D checks all the boxes that can cause lower adherence rates, such as16:

A. Chronic disease: The long-term nature of disease necessitates using lifelong medications that result in several issues contributing to non-adherence

  • Concerns about costs
  • Forgetfulness
  • Problem with persistence in long-term
  • Change in priorities

B. Symptom-less disease: Since it does not present visible or painful symptoms the necessity of taking medicine is not perceived and patients are not confronted with immediate consequences

  • Lower necessity vs concern beliefs
  • No immediate gains result in lower priority to the anti-diabetics

C. Associated co-morbidities: As noted above, diabetes is associated with high BMI, hypertension, cardiovascular disease, and microvascular diseases5.

  • Polypharmacy, the act of taking more than two pills, results in forgetfulness and mixing-up of medications.
  • Confusion due to the complexity of regimens, as medications are specified to be taken multiple times a day either with meal or post-meal
  • Poor mental health due to poor overall health

D. Side effects: Drug-related side effects are a key reason for the lower uptake of the medications. Anti-diabetic drugs are associated with adverse effects like weight gain, hypoglycemia, enhanced risk of colorectal cancer18

E. The challenge with injectibles: Injectible insulin is often prescribed once the first line of therapy is not sufficient to achieve the optimum glycaemic control. However, sub-cutaneous self-injections become an important factor in non-adherence since patients are either not comfortable with them or do not perform the action as advised resulting in suboptimal dosing. Among others, the frequency of these injections and specific timings for dosing also poses a unique challenge for adherence to insulin therapy in T2D5.

F. Older age or demographics: Older adults are reported to be more prone to non-adherence due to various issues as summarized in the following table. Since T2D is known to largely affect the elderly population, it becomes challenging.

Table 2: Factors affecting medication adherence in diabetes5:

Barrier to adherenceType of associated non-adherence
Lack of information or
disease understanding		Primary and intentional
Self-efficacyPrimary and non-intentional
Side effectsSecondary and intentional
Medication costsBoth primary and secondary; intentional
Complex dosingSecondary and non-intentional
Schedule disruptionSecondary and non-intentional
PolypharmacySecondary and non-intentional
Physical dexterityBoth primary and secondary
Access to pharmacySecondary and non-intentional
Health illitracyBoth primary and secondary plus non-intentional
Lack of patient engagementBoth rimary and secondary; intentional and non-intentional
Co-morbiditiesBoth primary and secondary; non-intentional

Improving medication adherence in diabetes

Addressing the prevalent non-adherence behavior in diabetic patients requires two major steps: 1) Assessment and identification of non-adherence behavior; 2) Administering optimal interventions to alleviate non-adherence

A. Identifying non-adherence

Identification of non-adherence is the first step towards addressing this issue, which calls for effective approaches for its measurement. However, there is no established gold standard for effectively measuring adherence. For more on this, see our article Measuring adherence – an “Achilles heel” in medication adherence. Body fluid assays, pill counts, pharmacy refill records, and self-reporting instruments like the Morisky Scale, TABS, and MAR-scale have all been utilized widely in T2D. However, each method has limits, and a combination is frequently required to obtain a more realistic image15.

B. Interventions to improve medication adherence in diabetes

Various strategies and interventions have been employed to address non-adherence in T2D. Some of the selected strategies are described below5.

  • Shared decision-making: It is a highly recommended strategy that includes four constructs – establishing a relationship between patient and provider, exchange of information about the disease, risk factors, and available treatments, deliberation on different options, and finally arriving at a decision agreed upon by everyone.
  • Polypill: Polypharmacy (use of ≥ 5 pills) is common in T2D patients due to associated comorbidities and is a major cause of non-adherence. The complexity of the regimen, increased side effects due to drug interactions, and simply the act of taking multiple pills overwhelm patients. Polypills that combine several drugs in one pill could address this issue. Advances in the field may lead to the availability of personalized polypills that could substantially tackle this challenge.
  • Educational interventions: A personalized approach towards educating patients and increasing health literacy, consequences of non-adherence, and ways to tackle it, is required. It should depend upon the patient’s cognitive and functional status, patients treatment goals, cultural and health beliefs plus attitude toward medication.
  • Mobile health apps: Mobile applications can assist, remind and monitor the medication uptake and are helpful to address non-intentional non-adherence. For more on this please read our article – Mobile apps for enhancing adherence to chronic diseases
  • Behavioral interventions: Social cognitive theory-based interventions are used to address non-adherence in T2D. To learn more, please read our article – Methods of behavior change in medication non-adherence

Conclusion

As the world population is aging progressively, diseases that affect the elderly and require lifelong treatment are a major concern and an economic burden. Type-2 diabetes majorly affects middle-aged to older adults and significantly lowers their quality of life and life expectancy. It can be effectively controlled by making simple changes in lifestyle and adhering to medications. However, treatment success in T2D is compromised by poor diabetes medication adherence rates. Improving medication adherence in diabetes require a combination of educational and behavioral interventions as well as the use of new-age pharmacological approaches5.

