Introduction

Patients with type-2 diabetes mellitus (T2DM) frequently have poor glycemic control [fasting blood glucose (FBG) >152 mg/dL, comparable to glycated hemoglobin (HbA1c): 7%], despite the availability of various antihyperglycemic agents and evidence-based treatment guidelines for optimal glycemic control. Delay in treatment intensification (TI; delay in the escalation of treatment plans for T2DM patients who fail to attain ideal glycemic control) critically contributes towards poor glycemic control. Delay in treatment intensification has been linked to prolonged hyperglycemia, increased risk of diabetes complications, reduced quality of life (QoL), and higher glucose toxicity. Therapeutic ineffectiveness due to delayed TI hinders the management of hyperglycemia. Optimizing the diabetes management is essential to reduce the burden of diabetes-associated complications.

Aim

To determine the clinical impact, prevalence and associated determinants of delayed TI, in T2DM patients.

Patient Profile

• Adult T2DM patients treated with antidiabetic medications (for ≥ 3 months) and attending follow-up visits at University of Gondar Comprehensive Specialised Hospital (UoGCSH) in Northwest Ethiopia (2018-2024). 
• The study population had an FBG > 152 mg/dL.

Methods

Study Design

Outcomes

Dependant Variables

Independent variables

• Patient-related variables: Age, gender, income, duration of DM, comorbidities, financial constraints, lack of awareness and treatment non-adherence.
• Healthcare provider-related variables: Fear of polypharmacy effect on adherence, lack of familiarity with guidelines, specialty of doctors, lack of team-based care, lack of information on new treatment options, fear of potential risks of hypoglycaemia, lack of training, professionals’ negligence and fatigue.
• Various healthcare-system-related factors

Operational Definitions

• Index date: The first date when the FBG measurement exceeded 152 mg/dL following the initiation of antidiabetic treatment.
• Poor glycemic control: FBG >152 mg/dL, corresponding to an HbA1c of 7% as per the American Diabetes Association (ADA) criteria. This study utilized FBG as the follow-up tool due to the inconsistent availability of HbA1c data during patient diagnosis and monitoring.
• Short duration: Diabetes duration less than 5 years.
• Long duration: Diabetes duration ≥5 years.
• Incomplete record: If important data such as FBG and date of diabetes diagnostic care were not recorded.
• Fasting: No caloric intake for ≥8 hours.
• Comorbidities: Patients with T2DM and other chronic medical or psychiatric disorders.
• Comorbidities score: Mild, Charlson’s comorbidity index (CCI) scores of 1–2; moderate, CCI scores of 3–4 and severe, CCI score >5.
• Time to TI (TTTI): Calculated by subtracting the index date from the first date of TI.
• Early intensifiers: Those intensifying the treatment within 6 months after the index date.
• Delayed intensifiers: Those intensifying more than 6 months after the index date.
• Chronic diabetic complications: A patient with diabetes and at least one confirmed macrovascular complication (diabetic-related cardiovascular disease, peripheral vascular disease and stroke) or microvascular complications (including diabetic nephropathy, diabetic retinopathy, peripheral neuropathy and others), after being diagnosed with diabetes.

Results

• The study population comprised of 420 T2DM patients with poor glycemic control (FBG >152 mg/dL) following initiation of antidiabetic medication. 
• Median age of the study population was 55 years, 53.3% were females, and 75% of them were urban residents. Nearly 57.6% of the study population had a diabetes duration of ≥ 5 years. 
• Most patients (75%), were treated with metformin monotherapy at the index date, the remainder one-fourth of the study population received insulin or other oral antidiabetics (OADs), either as monotherapy or in combination (metformin+glibenclamide).
• Of the entire study population, 32.6% were being treated with cardioprotective medications. 
• Of the entire study population, 48.6% (n=204) received early TI, the remainder 51.4% (n=216) experienced delayed TI [a median delay of 14 months (IQR: 7.5–42 months) from the index date]. Of these: 48.2% (n=104) had no insulin initiation, 31.5% (n=68) did not receive a second OAD, 19.4% (n=42) had no dose adjustment and 0.9% (n=2) had no modification in the frequency of medication administration. 
• For patients who received early TI, the median time to TI was 1 month (IQR: 1–2.04) after the index date. A Mann-Whitney U test yielding a Z value of 17.821 (p<0.001) indicated a strong association between delayed TI and prolonged time to intervention, thus highlighting the need for timely treatment adjustments in diabetes management.
• A higher proportion of patients experiencing delayed TI developed at least one new chronic diabetic complication, as compared to those receiving early TI (43.1% vs. 23.5%) (Fig. 1). The patents with delayed TI had 2.28-fold higher odds of developing complications vs. those with early TI [odds ratio (OR): 2.28; 95% confidence interval (CI): 1.48 to 3.53].

Fig. 1: Incidence of diabetes-associated complications in the study groups

• The most prevalent chronic diabetic complications that occurred in the delayed TI group included retinopathy (18.1%), neuropathy (14.4%) and nephropathy (6.0%). Other complications like hypertension, stroke, heart failure and diabetic foot ulcer were seen in 4.64% of the cases. 
• Longer duration (≥ 5 years) of diabetes [adjusted ORs (AOR): 1.68; 95% CI 1.13 to 2.5; p=0.011), presence of comorbidities (AOR 1.83; 95% CI 1.04 to 3.2; p=0.035) and use of cardioprotective medications (AOR 1.59; 95% CI: 1.04 to 2.43; p=0.033) were identified as significant predictors of delayed TI. 
• The patient-related variables contributing towards delayed TI included financial limitations, insufficient patient awareness about disease and treatment, negative beliefs, fear of injections and non-adherence to treatment. 
• The healthcare provider-related factors associated with delayed TI included professional fatigue and knowledge gaps. The health system-related factors such as inadequate healthcare infrastructure and limited access to structured health education also contributed towards delayed TI.

Conclusions

• There is a high prevalence of delayed TI in T2DM patients. Various factors such as comorbidities, longer disease duration, low patient awareness, use of cardioprotective drug and various barriers related to the health-system and health-providers contributed substantially towards the delayed TI. 
• Improving on patient education, scheduling regular reviews for high-risk patients and improving clinical decision support tools for timely TI may help in early TI.
• Enhancing healthcare infrastructure, such as medication supply and diagnostic services, and offering refresher training to reduce provider fatigue, would also have a critical role in improving the delivery of diabetes care.

BMJ Open. 2025;15:e105455. doi:10.1136/bmjopen-2025-105455.