Cardiovascular disease leads to a new algorithm for diabetes treatment
Valentina Rodriguez1, Matthew C Weiss2, Howard Weintraub2
1Division of Endocrinology, Diabetes, and Metabolism, New York University School of Medicine, New York, NY, USA.
Insights
Diabetes medications impact cardiovascular disease (CVD) and heart failure (HF) risk differently. Newer agents show CVD benefits beyond glucose control, suggesting a shift in treatment strategy is needed for type 2 diabetes patients.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Patients with diabetes mellitus face elevated risks of atherosclerotic cardiovascular disease (CVD) and heart failure (HF).
- Traditional lipid-lowering therapies have not fully mitigated these risks.
- Previous diabetes treatments showed mixed results regarding CVD benefits, with some classes like thiazolidinediones even increasing HF risk.
Purpose of the Study:
- To review clinical trials examining the effects of diabetes treatments on plasma lipoproteins and cardiovascular outcomes.
- To evaluate the cardiovascular safety and efficacy of various diabetes medications.
- To propose a revised treatment algorithm for type 2 diabetes focusing on cardiometabolic effects rather than solely glycemic control.
Main Methods:
- Systematic review of clinical trials on diabetes mellitus treatments.
- Analysis of effects on circulating plasma lipoproteins, cardiovascular disease (CVD), and heart failure (HF).
- Evaluation of recent studies mandated by regulatory bodies for safety and efficacy data.
Main Results:
- Several earlier diabetes therapies lacked clear CVD benefits.
- Triglyceride-reducing agents did not demonstrate overall CVD reduction in prior trials.
- Newer agents like empagliflozin, canagliflozin, liraglutide, and semaglutide show CVD risk reduction.
- Pioglitazone demonstrated protective vascular effects in insulin-resistant patients.
- Observed benefits are likely due to cardiometabolic effects, not improved lipoprotein profiles.
Conclusions:
- Cardiovascular outcomes of diabetes medications vary significantly.
- Current treatment selection should consider cardiometabolic effects and patient risk for CVD and HF.
- A paradigm shift from solely HbA1c-focused therapy to a risk-stratified approach is recommended for type 2 diabetes management.
Abstract:
Patients with diabetes mellitus have increased rates of atherosclerotic cardiovascular disease (CVD) and heart failure (HF). This increase occurs despite optimal lipid-lowering therapies. We reviewed clinical trials of diabetes treatments and their effects on circulating plasma lipoproteins and CVD. Several earlier studies failed to demonstrate clear CVD benefit from diabetes therapies. In addition, triglyceride-reducing agents did not reduce overall CVD in large clinical trials although these trials were not conducted in cohorts selected as hypertriglyceridemic. Specific classes such as the thiazolidinediones increased HF. After Food and Drug Administration mandates for more rigorous safety data, recent studies have not only demonstrated CVD safety for many diabetes mellitus agents, but have also shown that certain newer medications such as empagliflozin, canagliflozin, liraglutide, and semaglutide reduce CVD. Moreover, pioglitazone use in insulin-resistant patients has resulted in decreased cerebrovascular and cardiovascular events, suggesting a protective vascular effect of this agent. Benefits from these newer classes of medications are unlikely to be because of improved lipoprotein profiles. These disparities in diabetes medication effects on CVD are likely attributable to each drug or drug class' cardiometabolic effects. Selecting medications based solely on their potential to lower hemoglobin A1C is an outdated therapeutic approach. We propose a new algorithm for treatment of patients with type II diabetes such that medication selection is based on the presence or risk of coronary artery disease and/or HF.
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