References

1.  Cho NH, Shaw JE, Karuranga S, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. Apr 2018;138:271-281. doi:10.1016/j.diabres.2018.02.023

2.  Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes – Global Burden of Disease and Forecasted Trends. J Epidemiol Glob Health. Mar 2020;10(1):107-111. doi:10.2991/jegh.k.191028.001

3.  Huang J, Ding S, Xiong S, Liu Z. Medication Adherence and Associated Factors in Patients With Type 2 Diabetes: A Structural Equation Model. Front Public Health. 2021;9:730845. doi:10.3389/fpubh.2021.730845

4.  Jyotiranjan Sahoo, Sambedana Mohanty, Arijit Kundu, Venkatarao Epari. Medication Adherence Among Patients of Type II Diabetes Mellitus and Its Associated Risk Factors: A Cross-Sectional Study in a Tertiary Care Hospital of Eastern India. Cureus. 2022 Dec 29;14(12):e33074. doi: 10.7759/cureus.33074

5.  Swe K, Reddy SSK. Improving Adherence in Type 2 Diabetes. Clin Geriatr Med. Aug 2020;36(3):477-489. doi:10.1016/j.cger.2020.04.007

6.  Iglay K, Hannachi H, Joseph Howie P, et al. Prevalence and co-prevalence of comorbidities among patients with type 2 diabetes mellitus. Curr Med Res Opin. Jul 2016;32(7):1243-52. doi:10.1185/03007995.2016.1168291

7.  Reed J, Bain S, Kanamarlapudi V. A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives. Diabetes Metab Syndr Obes. 2021;14:3567-3602. doi:10.2147/DMSO.S319895

8.  Seuring T, Archangelidi O, Suhrcke M. The Economic Costs of Type 2 Diabetes: A Global Systematic Review. Pharmacoeconomics. Aug 2015;33(8):811-31. doi:10.1007/s40273-015-0268-9

9.  Galicia-Garcia U, Benito-Vicente A, Jebari S, et al. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. Aug 30 2020;21(17)doi:10.3390/ijms21176275

10.       Hutchins V, Zhang B, Fleurence RL, Krishnarajah G, Graham J. A systematic review of adherence, treatment satisfaction and costs, in fixed-dose combination regimens in type 2 diabetes. Curr Med Res Opin. Jun 2011;27(6):1157-68. doi:10.1185/03007995.2011.570745

11.       Lin X, Xu Y, Pan X, et al. Global, regional, and national burden and trend of diabetes in 195 countries and territories: an analysis from 1990 to 2025. Sci Rep. Sep 8 2020;10(1):14790. doi:10.1038/s41598-020-71908-9

12.       Onwuchuluba EE, Oyetunde OO, Soremekun RO. Medication Adherence in Type 2 Diabetes Mellitus: A Qualitative Exploration of Barriers and Facilitators From Socioecological Perspectives. J Patient Exp. 2021;8:23743735211034338. doi:10.1177/23743735211034338

13.       Wibowo M, Yasin NM, Kristina SA, Prabandari YS. Exploring of Determinants Factors of Anti-Diabetic Medication Adherence in Several Regions of Asia – A Systematic Review. Patient Prefer Adherence. 2022;16:197-215. doi:10.2147/PPA.S347079

14.       Delamater AM. Improving patient adherence. Clinical Diabetes. 2006;24(2):71-77. doi:doi.org/10.2337/diaclin.24.2.71

15.       Gonzalez JS, Schneider HE, Wexler DJ, et al. Validity of medication adherence self-reports in adults with type 2 diabetes. Diabetes Care. Apr 2013;36(4):831-7. doi:10.2337/dc12-0410

16. Omer Q. B. Al-lela RAA, Lawan AL-Mufti, Nojdar Kamal, Siber Qasim, Rahma Sagvan, Zaynab Hinir, Hawjeen khidr. Medication Adherence Among Diabetic Patients in Developing Countries: Review of Studies. Sys Rev Pharm. 2020;11(8):270-275.

17. Lee C S, Tan J H M, Sankari U, Yi, Koh L E, Tan N C. Assessing oral medication adherence among patients with type 2 diabetes mellitus treated with polytherapy in a developed Asian community: a cross-sectional study. BMJ Open. 2017 Sep 14;7(9):e016317. doi: 10.1136/bmjopen-2017-016317

18. Lee D S, Lee H. Adherence and persistence rates of major antidiabetic medications: a review. Diabetology & Metabolic Syndrome. 2022; 14:12. https://doi.org/10.1186/s13098-022-00785-1