In the United States, primary care providers (PCPs) manage over 75% of patients with type 2 diabetes (T2D). Thus, PCPs are uniquely positioned to improve the glycemic control and cardiometabolic health of patients with T2D. In recent years, emerging data on the role of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists in glycemic management and cardiorenal risk reduction has shifted the landscape of diabetes management from glucocentric to a concurrent focus on glucose management and cardiometabolic risk.
Moreover, recent updates to the American Diabetes Association's Standards of Care in Diabetes guideline, particularly those related to the use of SGLT2 inhibitors and GLP-1 receptor agonists, require PCPs to reframe approaches to diabetes pharmacotherapy and educate patients on the importance of managing cardiorenal and metabolic risk in addition to glucose levels. Given that PCPs are on the front lines of treatment of this disease, it is more important than ever that they remain up-to-date on the latest recommendations as they evolve their practice to help patients improve their cardiometabolic health. Here, we look at this new approach to T2D management in primary care.
A Paradigm Shift in Diabetes Management
The new paradigm of diabetes management emphasizes cardiorenal risk reduction and weight management in addition to focusing on glucose control and the prevention and management of microvascular and macrovascular complications with non–glucose lowering agents. While non–glucose lowering agents such as statins and angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have long been prescribed for prevention and risk reduction of cardiorenal disease, evidence-driven changes to the Standards of Care in Diabetes now call for the prescribing of diabetes medications to manage cardiorenal risk regardless of glycemic control. SGLT2 inhibitors are recommended first-line medications for T2D patients with heart failure (both with preserved and reduced ejection fraction) and chronic kidney disease. Similarly, for patients with atherosclerotic cardiovascular disease (ASCVD) or at risk for ASCVD, either a GLP-1 receptor agonist or a SGLT2 inhibitor with proven cardiovascular benefit is recommended. For patients with indications for both GLP-1 receptor agonists and SGLT2 inhibitors, the addition of the alternate medication is indicated if additional glycemic control or risk-factor reduction is needed. These recommendations are updated annually in the American Diabetes Association's Standards of Care in Diabetes, which summarizes evidence-based guidelines for comprehensive management of diabetes, cardiometabolic risk, and diabetes-related complications, including an abridged version for PCPs that also highlights key updates each year.
In 2008, the US Food and Drug Administration (FDA) mandated that all new glucose-lowering therapies have long-term cardiovascular outcome trials providing evidence to exclude an increased risk for major adverse cardiovascular events. Since then, multiple trials have shown both glycemic efficacy and cardiovascular safety of dipeptidyl peptidase (DPP-4) inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists. An unexpected finding in these trials was that many SGLT2 inhibitors and GLP-1 receptor agonists demonstrated cardiovascular benefit. Subsequent studies have demonstrated consistent benefits in heart failure, coronary artery disease, and chronic kidney disease, transforming the PCP's strategy to diabetes management.
A New Approach to Pharmacotherapy
The unexpected cardiovascular benefits of SGLT2 inhibitors and GLP-1 receptor agonists are also reframing approaches to diabetes pharmacotherapy. For decades, diabetes management has been glucocentric with a primary goal of achieving glycemic control measured by A1c. In this paradigm, metformin is the most common first-line medication, with additional agents added, as needed, to achieve glycemic targets. Once glycemic control is achieved, there is no indication to further intensify diabetes management. This approach to glucose control, along with the screening and management of microvascular complications and the treatment of hypertension and cholesterol to guideline-recommended levels to decrease risk for macrovascular complications, has been the cornerstone of diabetes management for decades. Diabetes quality measures that drive clinical care through pay-for-performance initiatives and educate patients about their glycemic control and risk for complications have further reinforced this approach.
Prescribing a diabetes medication when a patient's glycemic control is "at target" requires significant cognitive reframing for PCPs in how they manage the disease and engage patients in therapeutic decisions. Making this leap may not be as challenging as it seems, however. A similar shift in treatment strategy was driven by the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Prior to 2013, the Adult Treatment Panel III (ATP III) guidelines recommended a treat-to-target approach to achieve a target low-density lipoprotein (LDL) cholesterol goal based on coronary heart disease risk category (low, intermediate, and high). The 2013 ACC/AHA guideline moved away from cholesterol management based on LDL treatment targets to recommend fixed-dose statin therapy, with dose intensity determined by patient risk. This change, along with lowering the 10-year risk threshold to initiate statins for primary prevention of ASCVD to 7.5%, had a significant impact on cholesterol management in primary care. Clinicians previously had prescribed statins on the basis of LDL levels and now had to reframe their approach to management of ASCVD risk beyond just the LDL level. This resulted in many patients meeting guideline indications for statins for primary prevention, or having new recommendations for statin intensification, with what previously were considered LDL levels "at goal."
Working Toward Improving Outcomes
As PCPs work to change their approach to diabetes management and adapt to the new treatment paradigm, there is a great opportunity to improve cardiovascular and renal outcomes in patients with T2D. Although only about 12%-14% of patients eligible for SGLT2 inhibitors or GLP-1 receptor agonists receive guideline-indicated treatment, PCPs account for more of those prescriptions than other specialists. In 2023, the Standards of Care in Diabetes expanded the heart failure indication for SGLT2 inhibitors to include both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. Additionally, GLP-1 receptor agonists are now preferred to insulin therapy in the absence of symptomatic hyperglycemia or evidence of ongoing catabolism. The preference for GLP-1 receptor agonists minimizes hypoglycemia risk and reflects an enhanced focus on weight loss as a critical component of diabetes treatment. Weight loss greater than 10% generates disease-modifying effects and may improve long-term cardiovascular outcomes.
Despite guideline-indicated recommendations for SGLT2 inhibitors and GLP-1 receptor agonists, gaps in insurance coverage and high out-of-pocket costs remain significant barriers to prescribing these drugs and to patient adherence. At present, generic formulations of SGLT2 inhibitors and GLP-1 receptor agonists are not available. However, generic versions of liraglutide and dapagliflozin may be available in the next few years. Until then, clinicians and patients will continue to rely on drug savings cards and discount programs through pharmaceutical companies.
By working smarter, PCPs can help patients broaden their view of diabetes management beyond their A1c level to the prevention and treatment of diabetes complications. At the healthcare provider level, we can help patients with T2D meet weight loss goals by prescribing guideline-indicated GLP-1 receptor agonists irrespective of glycemic control. As we prescribe statins for secondary prevention of cardiovascular disease, we can harness the mortality benefits of SGLT2 inhibitors and GLP-1 receptor agonists that can help patients live longer. As we review guideline-directed medical therapy in patients with heart failure, there is an opportunity to add SGLT2 inhibitors to the patient's heart failure regimen in an effort to keep them out of the hospital. In so doing, we can help patients with T2D live longer, prevent cardiovascular events, and delay or prevent the progression of chronic kidney disease.
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Cite this: A New Approach to Type 2 Diabetes Management in Primary Care - Medscape - Mar 28, 2023.