Ineffective Cholesterol Treatment in Type 2 Patients

Addressing the gaps in lipoprotein cholesterol (LDL-C) control and statin prescribing among patients with type 2 diabetes.

Dyslipidemia is a significant adverse effect commonly associated with diabetes, even in patients with unremarkable lipid profiles. In addition, it is a significant risk factor of premature atherosclerotic cardiovascular disease, particularly coronary heart disease (CHD) and peripheral arterial disease. Although more recent studies have revealed a less pronounced effect, most authorities believe diabetes to carry at least a twofold increased risk, even when other conventional risk factors are taken into account.

People with type 2 diabetes (T2D) are at an increased cardiovascular risk many years before the onset of biochemical hyperglycemia and disease. Obesity and insulin resistance are common during this time, along with hypertension and dyslipidemia, which is referred to as a metabolic syndrome. These risk factors may play a significant role in the early development of CHD and the increased incidence of diabetes after a cardiovascular disease diagnosis. Current guidelines recommend screening and treating CVD risk factors in people with T2D. Administering 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) to type 2 diabetes patients has been shown to reduce the incidence of adverse CVD events by 23–33% regardless of their low-density lipoprotein cholesterol (LDL-C) levels or past CVD history. Even though statins have been proven to reduce CVD-related events and all-cause mortality, underutilization of statins in patients with T2DM has been reported in the form of inappropriate dosing, discontinuation, and adherence issues.

A recent retrospective cohort study in Finland aimed at investigating the gaps in lipoprotein cholesterol (LDL-C) control and statin prescribing among patients with type 2 diabetes (T2D) suggested that there are significant differences between low-density lipoprotein cholesterol (LDL-C) trajectories regarding LDL-C development, measurement activity, and statin treatment in patients with type 2 diabetes (T2D), concluding that many patients with T2D do not receive appropriate cholesterol-lowering treatment.

A total of 8592 T2D patients (53.8% males; 46.2% women) who had a disease duration of fewer than eight years were included in the study. 15.1% of men and 13.5% of women died during the follow-up. At baseline, on average, 66 year old males, 69 year old women; 60% and 56% were receiving a statin, respectively. Women achieved an LDL-C treatment target of < 2.5 mmol/L compared to men (50.8% vs. 55.7%, respectively; P < .001).  Four LDL-C trajectory were identified each with different statin treatment: “moderate-stable” (85.9%), “high-stable” (7.7%), “decreasing” (3.8%), and “increasing” (2.5%). Women had worse LDL-C control, were less often prescribed statin, or had it prescribed at a lower intensity, and exhibited treatment discontinuations more often than men.

No sex disparities were observed regarding measurement rates and overall measurement frequency. Women belonged more often to the “high-stable” LDL-C trajectory and less often to the “moderate-stable” LDL-C trajectory than men. Most patients (86%) had relatively stable LDL-C values around 2.3 mmol/L. The second-largest group (8%) consisted of patients with significantly “high-stable” LDL-C levels of around 3.9 mmol/L. Overall, clinically significant improvements in LDL-C levels were associated with statin treatment intensification, resulting in achieving LDL-C target rates of < 2.5 mmol/L and < 1.8 mmol/L of 66% and 30% for men, respectively, and 58% and 22% for women, respectively after the follow-up period. Overall, women had less LDL-C control, were prescribed statin at lower rates or lower intensity, and showed more frequent treatment discontinuations compared to men. Gender differences in statin dosages, adherence, pathophysiology, or pharmacodynamics could explain these findings. Thyroid diseases are also associated with higher LDL-C levels and are more common in women with T2D than men.

Practice Pearls:

• Statins are effective for primary or secondary CVD prevention, which is a leading cause of morbidity and mortality among T2DM patients.
• Many T2D patients do not receive adequate cholesterol-lowering treatment.
• Women often had less LDL-C control, were prescribed statin at lower rates or lower intensity, and showed more frequent treatment discontinuations than men.

Inglin, Laura, et al. “LDL-Cholesterol Trajectories and Statin Treatment in Finnish Type Diabetes Patients: A Growth Mixture Model.” Scientific Reports

Jialal, Ishwarlal, and Gurdeep Singh. “Management of diabetic dyslipidemia: An update.” World Journal of Diabetes

Elnaem MH, Mohamed MHN, Huri HZ, Azarisman SM, Elkalmi RM. Statin Therapy Prescribing for Patients with Type 2 Diabetes Mellitus: A Review of Current Evidence and Challenges. J Pharm Bioallied Sci.

Elmoataz Elmamoun PharmD Candidate, 2022, South College School of Pharmacy