Adherence Gaps Persist Among Newly Diagnosed Patients with T2D

Nearly 75% of newly diagnosed patients with type 2 diabetes (T2D) fail to stay on track with combination therapy. Amid persistent gaps in medication adherence, age and insurance type may be driving more of that gap than previously recognized, according to JAPhA Pharmacotherapy.¹

“Although multiple clinical trials have demonstrated that intensive glycemic control reduces the risk of complications, it remains challenging to achieve long-term durable glycemic control in clinical practice,” wrote the authors of a study published in Endocrinology and Metabolism.² “This challenge stems from both the lack of fundamental therapies addressing progressive β-cell dysfunction and therapeutic inertia experienced by health care providers and patients.”

Approximately 71% of drug-naïve patients who initiate combination therapy for T2D fail to maintain adherence during their first year of treatment. This finding, derived from a retrospective study using a group-based trajectory model, highlights a significant gap between clinical trial efficacy and real-world outcomes.¹

READ MORE: GLP-1s Taking Over Indications Outside of Diabetes and Weight-Loss | APhA 2026

Although early intensive treatment is increasingly recognized as a way to achieve durable glycemic control, the complexity of multidrug regimens appears to be a double-edged sword for many newly diagnosed patients. Pharmacists are now at the forefront of addressing these adherence patterns, which the study categorized into 4 distinct trajectories: adherent, gradual decline, gaps in adherence, and rapid decline.^1,2

According to the American Diabetes Association (ADA), the clinical rationale for starting patients on multiple agents simultaneously is compelling, as experts argue that monotherapy is essentially a treat-to-fail approach that ignores the 8 major pathophysiologic defects of T2D. By utilizing combinations such as glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and pioglitazone, pharmacists can target issues like decreased insulin secretion and increased glucose reabsorption early in the course of patients’ disease.³

However, real-world data shows that only about 10% to 12% of drug-naïve patients currently receive this initial combination therapy, with a notable preference for loose-dose combinations over fixed-dose formats.⁴ Despite the benefits of rapid A_1C reduction and β-cell preservation highlighted in landmark trials like EDICT (NCT01107717) and VERIFY (NCT01528254), the transition from monotherapy to these intensive regimens remains a challenge for many.^1-3

The barriers to maintaining these regimens are multifaceted and often rooted in socioeconomic and systemic factors. For instance, patients enrolled in health maintenance organization (HMO) plans or those with more restrictive comprehensive coverage are significantly more likely to experience rapid declines in adherence compared with those involved with other plan types.^1,5

Age also serves as a major predictor, with younger patients between 18 and 34 years old exhibiting higher rates of nonadherence than their older counterparts.

Furthermore, limited health literacy remains a pervasive obstacle, as patients who struggle to understand complex medication instructions often experience unintentional nonadherence. These challenges are compounded by the high cost of combination therapies, which can reach $1300 per month compared with just $85 for sequential therapy.^1,3,5

Pharmacists are uniquely positioned to bridge these adherence gaps through targeted, personalized interventions. Scoping reviews suggest that pharmacist-led counseling, medication reviews, and the implementation of reminder tools can significantly improve behavior among patients with multimorbidity, according to Patient Preference and Adherence.⁶

Specifically, addressing misconceptions about drug safety and simplifying treatment regimens can mitigate the therapeutic inertia often seen in standard care, as Endocrinology and Metabolism authors explain.² Although some experts caution that combination therapy may preclude individualized assessment of side effects, pharmacists can provide the necessary follow-up to monitor these reactions while optimizing the efficacy of the regimen.^2,3,5,6

By focusing on modifiable factors like health literacy and communication, pharmacists can help transform a treat-to-fail trajectory into a pathway for long-term health and complication prevention.^1,5

“Policymakers and health care providers should focus on simplifying medication access, tailoring educational programs to younger populations, and mitigating administrative barriers associated with restrictive health plans,” concluded the authors of the current study.¹ “By addressing these challenges, adherence rates and overall health outcomes for patients with T2D can be improved, ultimately enhancing long-term patient outcomes.”

READ MORE: Diabetes Resource Center

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REFERENCES

1. Fatima B, Cheruvu SS, Ofili SC, et al. Adherence in initiators of combination therapy among drug-naïve patients with T2D: a real-world study using group-based trajectory model. JAPhA Pharmacother. 2025;3(1):100024. https://doi.org/10.1016/j.japhar.2025.100024

2. Kim JY, Kim NH. Initial combination therapy in T2D. Endocrinol Metab. 2023;39(1):23-32. https://doi.org/10.3803/EnM.2023.1816

3. Debate weighs the efficacy of initial combination therapy for T2D. ADA. July 18, 2023. Accessed April 10, 2026. https://www.adameetingnews.org/debate-weighs-the-efficacy-of-initial-combination-therapy-for-type-2-diabetes/

4. Majd Z, Chen H, Johnson ML, et al. Real-world treatment patterns in drug naïve T2D population: initial combination therapy vs. sequential step-therapy. JAPhA. 2024;65(1):102295. https://doi.org/10.1016/j.japh.2024.102295

5. Pourhabibi N, Mohebbi B, Sadeghi R, et al. Determinants of poor treatment adherence among patients with T2D and limited health literacy: a scoping review. J Diabetes Res. 2022 Jul 4;2022:2980250. doi: 10.1155/2022/2980250.

6. Sholihah S, Rahayu FP, Farhana L, et al. Pharmacist-led interventions to improve medication adherence among patients with multimorbidity: a scoping review. Patient Prefer Adherence. 2025 Nov 14;19:3589-3602. doi: 10.2147/PPA.S542881.