Evaluation of CVD/CKD Risks in Patients with Type 2 Diabetes

Despite being on first-line oral anti-diabetic drug therapy, the risk of developing CVD/CKD in patients with type 2 diabetes remains high.

Patients with type 2 diabetes (T2D) are at higher risk for developing other complications, including but not limited to cardiovascular diseases (for example, myocardial infarction, heart failure, stroke, transient ischemic attack, peripheral artery disease, or carotid stenosis) and renal diseases (for example, chronic kidney disease or proteinuria). Consequently, they incur higher healthcare expenditures and have higher mortality risks. However, the information regarding the temporal development of CVD/CKD in patients diagnosed with T2D, despite being on first-line oral anti-diabetic therapy, is scant.

The study in this discussion is a retrospective, observational cohort study reviewing data of 1,286,287 patients with T2D from 2009 to 2018 to evaluate the association between T2D and the development of CVD and CKD and their impact on healthcare resources utilization (HCRU). The authors utilized the IBM MarketScan database to filter eligible patients from US commercial insurance, Medicare supplemental insurance, and Medicaid multistate databases based on the ICD-9-CM and ICD-10-CM diagnosis codes. Eligible patients include adult patients with confirmatory type 2 diagnosis who had a prescription for first-line oral anti-diabetic drug therapy. Patients were tracked from the date of their first oral anti-diabetic prescription (index date) to the end of continuous enrollment with the primary objective of determining the rate of incident diagnosis of CVD/CKD among patients with T2D who did not have CVD/CKD at the time of oral anti-diabetic initiation. Secondary objectives evaluated the temporal development of CVD and renal disease, as indicated by the time to the first incident diagnosis of CVD/CKD after the index date, the risk of incident of heart failure (HF) among patients with T2D and CKD, the risk of incident of CKD among patients with T2D and HF, and the HCRU cost for pre-incident and post-incident diagnosis of CVD/CKD. The author utilized descriptive statistics and cumulative incidence estimate to assess the primary objective and used the Cox proportional-hazards regression models to evaluate the time to an incident of HF or CKD diagnosis.

For the results, 16% of patients had an incident diagnosis of CVD or CKD in the median time of 297 days (IQR: 98 to 725). The most common first single diagnosis was CKD (7.9%), followed by peripheral artery disease (3.51%) and HF (2.58%). Besides, 10.34% of patients had an incident diagnosis of a cardiorenal outcome during the follow-up period, defined as the first diagnosis with both CKD and HF. After the first diagnosis of CKD, the risk for the HF was almost three times higher than patients without CKD (HR 2.92; 95% CI 2.85 to 2.99; p < 0.001). Similarly, after the first diagnosis of HF, the risk for CKD development was three times higher than patients with HF (HR 3.03; 95% CI 2.96 to 3.10; p < 0.001). Additionally, the elderly and patients with hypertension at baseline have a significantly higher risk of CKD and HF (p < 0.001). An incident diagnosis of CVD/CKD increased the annualized total costs per patient by 75%, mainly driven by increased medical costs (+90%) than pharmacy costs (+17%). 

Consistently with the worldwide data, progression to CVD/CKD is expected in patients with T2D despite being placed on first-line oral anti-diabetic therapy. In addition, economic burden and healthcare costs are significantly higher in association with the development of CVD/CKD. One of the limitations of this study is that it was not designed to compare different oral antibiotic types. However, even in the most recent ADA guideline for the management of diabetes, the first-line oral therapy for T2D is metformin. Of note, only 12% of the patients in the study received escalation of therapy with an SGLT2 inhibitor or GLP-1 RA after the index date. Recent studies have demonstrated the benefits of reducing cardiovascular risks and renal events with the addition of SGLT2 inhibitors or GLP-1 RAs. For example, the REWIND trial had demonstrated the benefit of dulaglutide, a GLP-1 RA, in preventing cardiovascular and renal outcomes in patients with T2D. However, can we ensure that most if not all at-risk patients are on appropriate and propitious drug therapy?

Practice Pearls

• CVD and CKD are common complications in patients with type 2 diabetes, despite being on a first-line oral anti-diabetic agent, and are associated with higher morbidity, mortality, and healthcare costs.
• Newer anti-diabetic agents such as SGLT-2 inhibitors and GLP-1 RAs provide benefits in preventing the cardiorenal outcome.
• Identifying at-risk populations and recommending appropriate treatments are essential in preventing CVD/CKD complications in type 2 diabetes.

Olufade, Temitope, et al. “Cardiovascular and renal disease manifestation and healthcare resource utilization in patients on first-line oral therapy for type 2 diabetes: A claims-based observational cohort study.” Diabetes, obesity & metabolism. 17 Aug. 2021.

Gerstein, Hertzel C et al. “Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomized placebo-controlled trial.” Lancet (London, England) vol. 394,10193 (2019): 121-130.

American Diabetes Association. “9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2021.” Diabetes care vol. 44,Suppl 1 (2021): S111-S124.

Ding Nguyen, PharmD Candidate, University of South Florida Taneja College of Pharmacy